26 results on '"McCusker EA"'
Search Results
2. A Phenotypic Atlas for Huntington Disease Based on Data From the Enroll-HD Cohort Study.
- Author
-
Langbehn DR, Sathe SS, Loy C, Sampaio C, and Mccusker EA
- Abstract
Background and Objectives: The variable CAG repeat expansion in the huntingtin gene and its inverse relationship to motor dysfunction onset are fundamental features of Huntington disease (HD). However, the wider phenotype (including non-motor features) at particular CAG lengths, ages, and functional levels is less well-characterized. The large number of participants in the Enroll-HD observational study enables the development of a phenotype atlas that summarizes the range and distribution of HD phenotypes, including outliers and possible clusters, with respect to various CAG repeat lengths, age ranges, and declining functional levels., Methods: Enroll-HD is an ongoing prospective longitudinal observational study that collects natural history data, releasing periodic data sets, in people with HD (PwHD) and controls. Core assessments at annual visits focus on behavioral, cognitive, motor, and functional status. Periodic data set 5, used for the development of the first iteration of the Enroll-HD Phenotype Atlas (EHDPA), included all eligible data collected through October 31, 2020. The atlas is based on subsets (cells) of descriptive data for all motor, cognitive, psychiatric, and functional measures that are routinely collected at most Enroll-HD sites, analyzed by single CAG lengths and 5-year age blocks., Results: Data from 42,840 visits from 15,982 unique PwHD were available for analysis. At baseline, participants had a mean ± SD age of 48.9 ± 13.9 years and CAG repeat length of 43.4 ± 3.6 and 54.1% were female. The EHDPA includes 223 age-by-CAG subsets for CAG repeats between 36 and 69 with five-year age brackets starting from 20-24 years up to 85-89 years. The atlas can be browsed at enroll-hd.org/for-researchers/atlas-of-hd-phenotype/., Discussion: The EHDPA summarizes the spectrum and distribution of HD phenotypes, including outliers and possible clusters, in all domains of disease involvement for the range of CAG repeat lengths, ages, and functional levels. Its availability in an easy-to-use online format will assist clinicians in tracking disease progression in PwHD by identifying phenotypic features most associated with loss of function and enabling conversations related to prognosis. The observable patterns in the EHDPA should also catalyze more formal multidomain characterization of motor, cognitive, and psychiatric progression and their relationships to functional decline and disease modifiers., Trial Registration Information: Enroll-HD is registered with clinicaltrials.gov: NCT01574053., Competing Interests: D.R. Langbehn reports personal consulting fees and nonfinancial support from Voyager Therapeutics, personal consulting fees from Novartis, personal consulting fees from uniQure, personal consulting fees from Takeda, personal consulting fees from AskBio, and personal consulting fees from Guidepoint Consultants, all outside the submitted work; Clement Loy is supported by the Australian National Medical and Health Research Council; Elizabeth McCusker has nothing to report; Swati Sathe and Cristina Sampaio are employed by CHDI Management as advisors to CHDI Foundation. Go to Neurology.org/NG for full disclosures., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2023
- Full Text
- View/download PDF
3. Scientific, Ethical, and Practical Considerations for the Testing and Disclosure of Alzheimer Disease Biomarkers.
- Author
-
McCusker EA and Loy CT
- Subjects
- Humans, Biomarkers, Disclosure, Alzheimer Disease diagnosis
- Published
- 2023
- Full Text
- View/download PDF
4. Prevalent Nonmotor Symptoms Associated With Huntington Disease: Challenging to Interpret and With Early Impact on Function.
