Biomedical subjects

N Quinn

Publications and source records attributed to N Quinn.

At least 19 recordsLinked to original sources

PubMed2006

Testing the validity of the PDQ-39 in patients with MSA.

We assessed the validity of the PDQ-39, a disease-specific health-related quality of life instrument for patients with Parkinson's disease, in patients with multiple system atrophy (MSA). Two hundred and seventy-nine patients completed the PDQ-39, the EQ-5D, the Hospital Anxiety and Depression Scale, and scales of life satisfaction and disease severity. Ceiling and floor effects were noted in some dimensions, and Mobility was skewed towards the severe end of the spectrum. Apart from the dimension of Social Support, all dimensions had high internal consistency. The factor structure of the PDQ-39 in MSA was stable, and convergent and divergent validity with other measures of quality of life and mental health were good. However, many of the specific features of MSA are not reflected in the PDQ-39. Higher order factor analysis did not support the use of a single summary index. We conclude that the PDQ-39 has only limited validity in patients with MSA.

Activities of Daily Living↗

PubMed2006

Severe tongue protrusion dystonia: clinical syndromes and possible treatment.

We describe intermittent or sustained severe involuntary tongue protrusion in patients with a dystonic syndrome. Speech, swallowing, and breathing difficulties can be severe enough to be life threatening. Causes include neuroacanthocytosis, pantothenate kinase-associated neurodegeneration, Lesch-Nyhan syndrome, and postanoxic and tardive dystonia. The pathophysiology of intermittent severe tongue protrusion remains unknown. Tongue protrusion dystonia is often unresponsive to oral drugs but may benefit from botulinum toxin injections into the genioglossus muscle. Bilateral deep brain pallidal stimulation was beneficial in two cases.

Adolescent↗

PubMed2006

Measuring quality of life in PSP: the PSP-QoL.

OBJECTIVE: To develop a new patient-reported outcome measure for progressive supranuclear palsy (PSP) and to test its psychometric properties. METHODS: First, the authors generated a pool of potential scale items from in-depth patient interviews. Second, the authors administered these items, in the form of a questionnaire, to a sample of people with PSP and traditional psychometric methods were used to develop a rating scale satisfying standard criteria for reliability and validity. Third, the authors examined the psychometric properties of the rating scale in a second sample. RESULTS: In stage 1, a pool of 87 items was generated from 27 patient interviews. In stage 2, a scale with two subscales (physical, 22 items; mental, 23 items), satisfying standard criteria for reliability and validity, was developed from the response data of 225 patients with PSP. In stage 3, the scale was examined in 188 people with PSP. Missing data were low, scores in both subscales were evenly distributed, floor and ceiling effects were small. Reliability was high (Cronbach's alpha 0.93, 0.95; test-retest 0.95, 0.92). Validity was supported by the interscale intercorrelation (0.60), factor analysis, and the magnitude and pattern of correlations with four other rating scales, disease severity, and disease duration. The psychometric properties of the new scale were similar in the United Kingdom and North America, and in clinic- and community-based samples studied. CONCLUSIONS: The Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL) may be a helpful patient-reported scale for clinical trials and studies in PSP.

Aged↗

PubMed2006

The alpha-synuclein gene in multiple system atrophy.

BACKGROUND: The formation of alpha-synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested. METHOD: The linkage disequilibrium (LD) structure of the alpha-synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated. RESULTS AND CONCLUSION: In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag-defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases.

Gene Expression↗

PubMed2005

The European Multiple System Atrophy-Study Group (EMSA-SG).

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.

Animals↗

PubMed2005

The epsilon-sarcoglycan gene in myoclonic syndromes.

Mutations in the epsilon-sarcoglycan gene (SGCE) are associated with familial myoclonus dystonia, but the full spectrum of the phenotype may not be fully defined. We screened 58 individuals with a range of myoclonic/dystonic syndromes for SGCE mutations. We found mutations (three of them novel) in six (21%) of the 29 patients with essential myoclonus and myoclonic dystonia, but did not find mutations in the 29 patients with other phenotypes.

Age of Onset↗

PubMed2005

Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation.

Parkin disease is usually autosomal recessive; however, two studies have shown that asymptomatic heterozygotes have nigrostriatal dysfunction and even manifest subtle extrapyramidal signs. The authors used 18F-dopa PET to study 13 asymptomatic parkin heterozygotes and found a significant reduction of (18)F-dopa uptake in caudate, putamen, ventral, and dorsal midbrain compared with control subjects. Four had subtle extrapyramidal signs. Parkin heterozygosity is a risk factor for nigrostriatal dysfunction and in some may contribute to late-onset Parkinson disease.

Aged↗

PubMed2005

Measuring health-related quality of life in patients with progressive supranuclear palsy.

