Trotz umfangreicher Studien zum Morbus Huntington (M. H.) gibt es bei dieser Krankheit nach wie v... more Trotz umfangreicher Studien zum Morbus Huntington (M. H.) gibt es bei dieser Krankheit nach wie vor zahlreiche unge16ste Fragen. So bereitet die Friiherkennung bei bekannter Familienanamnese dieses autosomal dominanten Erbleidens sowie die Differentialdiagnose bei unbekannter famiWirer Belastung erhebliche Schwierigkeiten. Fehldiagnosen sind im Anfangsstadium und bei leerer Familienanamnese haufig, da es bis heute weder einen psychometrischen noch neurologischen, noch genetischen beweisenden Test gibt. Eines der Ziele des interdisziplinaren Chorea-Forschungs-und-Beratungszentrums der Universitat Dusseldorf war es daher, Routineverfahren der neurologischen sowie der psychologischen Diagnostik auf ihre Anwendbarkeit bei der Friih-und Differentialdiagnose des M. H. zu priifen. Dariiber hinaus sollten Untersuchungen des Himstoffwechsels Anhaltspunkte fUr mogliche pathogenetische Mechanismen liefem. An dieser Stelle sollen die bei choreatischen Huntington-Patienten erhobenen Befunde mitgeteilt werden. Uber die Wertigkeit der Untersuchungen bei Risikopersonen wird an anderer Stelle berichtet. Patienten Vom Chorea-Forschungs-und-Beratungszentrum wurden seit 198155 Choreatiker mit gesicherter Familienanamnese untersucht und beraten. Das Lebensalter betrug 21-70 Jahre, das Manifestationsalter, bezogen auf die neurologische Symptomatik, 18-58 Jahre, die Choreadauer 1-26 Jahre. AIle Patienten zeigten choreatische Hyperkinesen, deren Auspragung von einem der Autoren nach klinischem Eindruck von leicht (1) bis schwer (3) skaliert wurde (vgl. Tabelle 1). Der Grad der Behinderung durch den M. H. wurde anhand der Tabelle 2 vorgenommen. Die Einstufungen beruhen auf eigenen Untersuchungen und auf Angaben der Familienangehorigen.
Background In his classical paper, George Huntington described movement disorder and psychiatric ... more Background In his classical paper, George Huntington described movement disorder and psychiatric symptoms. In 1915, Davenport described ‘a biotype in which the tremors are absent but mental deterioration present’. In 1921, Entres used the term ‘chorea sine chorea’ to depict onset of HD without motor symptoms. Until today diagnosis of HD without overt motor symptoms is an unmet need. Aims Present corroborated data on age at onset and onset of clinical symptoms (motor, cognitive, behavioral) as available form charts of patient seen at the GHI out-patient clinic. Methods/techniques SPSS analysis of age at onset of symptoms of 260 symptomatic HD patients (DCL=4) available for analysis at GHI before December 2017. Results/outcome In those 260 patients both age at diagnosis and at onset of motor symptoms was documented. In 10 patients of this group, HD was diagnosed in an external center before documented motor onset. In 9 of these cases, diagnosis was established within 1 year after motor onset. Depression was documented in 196 of the 260 patients. Depression was present in 32% before the onset of motor symptoms and was the symptom that appeared more frequently before motor symptoms than any other symptom. Cognitive problems were documented in 211 cases, but occurred in only 15% before the onset of motor symptoms. Conclusion New guidelines are needed to enable clinicians to provide adequate care early and establish a reliable diagnosis of HD in the absence of overt motor symptoms, permitting access to health care support.
Background: Assessment of motor symptoms in Huntington's disease (HD) is based on the Unified-HD-... more Background: Assessment of motor symptoms in Huntington's disease (HD) is based on the Unified-HD-Rating-Scale-Total-Motor-Score (UHDRS-TMS). Its categorical and rater-dependent nature reduces the ability to detect subtle changes and often placebo effects have been observed in trials. We have previously shown that impairments in isometric force matching can be detected by quantitative motor (Q-Motor) assessments of tongue protrusion forces (glossomotography) in HD. Objective: We aimed to investigate whether similar impairments in isometric force matching can be detected in tasks assessing hand and foot force coordination and whether correlations with clinical measures and the disease burden score can be found. Methods: Using a pre-calibrated force transducer, the ability of subjects to generate and maintain isometric forces at different target levels displayed on a monitor was assessed. Target forces applied in the hand were 1.5 and 5 Newton [N] and in feet 1, 5, and 10 N. Subjects with HD (n = 31) and age-matched controls (n = 22) were recruited from the HD outpatient clinic. Results: All paradigms distinguished controls from HD. The static coefficient of variability (%) was the most robust measure across all matching tasks. Correlations with clinical measures, such as the UHDRS-TMS, TFC, and the DBS were found. Conclusions: Assessment of hand and foot force matching tasks was feasible and provided quantitative objective measures for severity of motor phenotype in HD. Since both upper and lower extremity motor function are relevant for everyday activities, these measures should be further assessed as candidates for developing functionally meaningful quantitative motor tasks.