- Author
-
McCusker EA and Loy CT
- Subjects
- Cognition, Humans, Autonomic Nervous System Diseases, Huntington Disease complications, Parkinson Disease
- Published
- 2021
- Full Text
- View/download PDF
5. End of life: Expert care and support, not physician-hastened death.
- Author
-
Masdeu JC, Aksamit AJ, Carver AC, Foley KM, Kass JS, Martin RA, McCusker EA, McQuillen MP, Mehanna R, Payne R, Victor SJ, and Warach S
- Subjects
- Humans, Netherlands, Neurology ethics, Neurology methods, Societies, Medical, United States, Palliative Care ethics, Palliative Care methods, Terminal Care ethics, Terminal Care methods
- Abstract
In legal physician-hastened death, a physician prescribes medication with the primary intent of causing the death of a willing terminally ill patient. This practice differs radically from palliative sedation, intended to relieve a patient's suffering rather than cause a patient's death. In this position paper, we argue that the practice of physician-hastened death is contrary to the interests of patients, their families, and the sound ethical practice of medicine. Therefore, the American Academy of Neurology should advise its members against this practice, as it had done until 2018., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2019
- Full Text
- View/download PDF
6. Movement Disorder Society Task Force Viewpoint: Huntington's Disease Diagnostic Categories.
- Author
-
Ross CA, Reilmann R, Cardoso F, McCusker EA, Testa CM, Stout JC, Leavitt BR, Pei Z, Landwehrmeyer B, Martinez A, Levey J, Srajer T, Bang J, and Tabrizi SJ
- Abstract
Competing Interests: No relevant funding sources or conflicts of interest, given the nature of the article. No off‐label uses of medications or other treatments discussed. Participants received financial support for travel to the meeting February 4 and 5, 2017, from the Movement Disorder Society. Costs for phone conferences were paid by the Movement Disorder Society.
- Published
- 2019
- Full Text
- View/download PDF
7. Huntington Disease: The Complexities of Making and Disclosing a Clinical Diagnosis After Premanifest Genetic Testing.
- Author
-
McCusker EA and Loy CT
- Subjects
- Humans, Physician-Patient Relations, Disclosure ethics, Huntington Disease diagnosis, Huntington Disease genetics, Truth Disclosure ethics
- Abstract
The management of patients and families affected by Huntington disease (HD) is complicated by several factors, both practical and ethical. It can be difficult to determine the onset of clinically manifest HD (mHD). In addition, it can be challenging to decide when to disclose the diagnosis to the affected individual. Firstly, the features of HD, an incurable, inherited, neurocognitive disorder that often manifests in young adulthood, influence how the person presents and accepts a diagnosis. Secondly, a positive genetic test for HD may result in a genetic diagnosis, sometimes years before the development of clinical features and the diagnosis of mHD. Thirdly, observational studies of unaffected gene expansion carriers documented HD manifestations up to 10 years before the typical presentation for diagnosis. These developments may permit earlier genetic diagnosis and information regarding the patient's likely status with respect to the development of clinical disease. Making the genetic diagnosis of HD and providing information regarding disease status, earlier rather than later, respects the person's right to know and preserves honesty in the doctor/patient relationship. Conversely, delaying the diagnosis respects the right not to know, avoids potential discrimination, and permits the person to live a "normal" life for longer, in the context of a disease without cure. This discussion has implications for other inherited and neurocognitive disorders., Competing Interests: Funding: None. Conflict of Interests: The authors report no conflict of interest. Ethics Statement: Not applicable for this category of article.
- Published
- 2017
- Full Text
- View/download PDF
8. What do we know about Late Onset Huntington's Disease?
- Author
-
Chaganti SS, McCusker EA, and Loy CT
- Subjects
- Age of Onset, Humans, Huntington Disease genetics, Huntington Disease physiopathology, Huntington Disease epidemiology
- Abstract
Background: Although the typical age of onset for Huntington's disease (HD) is in the fourth decade, between 4.4-11.5% of individuals with HD have a late onset (over 60 years of age). Diagnosis of Late onset HD (LoHD) can be missed, due to the perceived low likelihood of HD in the over 60-year-olds., Objective: To review the epidemiology, genotype and phenotype of LoHD., Methods: We systematically searched MEDLINE, EMBASE and Web of Science (inception-November 2016). Web of Science was then used to search for papers citing identified studies. Content experts were consulted for any additional studies. We included all studies reporting the clinical phenotype of LoHD for more than one participant., Results: 20 studies were identified from a potential list of 1243. Among Caucasian HD cohorts, 4.4-11.5% of individuals have LoHD, and this proportion may be increasing. Proportion of LoHD without a positive family history ranges from 3-68%. 94.4% of reported cases of LoHD had CAG repeat lengths of ≤44. Motor manifestations are the commonest initial presentation, although 29.2% presented with non-motor manifestations as the first clinical feature in one case series. Individuals with LoHD may have slower progression of illness. Cognitive impairment rather than chorea may be the major source of disability in this group., Conclusions: LoHD represents a substantial proportion of new diagnoses of HD and has some unique features. Further characterization of this population will aid clinicians in diagnosis.
