Chapter 8 The highly anxious individual presenting for Huntington disease-predictive genetic testing: the psychiatrist's role in assessment and counseling
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Mark Groves Guidelines in the Huntington disease genetic counseling community have set a standard for the process of at-risk counseling, recommending the involvement of a multidisciplinary team, which includes a psychiatrist or psychologist. Though most studies have been largely reassuring regarding the psychologic consequences of predictive testing, there are individuals presenting to testing who really want something else other than the test results, who are being pressured by others to obtain results, or who remain deeply ambivalent a...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 7 Preclinical motor manifestations of Huntington disease
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Andrew McGarry, Kevin M. Biglan Huntington disease (HD) is an autosomal-dominant, progressive neurodegenerative condition characterized by multiple movement disorders, psychiatric disturbances, and cognitive decline. As an insidious, progressive disorder, clinical phenoconversion in HD can be quite subtle and difficult to pinpoint. In light of this ambiguity, substantial interest has developed in HD research for biomarker identification, with the intent of establishing specific changes or “stages” of disease progression. Presumably,...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 6 Cognitive and behavioral changes in Huntington disease before diagnosis
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Jane S. Paulsen, Amanda C. Miller, Terry Hayes, Emily Shaw Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The ear...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 5 The diagnosis and natural history of Huntington disease
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Fernando Pagan, Yasar Torres-Yaghi, Marcelle Altshuler Huntington disease (HD) is an autosomal-dominant disorder resulting from CAG triplet repeats, which leads to an expanded polyglutamine sequence in the HTT (Huntingtin) protein. Accumulation of the Huntingtin protein ultimately leads to neurodegeneration and negative effects in multiple clinical domains, including motor function, cognition, and behavior. HD is a disorder governed by genetics, and the ability to quantify the CAG triplet repeats can provide important insight regarding...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 4 Statistical modeling of Huntington disease onset
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Tanya P. Garcia, Karen Marder, Yuanjia Wang Huntington disease (HD) is caused by a CAG trinucleotide expansion in the huntingtin gene. We now have the power to predict age-at-onset from subject-specific features like motor and neuroimaging measures. In clinical trials, properly modeling onset age is important, because it improves power calculations and directs clinicians to recruit subjects with certain features. The history of modeling onset, from simple linear and logistic regression to advanced survival models, is discussed. We high...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 3 Epidemiology of Huntington disease
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Chris Kay, Michael R. Hayden, Blair R. Leavitt Huntington disease (HD) is an autosomal-dominant neurologic disorder caused by an expanded CAG trinucleotide repeat mutation in patients with characteristic motor signs and specific brain pathology. A repeat of 36 CAG or more can lead to the disease, with increased penetrance and decreased age of onset at longer CAG repeats. The epidemiology of HD thus depends on ascertainment of individuals with the expanded CAG mutation, and on examination of clinical signs to accurately assess disease o...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 2 Mechanisms underlying neurodegeneration in Huntington disease: applications to novel disease-modifying therapies
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Christopher A. Ross, Martin Kronenbuerger, Wenzhen Duan, Russell L. Margolis The CAG repeat expansion mutation that causes Huntington Disease (HD) was discovered more than 20 years ago, yet no treatment has yet been developed to stop the relentless course of the disease. Nonetheless, substantial progress has been made in understanding HD pathogenesis. We review insights that have been gleaned from HD genetics, metabolism, and pathology; HD mouse and cell models; the structure, function and post-translational modification of normal and...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 1 Genetics of Huntington disease
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Martha A. Nance In this chapter, we review the evolution of our understanding of the genetic aspects of HD, and the applications of our understanding in the management of Huntington's disease patients and families over the last 150 years. Important aspects of the clinical genetics and epidemiology of Huntington's disease are discussed, such as the definition of “normal” and “abnormal” numbers of CAG (cytosine-adenine-guanine) repeats in the critical spot within the huntingtin gene, meiotic instability of CAG repeat numbers, commo...