Objective: A systematic review examining the presence and nature of language disorders associated... more Objective: A systematic review examining the presence and nature of language disorders associated with Huntington disease (HD). Background: HD is characterized by gradual motor dysfunction, psychiatric problems, and cognitive decline. Communication abilities in HD may be affected not only by dysarthria but also by language impairment. However, the nature and type of this impairment is not well defined. Methods: We searched the PubMed and PsycINFO databases and selected studies on the basis of the original language of the article, peer-review status, and specificity of the results regarding language and communication disorders. Results: Thirty-one articles meeting the selection criteria were selected for this review. According to most of the studies, individuals with HD present with primary deficits of language. However, a few authors suggested that language deficits in HD result from nonlinguistic impairments, or that language abilities are largely preserved. More specifically, studies showed that HD is associated with difficulties in producing and understanding sentences and discourse, processing semantic representations of object and action concepts, retrieving lexical forms of nouns, and applying morphological and syntactic rules. There is some disagreement regarding whether HD affects reading abilities, sentence production, semantic processing, and application of morphological rules in verb conjugation. Conclusions: Although people with HD present with language impairment, further studies are needed to identify their functional origin. Clinical studies are also needed to determine the impact of such impairments on an individual’s functional communication in daily living and to chart the progression of the impairments over the course of the disease.
Journal of Neurology, Neurosurgery & Psychiatry, 2010
Background Objective assessment of balance control in dynamic posturography (DP) may be helpful t... more Background Objective assessment of balance control in dynamic posturography (DP) may be helpful to assess motor phenotype in premanifest (pHD) and symptomatic (sHD) Huntington's disease (HD). HD patients are known to develop a decline of balance that results in a high risk of falls. Aim To investigate whether DP using a mobile platform (one degree of freedom, anterior-posterior) is able to detect a motor phenotype in pHD and sHD and to assess whether these measures correlate to the severity of disease as assessed by the UHDRS-TMS, DBS (Disease Burden Score), CS (Cognitive Score), FAS (Functional Assessment Score) and TFC (Total Functional Capacity). Methods 32 HD patients (pHD=11, sHD=21) and 20 age-and-sex-matched controls stood on a mobile platform on a force plate for 25 s, (outcome measures were surface (S), velocity (V) and distance (D) of the center of mass movement). Patients were assessed by the UHDRS-TMS, DBS, CS, FAS and TFC. Non-parametric statistics were performed to compare patients and controls (Mann-Whitney-Test) and to assess dependent variables (Wilcoxon-Test) using SAS 9.2. Correlation analysis was performed using non-parametric Spearman correlations. Results DP measures were significantly increased in pHD subjects compared to controls (S: p<0.025, V: p<0.009 and D: p<0.006) in contrast to no significant increase observed in static posturography (S: p<0.226, V: p<0.334 and D: p<0.349). In sHD, measures were significantly increased (p<0.0001). Across all HD subjects DP measures S(r=0.647***), V(r=0.577***) and D(r=0.542***) were correlated to the severity of the disease as assessed in the UHDRS-TMS, DBS (r≥0.475**), CS (r≥−0.376*), FAS (r≥−0.456**) and TFC (r≥−0.416**). Conclusion Assessment of balance in DP is more sensitive in pHD than static measures and provides objective and quantitative readouts. The DP measures correlated to the severity of the motor phenotype assessed in the UHDRS-TMS, DBS, CS, FAS and TFC.