- Published
- 2017
- Full Text
- View/download PDF
9. Medical management of motor manifestations of Huntington disease.
- Author
-
McCusker EA and Loy CT
- Subjects
- Antipsychotic Agents adverse effects, Chorea drug therapy, Deglutition Disorders chemically induced, Deglutition Disorders drug therapy, Dyskinesia, Drug-Induced drug therapy, Dystonia drug therapy, Humans, Huntington Disease drug therapy, Huntington Disease complications, Movement Disorders drug therapy
- Abstract
The motor and movement disorders of Huntington disease (HD) are managed in the context of the other disease features. Chorea and dystonia are the most common HD-associated movement disorders, and they can be assessed on research rating scales. However other motor manifestations have a significant impact. In particular, dysphagia influences choice and tolerance of treatment for the movement disorder, as will comorbidities, patient awareness, and distress related to the motor feature or movement. Treatment for other disease features may aggravate the motor disorder, e.g., increased swallowing difficulty associated with antipsychotic agents. Basic principles in deciding to institute a treatment are outlined as well as treatment of specific motor manifestations and movements. There is a paucity of evidence to support the treatments available for the motor disorder, with only one agent with class 1 evidence, tetrabenazine, for chorea. There are, however, treatments informed by expert opinion which reflect the management of a wider HD phenotype than that represented in clinical trials. Some treatments are based on evidence from use in other conditions. Medical management is usually undertaken later in the disease with concurrent nonmedical interventions after multidisciplinary assessments. Medication review with HD progression is essential., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
10. Motor onset and diagnosis in Huntington disease using the diagnostic confidence level.
- Author
-
Liu D, Long JD, Zhang Y, Raymond LA, Marder K, Rosser A, McCusker EA, Mills JA, and Paulsen JS
- Subjects
- Adult, Age Factors, Age of Onset, Female, Humans, Longitudinal Studies, Male, Middle Aged, Prodromal Symptoms, Risk, Disease Progression, Huntington Disease diagnosis, Huntington Disease genetics, Trinucleotide Repeats
- Abstract
Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale. HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, was associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11% (95% CI 7-15%) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47% (95% CI 27-69%). Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models.
- Published
- 2015
- Full Text
- View/download PDF
11. Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study.
- Author
-
Paulsen JS, Long JD, Johnson HJ, Aylward EH, Ross CA, Williams JK, Nance MA, Erwin CJ, Westervelt HJ, Harrington DL, Bockholt HJ, Zhang Y, McCusker EA, Chiu EM, and Panegyres PK
- Abstract
There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington's disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7-12 years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.
- Published
- 2014
- Full Text
- View/download PDF
12. Feasibility of Huntington disease trials in the disease prodrome.
- Author
-
McCusker EA and Myers RH
- Subjects
- Humans, Brain drug effects, Cognition Disorders prevention & control, Creatine pharmacology, Huntington Disease prevention & control