The development of psychometrically sound health-related quality of life (Hr-QoL) instruments has made it possible to assess subjectively experienced Hr-QoL quantitatively, and to incorporate Hr-QoL as a measure in medical research and clinical trials. Hr-QoL in patients with progressive supranuclear palsy (PSP) has been measured using generic (not disease-specific) instruments, or Parkinson's disease-specific scales. We give an overview of the development of a disease-specific Hr-QoL instrument for patients with PSP. Based on interviews with 27 patients with PSP a preliminary Hr-QoL instrument was developed and administered to over 300 people with PSP in the UK and US. Following psychometric analysis a rating scale with a physical and a mental subscale emerged. In this patient sample, both subscales satisfied criteria for scaling assumptions, acceptability, reliability and validity (correlations with other measures consistent with a priori hypotheses). The psychometric properties of this questionnaire are undergoing further evaluation.

Aged↗

PubMed2005

Parkinsonism following bilateral lesions of the globus pallidus: performance on a variety of motor tasks shows similarities with Parkinson's disease.

OBJECTIVES: The authors report the results of detailed investigations into the motor function of a patient who, after a heavy drinking binge and subsequent unconsciousness, respiratory acidosis, and initial recovery, developed parkinsonism characterised by hypophonic speech and palilalia, "fast micrographia", impaired postural reflexes, and brady/akinesia in proximal (but not distal) alternating upper limb movements. METHODS: In addition to brain magnetic resonance imaging (MRI), different aspects of motor function were investigated using reaction time (RT) tasks, pegboard and finger tapping tasks, flex and squeeze tasks, movement related cortical potentials (MRCPs), and contingent negative variation (CNV). Cognitive function was also assessed. The results were compared to those previously reported in patients with Parkinson's disease (PD). RESULTS: Brain MRI showed isolated and bilateral globus pallidus (GP) lesions covering mainly the external parts (GPe). These lesions were most probably secondary to respiratory acidosis, as other investigations failed to reveal an alternative cause. The results of the RT tasks showed that the patient had difficulties in preparing and maintaining preparation for a forthcoming movement. MRCP and CNV studies were in line with this, as the early component of the MRCP and CNV were absent prior to movement. The patient's performance on pegboard and finger tapping, and flex and squeeze tasks was normal when performed with one hand, but clearly deteriorated when using both hands simultaneously or sequentially. CONCLUSIONS: In general, the present results were similar to those reported previously in patients with PD. This provides further indirect evidence that the output of globus pallidus is of major importance in abnormal motor function in PD. The possible similarities of the functional status of GP in PD and our case are discussed.

Acidosis, Respiratory↗

PubMed2004

Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease.

The authors studied whether olfactory dysfunction is present in parkin disease using the University of Pennsylvania Smell Identification Test (UPSIT). The mean UPSIT score in parkin patients was 27.3 (95% CI 24.4 to 30.2). This did not differ from the normal group mean of 29.4 (95% CI 28.0 to 30.7; p = 0.22) but was higher than the Parkinson disease group (mean 14.3; 95% CI 12.2 to 19.5; p < 0.0001) and the parkin-negative group (mean 17.1; 95% CI 14.8 to 16.3; p < 0.0001) values. Parkin disease may be a distinct and separate entity from Parkinson disease.

Age of Onset↗

PubMed2004

Tau gene and Parkinson's disease: a case-control study and meta-analysis.

OBJECTIVE: To investigate whether the tau H1 haplotype is a genetic risk factor in Parkinson's disease and to report a meta-analysis on all previously published data METHODS: and results: In a sample of 580 patients with Parkinson's disease and 513 controls there was an increased risk of Parkinson's disease for both the tau H1 haplotype (p<or=0.0064; odds ratio (OR) 1.34 (95% confidence interval (CI), 1.04 to 1.72)) and the H1H1 genotype (p<or=0.0047; OR 1.42 (1.1 to 1.83)). Under a fixed effect model, the summary OR for this showed that individuals homozygous for the H1 allele were 1.57 times more likely to develop Parkinson's disease than individuals carrying the H2 allele (95% CI 1.33 to 1.85; p<0.00001). The population attributable risk for the tau variant, for the main comparison of H1H1 against H2 carriers, was 24.8% for all studies combined. CONCLUSIONS: Homozygosity for the tau H1 is associated with an increased risk of Parkinson's disease. This adds to the growing body of evidence that common genetic variation contributes to the pathogenesis of this disorder.

Alleles↗

PubMed2004

DJ-1 mutations in Parkinson's disease.

Mutations in the DJ-1 gene have recently been shown to cause autosomal recessive Parkinson's disease. To estimate the prevalence of this mutation, an analysis was undertaken of 39 index cases of Parkinson's disease in whom a family history suggested autosomal recessive inheritance. No DJ-1 mutations were found in these patients, indicating that this gene is unlikely to be of numerical significance in clinical practice. The hypothesis was also tested that young onset Parkinson's disease patients in whom, despite extensive analysis, only a single heterozygous parkin mutation was found, might harbour a second mutation in the DJ-1 gene--that is, digenic inheritance. No patient was found with a single mutation in both DJ-1 and parkin genes, making this mode of inheritance unlikely. Finally it was confirmed that PARK6 and PARK7 (DJ-1), despite being phenotypically similar and mapping to the same small chromosomal region of 1p36, are caused by mutations in separate genes.

Age of Onset↗

PubMed2003

[11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy.