Journal of Neurology, Neurosurgery & Psychiatry, 2010
Background With the complexity of symptoms of Huntington's disease (HD), its neurological and... more Background With the complexity of symptoms of Huntington's disease (HD), its neurological and mental impairments, it is quite difficult to measure the effects of rehabilitative treatment. As part of our day care rehabilitation programme, we have pursued the question of whether the motor and cognitive scales of the Unified Huntington's Disease Rating Scale (UHDRS) and other scales used in the REGISTRY Study can be used to detect the effects of rehabilitation of HD patients. Methods and patients By April 2010, 23 HD patients (10 women, 13 men) completed the rehabilitation programme. In one patient the final evaluation could not be performed due to organisational reasons, and one patient died of pneumonia before the end of rehabilitation (she also suffered from kidney and heart failure). At the beginning and on completion of rehabilitation, Huntington's patients are examined with the tests of the REGISTRY study. To capture mood changes, we used the Beck Depression Inventory and Hamilton Depression Scale, the competence in daily living was scored with TFC, Function Score and Independence Scale. Results The basic data are presented in table 1 and the changes after rehabilitation in table 2. We were able to show positive effects on motor function and cognitive performance; there was a tendency to improved mood in the self-report questionnaire BDI. No treatment benefit could be achieved when the mood of the patient worsened - usually caused by a lack of funding for continuation of the therapy or if institutionalisation of the patient was unavoidable. Table 1 Baseline data Variable n Min Max Mean SD CAG_HD 23 37 54 44.96 4.2 CAG_N 21 14 25 17.86 2.4 Age (a) 23 32.6 68.8 47.24 11.0 Age of onset (a) 23 19 58 35.96 12.2 Duration of HD (months) 23 30 427 128.04 87.2 Duration of rehabilitation (days) 21 17 73 39.29 17.0 Table 2 Changes after rehabilitation Test (range – normal in bold) n Min Max Median Mean±SD Paired differ (mean±SEM) p Value UHDRS Motor (0–124 points) (Start) 23 8 70 32.0 36.5±18.3 −6.1±1.9 ***0.004 (Start) 21 0 60 29.0 38.1±18.3 (End) 21 32.0±16.8 UHDRS Cognitive (>200–0 points) (Start) 22 76 283 151.0 165.7±51.1 7.9±3.5 *0.035 (Start) 21 92 294 160.0 163.3±51.1 (End) 21 171.1±53.9 BDI (0–63 points) (Start) 23 1 47 9.0 12.6±13.0 −5.0±2.5 (*)0.054 (Start) 20 2 27 4.5 12.0±12.5 (End) 20 7.0±7.1 HDS (0–65 points) (Start) 23 2 20 7.0 8.4±5.2 −0.5±0.9 0.56 (Start) 21 0 26 6.0 8.5±5.5 (End) 21 8.0±6.1 Indep Score (100–0 points) (Start) 23 60 100 80.0 76.7±9.0 −1.43±0.93 0.137 (Start) 21 60 100 75.0 76.4±9.4 (End) 21 75.0±10.0 Function score (25–0 points) (Start) 23 8 25 19.0 18.3±5.0 −0.0±0.4 1.0 (Start) 21 9 25 18.0 18.0±5.1 (End) 21 18.0±4.9 TFC (13–0 Points) (Start) 23 2 13 7.0 7.4±3.3 −0.29±0.38 0.452 (Start) 21 2 13 5.0 7.2±3.4 (End) 21 6.9±3.3 Paired differ, paired difference t test; p, statistical significance. BDI, Beck Depression Inventory; HDS, Hamilton Depression Score; Indep Score, Independence Score; TFC, total functional capacity; UHDRS, Unified Huntington's Disease Rating Scale. Conclusions Motor and cognitive UHDRS scales and the other scales used in the REGISTRY are suitable to quantify the changes in the course of a rehabilitation programme. Significant positive effects of an adequate rehabilitation programme for HD patients on motor function, cognition and mood could thus be demonstrated.
Journal of Neurology, Neurosurgery & Psychiatry, 2010
Background Patients with Huntington's disease (HD) develop a progressive impairment of stabil... more Background Patients with Huntington's disease (HD) develop a progressive impairment of stability of stance and walking (Rumpf et al. 2007), frequently resulting in falls and injuries. Objective assessment of postural control in HD may be helpful to assess the risk of injury and may serve as a surrogate marker for motor phenotype dysfunction. Objective To investigate whether HD patients exhibit impairments in balance control that can be assessed by the BBS and whether the BBS correlates to the severity of disease as assessed by the UHDRS-TMS and quantitative measures of balance recorded by a force plate (posturography). Methods HD patients (n=48: 11 premanifest, 37 symptomatic HD) and age-and-sex-matched controls (n=20) were assessed by the Berg Balance Scale (BBS), the UHDRS-TMS and a force plate (standing still with eyes open and closed for 25 s). Stability of center of mass (COM) location was assessed by the variables SURFACE, VELOCITY and DISTANCE. Non-parametric statistics were performed to compare patients and controls (Mann-Whitney-Test) and to assess dependent variables (Wilcoxon-Test) using SAS 9.2. Correlation analysis was performed using non-parametric Spearman correlations. Results The BBS correlated in all HD gene-carriers to the UHDRS-TMS with r=−0.786 in symptomatic patients the correlation was r=−0.826. In symptomatic patients BBS correlated with force plate measures SURFACE (r≥−0.665), VELOCITY (r≥−0.453) and DISTANCE (r≥−0.465). However, BBS was insensitive to impairments of balance in patients with UHDRS-TMS ≤20. Force plate measures were significantly increased in HD compared to controls (p<0.001). All variables correlated to the severity of the disease as assessed in the UHDRS-TMS (r≥0.705). Conclusions Assessment of balance with the BBS is limited to patients with UHDRS-TMS scores ≥20. In contrast, objective and quantitative force plate measures are more sensitive covering a wider range of disease.