- Published
- 2014
- Full Text
- View/download PDF
13. Unawareness of motor phenoconversion in Huntington disease.
- Author
-
McCusker EA, Gunn DG, Epping EA, Loy CT, Radford K, Griffith J, Mills JA, Long JD, and Paulsen JS
- Subjects
- Adult, Analysis of Variance, Chi-Square Distribution, Cognition Disorders diagnosis, Disease Progression, Female, Humans, Huntington Disease genetics, Huntington Disease pathology, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Phenotype, Psychomotor Performance, Self Report, Severity of Illness Index, Statistics as Topic, Awareness, Cognition Disorders etiology, Huntington Disease complications, Huntington Disease psychology
- Abstract
Objective: To determine whether Huntington disease (HD) mutation carriers have motor symptoms (complaints) when definite motor onset (motor phenoconversion) is diagnosed and document differences between the groups with and without unawareness of motor signs., Methods: We analyzed data from 550 HD mutation carriers participating in the multicenter PREDICT-HD Study followed through the HD prodrome. Data analysis included demographics, the Unified Huntington's Disease Rating Scale (UHDRS) and the Participant HD History of symptoms, self-report of progression, and cognitive, behavioral, and imaging measures. Unawareness was identified when no motor symptoms were self-reported but when definite motor HD was diagnosed., Results: Of 38 (6.91%) with onset of motor HD, almost half (18/38 = 47.36%) had no motor symptoms despite signs of disease on the UHDRS motor rating and consistent with unawareness. A group with motor symptoms and signs was similar on a range of measures to the unaware group. Those with unawareness of HD signs reported less depression. Patients with symptoms had more striatal atrophy on imaging measures., Conclusions: Only half of the patients with newly diagnosed motor HD had motor symptoms. Unaware patients were less likely to be depressed. Self-report of symptoms may be inaccurate in HD at the earliest stage.
- Published
- 2013
- Full Text
- View/download PDF
14. Is a motor criterion essential for the diagnosis of clinical huntington disease?
- Author
-
Loy CT and McCusker EA
- Abstract
While there has been a guideline for laboratory/genetic diagnosis of Huntington Disease (HD) since 1998, no such statement exists for the diagnosis of clinical HD. Informally, the most frequently used criteria for diagnosis of clinical HD is 'Motor 4' within the Unified Huntington Disease Rating Scale '99 (motor), made when the rater is highly confident that 'motor abnormalities observed are unequivocal signs of HD'. Recent studies involving pre-manifest individuals illustrated the shortcomings of this motor-only diagnostic approach. For instance, PREDICT-HD found cognitive changes decades before the expected date of motor diagnosis. Using a number of case studies, we highlight some of the subtleties involved in diagnosing clinical HD, in the absence of unequivocal motor signs for HD. New, broader, criteria for the diagnosis of clinical HD would be helpful in many ways. However its formulation will need to flexible rather than prescriptive, and will require extensive consultation with clinicians and families with HD.
- Published
- 2013
- Full Text
- View/download PDF
15. Doctors breaching patient privacy: Orwell redux.
- Author
-
Suthers GK, McCusker EA, and Wake SA
- Subjects
- Genetic Privacy legislation & jurisprudence, Humans, New South Wales, Physicians ethics, Confidentiality legislation & jurisprudence, Physicians legislation & jurisprudence
- Published
- 2011
- Full Text
- View/download PDF
16. Alerting genetic relatives to a risk of serious inherited disease without a patient's consent.
- Author
-
Suthers GK, McCusker EA, and Wake SA
- Subjects
- Australia, Genetic Diseases, Inborn therapy, Guidelines as Topic, Humans, Confidentiality legislation & jurisprudence, Genetic Diseases, Inborn diagnosis, Genetic Diseases, Inborn genetics, Informed Consent legislation & jurisprudence, Truth Disclosure
- Published
- 2011
- Full Text
- View/download PDF
17. Disgust and happiness recognition correlate with anteroventral insula and amygdala volume respectively in preclinical Huntington's disease.
