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1.  Oral and dental health in Huntington‘s disease - an observational study 
BMC Neurology  2013;13:114.
Background
Only a few case reports and case series dealing with oral and dental health care are available in literature until now. The aim of the present pilot study was to determine the status of dental health in comparison to matched controls and to heighten the neurologists’ and dentists’ awareness of the oral aspects of the disease.
Methods
42 Huntington’s disease (HD) participants were scored according to the Unified Huntington’s Disease Rating Scale. The dental status was assessed by using the well established score for decayed, missing, and filled teeth (DMFT) and the dental plaque score (Silness-Loe plaque index).
Results
Compared to controls HD participants showed significantly more decayed teeth and more plaques in both plaque indices. A higher motor impairment and a lower functional status of the patients lead to a worsening in dental status.
Conclusion
Possible reasons for our findings are discussed. Apart from local oral complications general complications may also occur. Thus, as a consequence, we would encourage patients, caregivers, neurologists, and the dentists to ensure regular preventive dental examinations and dental treatments of individuals with Huntington’s disease even in the premanifest stage of this disease.
doi:10.1186/1471-2377-13-114
PMCID: PMC3766132  PMID: 24138900
2.  No evidence of impaired gastric emptying in early Huntington‘s Disease 
PLoS Currents  2011;3:RRN1284.
Background: Several factors, such as dysphagia, an increased motor activity, increased metabolic rate and a hypermetabolic state have been discussed as contributing to weight loss even at the early stages of Huntington’s Disease (HD). Aim of this pilot study was to investigate gastric emptying as a possible reason for weight loss in HD.
Methods: 11 HD participants at early stages of the disease and matched controls were investigated by using the well-established and non-invasive 13C-octanoate breath test. The “Gastroparesis Cardinal Symptom Index” and the “Short-Form Leeds Dyspepsia Questionnaire” were used for clinical evaluation of gastroparesis or dyspepsia.
Results: When compared to standard values ​​given in literature and controls all HD patients had normal breath test results. There was no evidence of gastroparesis or dyspepsia. There was a correlation of breath test results with the cognitive and functional performance of HD participants.
Conclusion: According to our data, there is no evidence of impaired gastric emptying in early HD. We can not exclude that gastric emptying contributes to weight loss at more advanced stages of the disease.
doi:10.1371/currents.RRN1284
PMCID: PMC3217813  PMID: 22130331
3.  Assessment of simple movements and progression of Huntington's disease 
Instrumental measurement of simple motion sequences reflects impairment in patients with Huntington's disease (HD). The objectives were to study the progress of symptoms of HD and tapping results in 42 patients with HD, without symptomatic drug treatment over 3 years. Assessment moments were at baseline, and at years 1, 2 and 3. Unified Huntington's Disease Rating Scale (UHDRS) total score and UHDRS arm score significantly increased. Motor test outcomes considerably worsened. Instrumental test results significantly correlated with both UHDRS scores at each assessment. Assessment of simple movement sequences is an additional simple method to follow impairment in patients with HD in addition to clinical rating.
doi:10.1136/jnnp.2006.105338
PMCID: PMC2077774  PMID: 17369593
4.  PGC-1alpha as modifier of onset age in Huntington disease 
Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In > 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modifying effects on the pathogenic process in HD.
doi:10.1186/1750-1326-4-10
PMCID: PMC2644307  PMID: 19200361
5.  Time Processing in Huntington's Disease: A Group-Control Study 
PLoS ONE  2007;2(12):e1263.
Background
“Timing” processes are mediated via a disturbed neuronal network including the basal ganglia. Brain structures important for “timing” are also discussed to be critical for the deterioration of movements in Huntington's disease (HD). Changes in “timing processes” are found in HD, but no study has varied the degree of motor demands in timing functions in parallel in HD. It may be hypothesized that timing functions may be deteriorated to a different extent in motor and non-motor timing, because in motor timing the underlying brain structures may be more demanding than in non-motor timing.
Methodology/Principle Findings
We assessed timing in two different experiments: a time-estimation (TE) and a time-discrimination (TD) task. The demand on motor functions is high in the TE-task and low in the TD-task. Furthermore, general motor ability was assessed at different complexity levels. A presymptomatic (pHD), a symptomatic (HD) and a control group were investigated. We found a decline in timing functions when demands on the motor system were high (TE-task), in HD and even in pHD, compared to controls. In non-motor timing (TD task) and in the assessment of general motor ability, performance in the pHD-group was comparable to the controls and better than in the symptomatic group. Performance in both timing tasks was related to the duration until the estimated age of onset in pHDs.
Conclusions/Significance
The study shows a selective deterioration of time-estimation processes in symptomatic and even presymptomatic Huntington's disease. Time-discrimination processes were not affected in both patient groups. The relation of timing performance to the duration until the estimated age of onset in pHD is of clinical importance.
doi:10.1371/journal.pone.0001263
PMCID: PMC2094403  PMID: 18060059
6.  Error Processing in Huntington's Disease 
PLoS ONE  2006;1(1):e86.
Background
Huntington's disease (HD) is a genetic disorder expressed by a degeneration of the basal ganglia inter alia accompanied with dopaminergic alterations. These dopaminergic alterations are related to genetic factors i.e., CAG-repeat expansion. The error (related) negativity (Ne/ERN), a cognitive event-related potential related to performance monitoring, is generated in the anterior cingulate cortex (ACC) and supposed to depend on the dopaminergic system. The Ne is reduced in Parkinson's Disease (PD). Due to a dopaminergic deficit in HD, a reduction of the Ne is also likely. Furthermore it is assumed that movement dysfunction emerges as a consequence of dysfunctional error-feedback processing. Since dopaminergic alterations are related to the CAG-repeat, a Ne reduction may furthermore also be related to the genetic disease load.