Electroencephalography and Clinical Neurophysiology, 1986
Event-related potentials (ERPs) were studied in patients with Huntington&amp;amp;#39;s diseas... more Event-related potentials (ERPs) were studied in patients with Huntington&amp;amp;#39;s disease (HD) and their offspring at risk in a simple auditory oddball paradigm requiring the counting of the rarer of two stimulus categories. Group statistical analysis revealed prolongation of latencies of components P2, N2 and especially P3 in HD patients and to a lesser extent in at-risks. In a large population of normals the age-latency relationship for component P3 showed a non-linear shape with increasing slope and scatter in the older age groups. A bipartate linear regression analysis splitting the normal population at age 50 was used for detection of abnormalities of P3 latency in individual cases. Abnormal P3 latencies were present in the majority of HD patients and also in 25% of clinically normal at-risks. Correlation analysis of ERP components with detailed psychometry revealed a particularly high association of P3 latencies with measurements requiring speeded information processing in non-verbal tasks. P3 amplitude did not covary with performance scores but unlike P3 latency showed association with depression and psychosis scores. From the results it appears that analysis of ERPs is a useful electrophysiological tool for an objective assessment of cognition both in clinically definite and subclinical stages.
Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section, 1984
Abnormalities of somatosensory evoked potentials (SEPs) in patients with Huntington's disease wer... more Abnormalities of somatosensory evoked potentials (SEPs) in patients with Huntington's disease were first described by Takahashi and Okada (1972), who observed prolonged latencies and reduced amplitudes of the early cortical SEP components in 4 patients. Oepen et al. (1981, 1982) investigated 13 patients and also found a reduction in the amplitude of the early components. Josiassen et al. (1982) were the first to investigate a larger sample of 21 patients with Huntington's disease. They found a drastic diminution of the amplitudes of the early cortical responses to median nerve stimulation and an increase in latency. These changes were seen in the majority of the patients tested, but also in some of the subjects at risk. The study presented here was undertaken to answer the following questions: (1) Which is the most reliable pathological parameter of the cortical median SEPs in Huntington's disease? (2) Is it useful to stimulate the tibial nerve to get more information in patients with ambiguous median SEPs? By recording the cervical potentials during stimulation of the tibial nerve additional information is obtained about possible involvement of the dorsal column. (3) Are there any alterations of the SEPs in clinically unaffected offspring of first order, who are carriers of the pathological gene? Some patients with symptomatic chorea were included in the study to test the method for its value in the differential diagnosis of Huntington's disease. A short account of these results has been published elesewhere (Engel et al. 1982; Noth et al. 1983).
Verhandlungen der Deutschen Gesellschaft für Neurologie, 1995
Eine Degeneration des Striatums liegt einer Vielzahl unterschiedlicher extrapyrami-dalmotorischer... more Eine Degeneration des Striatums liegt einer Vielzahl unterschiedlicher extrapyrami-dalmotorischer Erkrankungen zugrunde. Deshalb ist die fruhzeitige Erkennung derartiger Veranderungen, wie sie beispielsweise positronenemissionstomographisch durch den Nachweis eines reduzierten Striatalen Glukoseverbrauchs (rCMRGlc) moglich ist, von klinischer Bedeutung. Im Rahmen der Diagnostik des Morbus Huntington (HD), welcher hier exemplarisch behandelt wird, gelingt mit Hilfe der Positronenemissionstomographie (PET) der fruhzeitige Nachweis einer beginnenden Striatalen Dysfunktion (Mazziotta et al. 1987; Hayden et al. 1987; Kuwert et al. 1993). Neuerdings erreichen moderne hochauflosende Drei-Kopf-SPECT-Systeme bei geringeren Kosten und insgesamt besserer Verfugbarkeit beinahe die Abbildungsqualitat der PET. Das Ziel dieser Studie war es, die diagnostische Wertigkeit der SPECT mit [99mTC]-hexamethylpropyleneamine oxime (HMPAO) im Vergleich zur PET mit 18F-Fluorodeoxyglukose (FDG) bei Patienten mit HD zu evaluieren.
Radioactive Isotopes in Clinical Medicine and Research, 1995
The aim of this study was to compare the performance of (Tc-99m) HMPAO-SPECT with that of FDG-PET... more The aim of this study was to compare the performance of (Tc-99m) HMPAO-SPECT with that of FDG-PET in the detection of striatal degeneration as it occurs in Huntington’s disease (HD).