- Author
-
Kipps CM, Duggins AJ, McCusker EA, and Calder AJ
- Subjects
- Adult, Amygdala physiopathology, Brain Mapping, Cerebral Cortex physiopathology, Facial Expression, Female, Humans, Huntington Disease genetics, Huntington Disease physiopathology, Huntington Disease psychology, Male, Middle Aged, Neuropsychological Tests, Psychomotor Performance physiology, Severity of Illness Index, Statistics as Topic, Amygdala pathology, Cerebral Cortex pathology, Emotions physiology, Huntington Disease pathology, Pattern Recognition, Visual physiology, Recognition, Psychology physiology
- Abstract
Patients with Huntington's disease (HD) can show disproportionate impairments in recognizing facial signals of disgust, but the neural basis of this deficit remains unclear. Functional imaging studies have implicated the anterior insula in the ability to recognize disgust, but have identified other structures as well, including the basal ganglia. In view of variable insula and basal ganglia volume changes in HD, we used voxel-based morphometry to map regional variations in gray matter (GM) volume in participants carrying the mutation for HD, and correlated this with their performance on a test of facial emotion recognition for six basic emotions (disgust, fear, anger, happiness, sadness, surprise). The volume of the anteroventral insula was strongly correlated with performance on the disgust recognition task. The amygdala volume (bilaterally) correlated with the ability to recognize happy facial expressions. There was marked specificity of the regional correlations for the emotion involved. Recognition of other emotion expressions, or more general cognitive or motor performance as measured by a standardized rating scale, did not correlate with regional brain volume in this group. Control participants showed no effect for any measure. The strong linear correlations for disgust and happiness recognition imply direct involvement of the anterior insula in disgust appreciation, and a similar role for the amygdala in recognizing happy facial expressions. The absence of a significant correlation with the basal ganglia suggests a less critical role for these structures in disgust recognition than has previously been suggested. The findings also highlight the role of neurodegenerative diseases combined with statistical imaging techniques in elucidating the brain basis of behavior and cognition.
- Published
- 2007
- Full Text
- View/download PDF
18. Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study.
- Author
-
Kipps CM, Duggins AJ, Mahant N, Gomes L, Ashburner J, and McCusker EA
- Subjects
- Adult, Atrophy pathology, Caudate Nucleus pathology, Disease Progression, Female, Follow-Up Studies, Globus Pallidus pathology, Humans, Huntington Disease epidemiology, Huntington Disease genetics, Incidence, Magnetic Resonance Imaging, Male, Mesencephalon pathology, Point Mutation genetics, Putamen pathology, Substantia Nigra pathology, Trinucleotide Repeats genetics, Brain pathology, Huntington Disease pathology
- Abstract
Background and Objectives: Regional cerebral atrophy occurs in carriers of the Huntington's disease (HD) gene mutation before clinical diagnosis is possible. The current inability to reliably measure progression of pathology in this preclinical phase impedes development of therapies to delay clinical onset. We hypothesised that longitudinal statistical imaging would detect progression of structural pathology in preclinical carriers of the HD gene mutation, in the absence of measurable clinical change., Methods: Thirty subjects (17 preclinical mutation positive, 13 mutation negative) underwent serial clinical and magnetic resonance imaging (MRI) assessments over an interval of 2 years. Statistically significant changes in regional grey and white matter volume on MRI were analysed using tensor based morphometry (TBM). This technique derives a voxel-wise estimation of regional tissue volume change from the deformation field required to warp a subject's early to late T1 images., Results: Over 2 years, there was progressive regional grey matter atrophy in mutation-positive relative to negative subjects, without significant clinical progression of disease. Significant grey matter volume loss was limited to bilateral putamen and globus pallidus externa (GPe), left caudate nucleus, and left ventral midbrain in the region of the substantia nigra., Conclusions: While these results are consistent with previous cross sectional pathologic and morphometric studies, significant progression of atrophy in HD before the onset of significant clinical decline is now demonstrable with longitudinal statistical imaging. Such measures could be used to assess the efficacy of potential disease modifying drugs in slowing the progression of pathology before confirmed clinical onset of HD.
- Published
- 2005
- Full Text
- View/download PDF
19. The specialist neurologist and the "new genetics".
- Author
-
McCusker EA
- Subjects
- Adult, Genetic Counseling, Humans, Models, Genetic, Trinucleotide Repeats, DNA genetics, Huntington Disease genetics, Neurology
- Abstract
The "new genetics" will require specialist physicians to deal with an increasing number of genetic issues. Huntington disease (HD) is a rare single gene adult-onset fatal neurodegenerative disorder. It provides a model to illustrate the role of the specialist physician in the new genetics. DNA testing options in HD include diagnostic DNA tests to confirm a provisional diagnosis, and predictive or presymptomatic DNA tests to determine whether disease will develop in an at-risk individual. The specialist physician is well positioned to interact with the genetics services by providing in-depth knowledge of the clinical implications. This will become particularly relevant as the more complex multifactorial disorders (eg, Alzheimer disease) are understood at the DNA level. For optimal use of the new genetics, a team approach is essential to ensure that all areas of expertise are covered.