Microglia, the brain's intrinsic macrophages, bind (R)-PK11195 when activated by neuronal injury. The authors used [11C](R)-PK11195 PET to localize in vivo microglial activation in patients with multiple system atrophy (MSA). Increased [11C](R)-PK11195 binding was primarily found in the dorsolateral prefrontal cortex, putamen, pallidum, pons, and substantia nigra, reflecting the known distribution of neuropathologic changes in MSA. Providing an indicator of disease activity, [11C](R)-PK11195 PET can thus be used to characterize the in vivo neuropathology of MSA.

Aged↗

PubMed2003

Tau exon 10 +16 mutation FTDP-17 presenting clinically as sporadic young onset PSP.

The authors describe a case of clinically diagnosed young onset progressive supranuclear palsy (PSP) with symptom onset at 40 years of age and no family history of neurodegenerative disease. There was no history of falls during the first year of symptoms. Genetic analysis identified this patient as having a tau exon 10 +16 mutation (MAPT, IVS10, C-U, +16). Neuropathologic examination confirmed the genetic diagnosis of frontotemporal dementia. An age at onset younger than 50 years combined with the absence of early falls may indicate the possibility of a tau mutation in clinically diagnosed PSP.

Adult↗

PubMed2003

Quality of life in patients with orthostatic tremor.

We assessed health-related quality of life (QoL) and depression, using the SF-36 and the Beck Depression Inventory (BDI), in 20 orthostatic tremor (OT) patients. All dimensions of the SF-36 were markedly reduced in OT and depression was found in 11 patients. The BDI score correlated significantly with several SF-36 subscores. We conclude that OT strongly impacts on QoL. The results highlight the importance of recognizing and treating depression in patients with OT.

Aged↗

PubMed2002

Do published criteria improve clinical diagnostic accuracy in multiple system atrophy?

OBJECTIVE: To assess the accuracy of a clinical diagnosis of multiple system atrophy (MSA) and compare it to the Quinn and Consensus criteria for MSA using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. METHODS: Fifty-nine cases with a neurologic diagnosis of MSA when last assessed prior to death were studied. RESULTS: In 51 (86%) of these cases, the diagnosis of MSA was confirmed pathologically. False positive diagnoses included PD (n = 6), progressive supranuclear palsy (n = 1), and cerebrovascular disease (n = 1). When applying either set of diagnostic criteria, a diagnosis of probable MSA gave lower sensitivity but higher positive predictive value than one of possible MSA. Application of either set of diagnostic criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by the last clinic visit. CONCLUSIONS: This study shows a high diagnostic accuracy for the clinical diagnosis of MSA by neurologists, with PD accounting for most of the false positive diagnoses. Application of either Quinn or Consensus criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by last clinic visit.

Adult↗

PubMed2002

Sequence analysis of tau in familial and sporadic progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a tau deposition neurodegenerative disorder which usually occurs in sporadic form and is associated with a common variant of the tau gene. Rare familial forms of PSP have been described. Recently familial frontotemporal dementia linked to chromosome 17 (FTDP-17) has been shown to be due to mutations in tau and there may be a clinical and pathological overlap between PSP and FTDP-17. In this study we have analysed the tau sequence in two small families with PSP, and a number of clinically typical and atypical sporadic cases with pathological confirmation of the diagnosis. The tau mutations described in FTDP-17 were not found in the most clinically diagnosed patients with PSP. This suggests that usually FTDP-17 and PSP, including the rare familial form of PSP, are likely to be separate conditions and that usually PSP and typical PSP-like syndromes are not due to mutations in tau.

Aged↗

PubMed2002

How valid is the clinical diagnosis of Parkinson's disease in the community?

BACKGROUND: Many patients diagnosed with Parkinson's disease are later found to have an erroneous diagnosis, often only when they come to necropsy; conversely, many patients with Parkinson's disease in the community remain undiagnosed. OBJECTIVE: To assess the validity of a clinical diagnosis of parkinsonism in the general population according to strict published criteria. METHODS: As part of a population based study on the prevalence of Parkinson's disease in London, all patients were identified with a diagnosis of parkinsonism, tremor with onset over age 50 years, or who had ever received antiparkinsonian drugs. All patients who agreed to participate were diagnosed according to strict clinical diagnostic criteria, after a detailed neurological interview and examination and discussion of the findings with examination of their video recordings. Follow up information was obtained over a period of at least one year, and atypical cases were reviewed at the end of the study. RESULTS: A diagnosis of probable Parkinson's disease was confirmed in 83% of patients with this diagnosis, including three (2%) in whom atypical features were found that were insufficient to discard a diagnosis of Parkinson's disease. Two additional patients (2%) were found to have possible Parkinson's disease. However, in 15% of patients the diagnosis was unequivocally rejected. Conversely, 13 patients who had previously not been diagnosed with Parkinson's disease (19%) were found to have this disorder. CONCLUSIONS: At least 15% of patients with a diagnosis of Parkinson's disease in the population do not fulfil strict clinical criteria for the disease, and approximately 20% of patients with Parkinson's disease who have already come to medical attention have not been diagnosed as such.

Aged↗