Trotz umfangreicher Studien zum Morbus Huntington (M. H.) gibt es bei dieser Krankheit nach wie v... more Trotz umfangreicher Studien zum Morbus Huntington (M. H.) gibt es bei dieser Krankheit nach wie vor zahlreiche unge16ste Fragen. So bereitet die Friiherkennung bei bekannter Familienanamnese dieses autosomal dominanten Erbleidens sowie die Differentialdiagnose bei unbekannter famiWirer Belastung erhebliche Schwierigkeiten. Fehldiagnosen sind im Anfangsstadium und bei leerer Familienanamnese haufig, da es bis heute weder einen psychometrischen noch neurologischen, noch genetischen beweisenden Test gibt. Eines der Ziele des interdisziplinaren Chorea-Forschungs-und-Beratungszentrums der Universitat Dusseldorf war es daher, Routineverfahren der neurologischen sowie der psychologischen Diagnostik auf ihre Anwendbarkeit bei der Friih-und Differentialdiagnose des M. H. zu priifen. Dariiber hinaus sollten Untersuchungen des Himstoffwechsels Anhaltspunkte fUr mogliche pathogenetische Mechanismen liefem. An dieser Stelle sollen die bei choreatischen Huntington-Patienten erhobenen Befunde mitgeteilt werden. Uber die Wertigkeit der Untersuchungen bei Risikopersonen wird an anderer Stelle berichtet. Patienten Vom Chorea-Forschungs-und-Beratungszentrum wurden seit 198155 Choreatiker mit gesicherter Familienanamnese untersucht und beraten. Das Lebensalter betrug 21-70 Jahre, das Manifestationsalter, bezogen auf die neurologische Symptomatik, 18-58 Jahre, die Choreadauer 1-26 Jahre. AIle Patienten zeigten choreatische Hyperkinesen, deren Auspragung von einem der Autoren nach klinischem Eindruck von leicht (1) bis schwer (3) skaliert wurde (vgl. Tabelle 1). Der Grad der Behinderung durch den M. H. wurde anhand der Tabelle 2 vorgenommen. Die Einstufungen beruhen auf eigenen Untersuchungen und auf Angaben der Familienangehorigen.
Background In his classical paper, George Huntington described movement disorder and psychiatric ... more Background In his classical paper, George Huntington described movement disorder and psychiatric symptoms. In 1915, Davenport described ‘a biotype in which the tremors are absent but mental deterioration present’. In 1921, Entres used the term ‘chorea sine chorea’ to depict onset of HD without motor symptoms. Until today diagnosis of HD without overt motor symptoms is an unmet need. Aims Present corroborated data on age at onset and onset of clinical symptoms (motor, cognitive, behavioral) as available form charts of patient seen at the GHI out-patient clinic. Methods/techniques SPSS analysis of age at onset of symptoms of 260 symptomatic HD patients (DCL=4) available for analysis at GHI before December 2017. Results/outcome In those 260 patients both age at diagnosis and at onset of motor symptoms was documented. In 10 patients of this group, HD was diagnosed in an external center before documented motor onset. In 9 of these cases, diagnosis was established within 1 year after motor onset. Depression was documented in 196 of the 260 patients. Depression was present in 32% before the onset of motor symptoms and was the symptom that appeared more frequently before motor symptoms than any other symptom. Cognitive problems were documented in 211 cases, but occurred in only 15% before the onset of motor symptoms. Conclusion New guidelines are needed to enable clinicians to provide adequate care early and establish a reliable diagnosis of HD in the absence of overt motor symptoms, permitting access to health care support.
Background: Assessment of motor symptoms in Huntington's disease (HD) is based on the Unified-HD-... more Background: Assessment of motor symptoms in Huntington's disease (HD) is based on the Unified-HD-Rating-Scale-Total-Motor-Score (UHDRS-TMS). Its categorical and rater-dependent nature reduces the ability to detect subtle changes and often placebo effects have been observed in trials. We have previously shown that impairments in isometric force matching can be detected by quantitative motor (Q-Motor) assessments of tongue protrusion forces (glossomotography) in HD. Objective: We aimed to investigate whether similar impairments in isometric force matching can be detected in tasks assessing hand and foot force coordination and whether correlations with clinical measures and the disease burden score can be found. Methods: Using a pre-calibrated force transducer, the ability of subjects to generate and maintain isometric forces at different target levels displayed on a monitor was assessed. Target forces applied in the hand were 1.5 and 5 Newton [N] and in feet 1, 5, and 10 N. Subjects with HD (n = 31) and age-matched controls (n = 22) were recruited from the HD outpatient clinic. Results: All paradigms distinguished controls from HD. The static coefficient of variability (%) was the most robust measure across all matching tasks. Correlations with clinical measures, such as the UHDRS-TMS, TFC, and the DBS were found. Conclusions: Assessment of hand and foot force matching tasks was feasible and provided quantitative objective measures for severity of motor phenotype in HD. Since both upper and lower extremity motor function are relevant for everyday activities, these measures should be further assessed as candidates for developing functionally meaningful quantitative motor tasks.