- Published
- 2003
- Full Text
- View/download PDF
20. Postmortem analysis of bilateral subthalamic electrode implants in Parkinson's disease.
- Author
-
Henderson JM, Pell M, O'Sullivan DJ, McCusker EA, Fung VS, Hedges P, and Halliday GM
- Subjects
- Brain pathology, Brain surgery, Electrodes, Implanted, Fatal Outcome, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Parkinson Disease pathology, Subthalamic Nucleus pathology, Electric Stimulation Therapy methods, Parkinson Disease surgery, Subthalamic Nucleus surgery
- Abstract
This is the second neuropathological report detailing bilateral electrodes targeting the subthalamic nucleus (STN) in idiopathic Parkinson's disease (PD). The patient presented with unilateral tremor-dominant parkinsonism. Bilateral STN stimulation was carried out 7 years later due to significant disease progression and severe motor fluctuations. The patient exhibited bilateral improvements in rigidity and bradykinesia both intraoperatively and postoperatively. The patient died 2 months later from aspiration pneumonia. Neuropathological examination confirmed both the diagnosis of PD and the electrode placements. The tip of the left electrode was located medially and posteriorly in the left STN and the tip of the right electrode entered the base of the thalamus/zona incerta immediately above the right STN. Tissue changes associated with the subthalamic electrode tracts included mild cell loss, astrogliosis, and some tissue vacuolation. Our postmortem analysis indicates little tissue damage associated with STN stimulation for PD., (Copyright 2001 Movement Disorder Society.)
- Published
- 2002
- Full Text
- View/download PDF
21. Prevalence of Huntington disease in New South Wales in 1996.
- Author
-
McCusker EA, Casse RF, Graham SJ, Williams DB, and Lazarus R
- Subjects
- Adult, Aged, Aged, 80 and over, DNA analysis, Epidemiologic Methods, Female, Humans, Male, Middle Aged, New South Wales epidemiology, Prevalence, Huntington Disease epidemiology
- Abstract
Objective: To estimate the prevalence of Huntington disease (HD) in New South Wales on Australian Census Day (6 August) 1996., Design: Survey of records of the Huntington Disease Service and major hospitals, and of neurologists, psychiatrists, clinical geneticists and genetic counsellors., Subjects and Setting: All patients in NSW who, on Census Day 1996, either had a definite diagnosis of HD (motor signs of chorea or ataxia and family history of HD or positive DNA test result) or would have had signs and later received a definite diagnosis (assessed 1 April 1997 to 1 July 1999)., Main Outcome Measures: Prevalence (HD patients per 100,000 population); patient characteristics; year and basis of diagnosis., Results: 380 patients with definite HD were identified, giving a prevalence of HD in NSW in 1996 of 6.29 per 100,000 population (95% CI, 5.68-6.96). A third of HD patients were aged 60 years or older. Diagnosis was confirmed by DNA testing for 171 patients (45%), including 30 (8%) with no recorded family history. Average numbers of new diagnoses per year were 11.8 (1984-1988), 21.8 (1989-1993) and 28.6 (1994-1998). Estimated number of people with a 50% risk of inheriting the HD mutation was 25.2 per 100,000 population. Estimated incidence of HD in 1996 was 0.65 per 100,000 population., Conclusions: Prevalence of HD in NSW is similar to estimated prevalence in other Australian and Western populations. Increasing numbers of cases are being diagnosed, and the 18 chronic care beds currently designated for HD patients in NSW are unlikely to be sufficient.