Methodology/Principle Findings
We assessed the error negativity (Ne) in a speeded reaction task under consideration of the underlying genetic abnormalities. HD patients showed a specific reduction in the Ne, which suggests impaired error processing in these patients. Furthermore, the Ne was closely related to CAG-repeat expansion.
Conclusions/Significance
The reduction of the Ne is likely to be an effect of the dopaminergic pathology. The result resembles findings in Parkinson's Disease. As such the Ne might be a measure for the integrity of striatal dopaminergic output function. The relation to the CAG-repeat expansion indicates that the Ne could serve as a gene-associated “cognitive” biomarker in HD.
doi:10.1371/journal.pone.0000086
PMCID: PMC1762335  PMID: 17183717
7.  No association between polymorphisms in the BDNF gene and age at onset in Huntington disease 
BMC Medical Genetics  2006;7:79.
Background
Recent evidence suggests that brain-derived neurotrophic factor (BDNF) is an attractive candidate for modifying age at onset (AO) in Huntington disease (HD). In particular, the functional Val66Met polymorphism appeared to exert a significant effect. Here we evaluate BDNF variability with respect to AO of HD using markers that represent the entire locus.
Methods
Five selected tagging polymorphisms were genotyped across a 65 kb region comprising the BDNF gene in a well established cohort of 250 unrelated German HD patients.
Results
Addition of BDNF genotype variations or one of the marker haplotypes to the effect of CAG repeat lengths did not affect the variance of the AO.
Conclusion
We were unable to verify a recently reported association between the functional Val66Met polymorphism in the BDNF gene and AO in HD. From our findings, we conclude that neither sequence variations in nor near the gene contribute significantly to the variance of AO.
doi:10.1186/1471-2350-7-79
PMCID: PMC1637098  PMID: 17096834
8.  Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR) polymorphisms on age at onset of Huntington disease 
Background
Huntington disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Recently, suggestive association has been reported between a single nucleotide polymorphism (SNP; rs1801131, also known as A1298C) in the methyltetrahydrofolate reductase (MTHFR) gene and AO of HD. 5,10-MTHFR is a key enzyme in the folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using part of a previously established study cohort plus additional patients and appropriate statistical methods, we reinvestigated two polymorphisms in the MTHFR gene, C677T and A1298C, as well as their association with AO in 167 HD patients.
Results
There was no statistically significant impact on AO for HD patients, neither of MTHFR SNPs nor of the combinations thereof.
Conclusion
Contrary to previously described evidence the A1298C polymorphism in the MTHFR gene does not appear to modulate AO of HD patients.
doi:10.1186/1477-5751-4-12
PMCID: PMC1327683  PMID: 16372906
9.  Age at onset of Huntington disease is not modulated by the R72P variation in TP53 and the R196K variation in the gene coding for the human caspase activated DNase (hCAD) 
BMC Medical Genetics  2005;6:35.
Background
TP53 is an attractive candidate for modifying age of onset (AO) in Huntington disease (HD): The amino-terminus of the mutated huntingtin (htt) exon 1 translation product has functional properties which may affect critically the TP53 pathway in HD neurons. The pathogenic domain of mutant htt interacts with nuclear transcription factors, and it potentially modulates TP53-induced transcriptional events. A single nucleotide polymorphism (SNP) resulting in the R72P exchange in TP53 protein might modulate the variation in AO. In addition, also the R196K replacement in human caspase activated DNase (hCAD) may theoretically affect the AO.
Methods
We have genotyped the polymorphisms R72P and R196K in a well established cohort of 167 unrelated HD patients.
Results
The expanded CAG repeat explained 30.8% of the variance in AO. Adding the genotypes of the SNPs investigated did not affect the variance of the AO variance explained.
Conclusion
In this replication study, no association was found explaining a significant amount of the variability in AO of HD thus contradicting a recent report.
doi:10.1186/1471-2350-6-35
PMCID: PMC1253512  PMID: 16202123
10.  Glutathione S-Transferase Ω 1 variation does not influence age at onset of Huntington's disease 
Background
Huntington's disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Circumstantial evidence suggests that additional features of the HD course are based on genetic traits. Therefore, it may be possible to investigate the genetic background of HD, i.e. to map the loci underlying the development and progression of the disease. Recently an association of Glutathione S-Transferase Ω 1 (GSTO1) and possibly of GSTO2 with AO was demonstrated for, both, Alzheimer's (AD) and Parkinson's disease (PD).
Methods
We have genotyped the polymorphisms rs4925 GSTO1 and rs2297235 GSTO2 in 232 patients with HD and 228 controls.
Results
After genotyping GSTO1 and GSTO2 polymorphisms, firstly there was no statistically significant difference in AO for HD patients, as well as secondly for HD patients vs. controls concerning, both, genotype and allele frequencies, respectively.
Conclusion
The GSTO1 and GSTO2 genes flanked by the investigated polymorphisms are not comprised in a primary candidate region influencing AO in HD.
doi:10.1186/1471-2350-5-7
PMCID: PMC394327  PMID: 15040808

Results 1-10 (10)