Objective: A systematic review examining the presence and nature of language disorders associated... more Objective: A systematic review examining the presence and nature of language disorders associated with Huntington disease (HD). Background: HD is characterized by gradual motor dysfunction, psychiatric problems, and cognitive decline. Communication abilities in HD may be affected not only by dysarthria but also by language impairment. However, the nature and type of this impairment is not well defined. Methods: We searched the PubMed and PsycINFO databases and selected studies on the basis of the original language of the article, peer-review status, and specificity of the results regarding language and communication disorders. Results: Thirty-one articles meeting the selection criteria were selected for this review. According to most of the studies, individuals with HD present with primary deficits of language. However, a few authors suggested that language deficits in HD result from nonlinguistic impairments, or that language abilities are largely preserved. More specifically, studies showed that HD is associated with difficulties in producing and understanding sentences and discourse, processing semantic representations of object and action concepts, retrieving lexical forms of nouns, and applying morphological and syntactic rules. There is some disagreement regarding whether HD affects reading abilities, sentence production, semantic processing, and application of morphological rules in verb conjugation. Conclusions: Although people with HD present with language impairment, further studies are needed to identify their functional origin. Clinical studies are also needed to determine the impact of such impairments on an individual’s functional communication in daily living and to chart the progression of the impairments over the course of the disease.
Journal of Neurology, Neurosurgery & Psychiatry, 2010
Background Objective assessment of balance control in dynamic posturography (DP) may be helpful t... more Background Objective assessment of balance control in dynamic posturography (DP) may be helpful to assess motor phenotype in premanifest (pHD) and symptomatic (sHD) Huntington's disease (HD). HD patients are known to develop a decline of balance that results in a high risk of falls. Aim To investigate whether DP using a mobile platform (one degree of freedom, anterior-posterior) is able to detect a motor phenotype in pHD and sHD and to assess whether these measures correlate to the severity of disease as assessed by the UHDRS-TMS, DBS (Disease Burden Score), CS (Cognitive Score), FAS (Functional Assessment Score) and TFC (Total Functional Capacity). Methods 32 HD patients (pHD=11, sHD=21) and 20 age-and-sex-matched controls stood on a mobile platform on a force plate for 25 s, (outcome measures were surface (S), velocity (V) and distance (D) of the center of mass movement). Patients were assessed by the UHDRS-TMS, DBS, CS, FAS and TFC. Non-parametric statistics were performed to compare patients and controls (Mann-Whitney-Test) and to assess dependent variables (Wilcoxon-Test) using SAS 9.2. Correlation analysis was performed using non-parametric Spearman correlations. Results DP measures were significantly increased in pHD subjects compared to controls (S: p<0.025, V: p<0.009 and D: p<0.006) in contrast to no significant increase observed in static posturography (S: p<0.226, V: p<0.334 and D: p<0.349). In sHD, measures were significantly increased (p<0.0001). Across all HD subjects DP measures S(r=0.647***), V(r=0.577***) and D(r=0.542***) were correlated to the severity of the disease as assessed in the UHDRS-TMS, DBS (r≥0.475**), CS (r≥−0.376*), FAS (r≥−0.456**) and TFC (r≥−0.416**). Conclusion Assessment of balance in DP is more sensitive in pHD than static measures and provides objective and quantitative readouts. The DP measures correlated to the severity of the motor phenotype assessed in the UHDRS-TMS, DBS, CS, FAS and TFC.