- Published
- 2000
- Full Text
- View/download PDF
22. Significant loss of pyramidal neurons in the angular gyrus of patients with Huntington's disease.
- Author
-
Macdonald V, Halliday GM, Trent RJ, and McCusker EA
- Subjects
- Aged, Atrophy pathology, Female, Glial Fibrillary Acidic Protein analysis, Humans, Immunohistochemistry, Male, Middle Aged, Parietal Lobe chemistry, Pyramidal Cells chemistry, Huntington Disease pathology, Parietal Lobe pathology, Pyramidal Cells pathology
- Abstract
The primary site of pathology in Huntington's disease (HD) is the caudate nucleus. However, cortical changes are also commonly reported. While many researchers have studied pathology in the frontal lobe, little attention has been paid to posterior cortical regions. The aim of this study is to examine pathology in the parietal lobe in patients with HD as it has specific projections to the caudate nucleus. Post-mortem brain tissue was obtained from HD patients with both a positive family history and clinicopathological diagnosis (n = 6; Vonsattel grades 2-4) as well as from neurologically normal controls (n = 6). The angular gyrus of the parietal lobe was sampled and cellular quantification of SMI-32 immunohistochemically detected pyramidal neurons performed. Cortical blocks were sectioned at 50 microns on a cryostat and stained immunohistochemically using antigen retrieval methods and peroxidase visualization. HD subjects had noticeable histological changes including smaller neurons and a disruption of cortical laminar pattern. Quantification using a point counting method to find the areal fraction of immunoreactive neurons revealed a severe loss of pyramidal neurons in the angular gyrus of HD subjects compared with controls (reduced on average to 55% of mean control values, P = 0.038 using the Mann-Whitney U-test). This striking cortical pathology suggests that HD may preferentially target posterior cortical regions, particularly the angular gyrus which has a significant projection to the caudate nucleus in primates.
- Published
- 1997
- Full Text
- View/download PDF
23. Huntington's disease: a challenge for out times.
- Author
-
Turner DR and McCusker EA
- Subjects
- Ethics, Medical, Humans, Huntington Disease prevention & control, Practice Guidelines as Topic, Genetic Testing, Huntington Disease diagnosis, Huntington Disease genetics, Molecular Biology
- Published
- 1997
24. Recovery from the 'locked-in' syndrome.
- Author
-
McCusker EA, Rudick RA, Honch GW, and Griggs RC
- Subjects
- Adult, Aged, Cerebral Hemorrhage complications, Cerebral Hemorrhage diagnosis, Cerebral Infarction complications, Cerebral Infarction diagnosis, Female, Humans, Male, Middle Aged, Pons blood supply, Prognosis, Quadriplegia diagnosis, Tomography, X-Ray Computed, Vertebrobasilar Insufficiency complications, Vertebrobasilar Insufficiency diagnosis, Quadriplegia rehabilitation
- Abstract
Four patients made substantial recovery following the locked-in syndrome of vascular origin. Clinical and radiologic features supported the presence of ventral pontine infarction secondary to basilar artery occlusion. Quadriplegia and mutism persisted for one to 12 weeks before recovery of motor function began. Improvement continued over several years. All patients regained functional though dysarthric speech. Three of the four patients are ambulatory, one without assistance. As a few patients make a notable recovery from the locked-in syndrome resulting from ventral pontine infarction, aggressive supportive therapy should be considered in the early months of the syndrome.
- Published
- 1982
- Full Text
- View/download PDF
25. Recovery from the locked-in syndrome.
- Author
-
McCusker EA, Rudick RA, Honch GW, and Griggs RC
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Quadriplegia complications, Vertebrobasilar Insufficiency complications, Mutism complications, Quadriplegia diagnosis
- Published
- 1980
26. Acalculia following a dominant-hemisphere subcortical infarct.
- Author
-
Corbett AJ, McCusker EA, and Davidson OR
- Subjects
- Dominance, Cerebral, Female, Humans, Mathematics, Middle Aged, Neuropsychological Tests, Aphasia etiology, Cerebral Infarction psychology
- Abstract
A 60-year-old, right-handed woman experienced persistent impairment of calculating ability following a subcortical infarct involving the head of the left caudate nucleus, the anterior superior putamen, and the anterior limb of the internal capsule extending superiorly into the periventricular white matter. Acalculia resulted from defects of numerical syntax, the loss of ability to manipulate mathematical concepts, and impaired working memory.
- Published
- 1986
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.