Journal of Neurology, Neurosurgery & Psychiatry, 2010
Background With the complexity of symptoms of Huntington's disease (HD), its neurological and... more Background With the complexity of symptoms of Huntington's disease (HD), its neurological and mental impairments, it is quite difficult to measure the effects of rehabilitative treatment. As part of our day care rehabilitation programme, we have pursued the question of whether the motor and cognitive scales of the Unified Huntington's Disease Rating Scale (UHDRS) and other scales used in the REGISTRY Study can be used to detect the effects of rehabilitation of HD patients. Methods and patients By April 2010, 23 HD patients (10 women, 13 men) completed the rehabilitation programme. In one patient the final evaluation could not be performed due to organisational reasons, and one patient died of pneumonia before the end of rehabilitation (she also suffered from kidney and heart failure). At the beginning and on completion of rehabilitation, Huntington's patients are examined with the tests of the REGISTRY study. To capture mood changes, we used the Beck Depression Inventory and Hamilton Depression Scale, the competence in daily living was scored with TFC, Function Score and Independence Scale. Results The basic data are presented in table 1 and the changes after rehabilitation in table 2. We were able to show positive effects on motor function and cognitive performance; there was a tendency to improved mood in the self-report questionnaire BDI. No treatment benefit could be achieved when the mood of the patient worsened - usually caused by a lack of funding for continuation of the therapy or if institutionalisation of the patient was unavoidable. Table 1 Baseline data Variable n Min Max Mean SD CAG_HD 23 37 54 44.96 4.2 CAG_N 21 14 25 17.86 2.4 Age (a) 23 32.6 68.8 47.24 11.0 Age of onset (a) 23 19 58 35.96 12.2 Duration of HD (months) 23 30 427 128.04 87.2 Duration of rehabilitation (days) 21 17 73 39.29 17.0 Table 2 Changes after rehabilitation Test (range – normal in bold) n Min Max Median Mean±SD Paired differ (mean±SEM) p Value UHDRS Motor (0–124 points) (Start) 23 8 70 32.0 36.5±18.3 −6.1±1.9 ***0.004 (Start) 21 0 60 29.0 38.1±18.3 (End) 21 32.0±16.8 UHDRS Cognitive (>200–0 points) (Start) 22 76 283 151.0 165.7±51.1 7.9±3.5 *0.035 (Start) 21 92 294 160.0 163.3±51.1 (End) 21 171.1±53.9 BDI (0–63 points) (Start) 23 1 47 9.0 12.6±13.0 −5.0±2.5 (*)0.054 (Start) 20 2 27 4.5 12.0±12.5 (End) 20 7.0±7.1 HDS (0–65 points) (Start) 23 2 20 7.0 8.4±5.2 −0.5±0.9 0.56 (Start) 21 0 26 6.0 8.5±5.5 (End) 21 8.0±6.1 Indep Score (100–0 points) (Start) 23 60 100 80.0 76.7±9.0 −1.43±0.93 0.137 (Start) 21 60 100 75.0 76.4±9.4 (End) 21 75.0±10.0 Function score (25–0 points) (Start) 23 8 25 19.0 18.3±5.0 −0.0±0.4 1.0 (Start) 21 9 25 18.0 18.0±5.1 (End) 21 18.0±4.9 TFC (13–0 Points) (Start) 23 2 13 7.0 7.4±3.3 −0.29±0.38 0.452 (Start) 21 2 13 5.0 7.2±3.4 (End) 21 6.9±3.3 Paired differ, paired difference t test; p, statistical significance. BDI, Beck Depression Inventory; HDS, Hamilton Depression Score; Indep Score, Independence Score; TFC, total functional capacity; UHDRS, Unified Huntington's Disease Rating Scale. Conclusions Motor and cognitive UHDRS scales and the other scales used in the REGISTRY are suitable to quantify the changes in the course of a rehabilitation programme. Significant positive effects of an adequate rehabilitation programme for HD patients on motor function, cognition and mood could thus be demonstrated.
Journal of Neurology, Neurosurgery & Psychiatry, 2010
Background Patients with Huntington's disease (HD) develop a progressive impairment of stabil... more Background Patients with Huntington's disease (HD) develop a progressive impairment of stability of stance and walking (Rumpf et al. 2007), frequently resulting in falls and injuries. Objective assessment of postural control in HD may be helpful to assess the risk of injury and may serve as a surrogate marker for motor phenotype dysfunction. Objective To investigate whether HD patients exhibit impairments in balance control that can be assessed by the BBS and whether the BBS correlates to the severity of disease as assessed by the UHDRS-TMS and quantitative measures of balance recorded by a force plate (posturography). Methods HD patients (n=48: 11 premanifest, 37 symptomatic HD) and age-and-sex-matched controls (n=20) were assessed by the Berg Balance Scale (BBS), the UHDRS-TMS and a force plate (standing still with eyes open and closed for 25 s). Stability of center of mass (COM) location was assessed by the variables SURFACE, VELOCITY and DISTANCE. Non-parametric statistics were performed to compare patients and controls (Mann-Whitney-Test) and to assess dependent variables (Wilcoxon-Test) using SAS 9.2. Correlation analysis was performed using non-parametric Spearman correlations. Results The BBS correlated in all HD gene-carriers to the UHDRS-TMS with r=−0.786 in symptomatic patients the correlation was r=−0.826. In symptomatic patients BBS correlated with force plate measures SURFACE (r≥−0.665), VELOCITY (r≥−0.453) and DISTANCE (r≥−0.465). However, BBS was insensitive to impairments of balance in patients with UHDRS-TMS ≤20. Force plate measures were significantly increased in HD compared to controls (p<0.001). All variables correlated to the severity of the disease as assessed in the UHDRS-TMS (r≥0.705). Conclusions Assessment of balance with the BBS is limited to patients with UHDRS-TMS scores ≥20. In contrast, objective and quantitative force plate measures are more sensitive covering a wider range of disease.
Electroencephalography and Clinical Neurophysiology, 1986
Event-related potentials (ERPs) were studied in patients with Huntington&amp;amp;#39;s diseas... more Event-related potentials (ERPs) were studied in patients with Huntington&amp;amp;#39;s disease (HD) and their offspring at risk in a simple auditory oddball paradigm requiring the counting of the rarer of two stimulus categories. Group statistical analysis revealed prolongation of latencies of components P2, N2 and especially P3 in HD patients and to a lesser extent in at-risks. In a large population of normals the age-latency relationship for component P3 showed a non-linear shape with increasing slope and scatter in the older age groups. A bipartate linear regression analysis splitting the normal population at age 50 was used for detection of abnormalities of P3 latency in individual cases. Abnormal P3 latencies were present in the majority of HD patients and also in 25% of clinically normal at-risks. Correlation analysis of ERP components with detailed psychometry revealed a particularly high association of P3 latencies with measurements requiring speeded information processing in non-verbal tasks. P3 amplitude did not covary with performance scores but unlike P3 latency showed association with depression and psychosis scores. From the results it appears that analysis of ERPs is a useful electrophysiological tool for an objective assessment of cognition both in clinically definite and subclinical stages.
Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section, 1984
Abnormalities of somatosensory evoked potentials (SEPs) in patients with Huntington's disease wer... more Abnormalities of somatosensory evoked potentials (SEPs) in patients with Huntington's disease were first described by Takahashi and Okada (1972), who observed prolonged latencies and reduced amplitudes of the early cortical SEP components in 4 patients. Oepen et al. (1981, 1982) investigated 13 patients and also found a reduction in the amplitude of the early components. Josiassen et al. (1982) were the first to investigate a larger sample of 21 patients with Huntington's disease. They found a drastic diminution of the amplitudes of the early cortical responses to median nerve stimulation and an increase in latency. These changes were seen in the majority of the patients tested, but also in some of the subjects at risk. The study presented here was undertaken to answer the following questions: (1) Which is the most reliable pathological parameter of the cortical median SEPs in Huntington's disease? (2) Is it useful to stimulate the tibial nerve to get more information in patients with ambiguous median SEPs? By recording the cervical potentials during stimulation of the tibial nerve additional information is obtained about possible involvement of the dorsal column. (3) Are there any alterations of the SEPs in clinically unaffected offspring of first order, who are carriers of the pathological gene? Some patients with symptomatic chorea were included in the study to test the method for its value in the differential diagnosis of Huntington's disease. A short account of these results has been published elesewhere (Engel et al. 1982; Noth et al. 1983).
Verhandlungen der Deutschen Gesellschaft für Neurologie, 1995
Eine Degeneration des Striatums liegt einer Vielzahl unterschiedlicher extrapyrami-dalmotorischer... more Eine Degeneration des Striatums liegt einer Vielzahl unterschiedlicher extrapyrami-dalmotorischer Erkrankungen zugrunde. Deshalb ist die fruhzeitige Erkennung derartiger Veranderungen, wie sie beispielsweise positronenemissionstomographisch durch den Nachweis eines reduzierten Striatalen Glukoseverbrauchs (rCMRGlc) moglich ist, von klinischer Bedeutung. Im Rahmen der Diagnostik des Morbus Huntington (HD), welcher hier exemplarisch behandelt wird, gelingt mit Hilfe der Positronenemissionstomographie (PET) der fruhzeitige Nachweis einer beginnenden Striatalen Dysfunktion (Mazziotta et al. 1987; Hayden et al. 1987; Kuwert et al. 1993). Neuerdings erreichen moderne hochauflosende Drei-Kopf-SPECT-Systeme bei geringeren Kosten und insgesamt besserer Verfugbarkeit beinahe die Abbildungsqualitat der PET. Das Ziel dieser Studie war es, die diagnostische Wertigkeit der SPECT mit [99mTC]-hexamethylpropyleneamine oxime (HMPAO) im Vergleich zur PET mit 18F-Fluorodeoxyglukose (FDG) bei Patienten mit HD zu evaluieren.
Radioactive Isotopes in Clinical Medicine and Research, 1995
The aim of this study was to compare the performance of (Tc-99m) HMPAO-SPECT with that of FDG-PET... more The aim of this study was to compare the performance of (Tc-99m) HMPAO-SPECT with that of FDG-PET in the detection of striatal degeneration as it occurs in Huntington’s disease (HD).
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