Source: Handbook of Clinical Neurology - September 25, 2017 Category: Neurology Source Type: research
Chapter 31 Pharmacotherapy for cavernous malformations
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 143 Author(s): Robert F. Rudy, Rose Du Cerebral cavernous malformations, vascular abnormalities comprised of endothelial cells in the absence of connective tissue or muscle, are often epileptogenic and often treated initially with antiepileptic drugs. This chapter discusses the role of pharmacotherapy in managing focal epilepsy secondary to cavernous malformations in adults, children, and pregnant women. Several drugs are available and potentially efficacious in suppressing seizures stemming from cavernous malformations. In addition, antiepileptic pha...
Source: Handbook of Clinical Neurology - May 25, 2017 Category: Neurology Source Type: research
Chapter 30 Spinal cavernous malformations
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 143 Author(s): Aaron J. Clark, Doris D. Wang, Michael T. Lawton Spinal cavernous malformations are rare intramedullary vascular lesions of the central nervous system. Most are located in the thoracic spine. Patients present with either acute neurologic deficit or gradual deterioration. Weakness is the most common presenting symptom. The annual hemorrhage risk is 2.1%. Diagnosis is made by magnetic resonance imaging as these lesions are occult on angiography. Surgical removal is indicated in patients with hemorrhage and neurologic deficit. All lesions...
Source: Handbook of Clinical Neurology - May 25, 2017 Category: Neurology Source Type: research
Chapter 29 Thalamic cavernous malformations
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 143 Author(s): Christina E. Sarris, Gursant S. Atwal, Peter Nakaji Cavernous malformations of the thalamus represent a particularly complex subset of cavernous malformations because of the highly eloquent nature of the involved tissue and their deep location. The decision about whether to operate on any individual lesion depends on the specific location of the lesion within the thalamus, the nature of the patient's symptoms, and the patient's history. When surgery is recommended, the approach must be chosen carefully. Each part of the thalamus is rea...
Source: Handbook of Clinical Neurology - May 25, 2017 Category: Neurology Source Type: research
Chapter 28 Brainstem and cerebellar cavernous malformations
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 143 Author(s): Gursant S. Atwal, Christina E. Sarris, Robert F. Spetzler Cavernous malformations are vascular lesions that occur throughout the central nervous system, most commonly in the supratentorial location, with brainstem and cerebellar cavernous malformations occurring more rarely. Cavernous malformations are associated with developmental venous anomalies that occur sporadically or in familial form. Patients with a cavernous malformation can present with headaches, seizures, sensorimotor disturbances, or focal neurologic deficits based on the...
Source: Handbook of Clinical Neurology - May 25, 2017 Category: Neurology Source Type: research
Chapter 27 Supratentorial cavernous malformations
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 143 Author(s): Jason A. Ellis, Daniel L. Barrow Supratentorial cavernous malformations are uncommon cerebral vascular lesions that may present many unique challenges for treating physicians. The vast majority will be discovered during workup for seizures or after symptomatic intracerebral hemorrhage. Supratentorial cavernous malformations are increasingly being discovered incidentally in patients who obtain brain imaging for unrelated reasons. Management strategies including watchful waiting, antiepileptic drug therapy, microsurgery, or an expanding a...
Source: Handbook of Clinical Neurology - May 25, 2017 Category: Neurology Source Type: research
Chapter 26 Developmental venous anomalies
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 143 Author(s): Michael A. Mooney, Joseph M. Zabramski Developmental venous anomalies (DVAs) are relatively common lesions, present in up to 3% of the population. The defining characteristic of these lesions is the confluence of radially oriented veins into a single dilated venous channel. DVAs are also known as cerebral venous angiomas, cerebral venous malformations, and cerebral venous medullary malformations. They are the most common type of cerebral vascular malformation found on autopsy studies, and they are often encountered as incidental finding...
Source: Handbook of Clinical Neurology - May 25, 2017 Category: Neurology Source Type: research
Chapter 25 Pathology of cavernous malformations
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 143 Author(s): Efrem M. Cox, Nicholas C. Bambakidis, Mark L. Cohen Cavernous malformations (CMs) are low-pressure angiographically occult lesions, composed of blood-filled sinusoidal locules known as “caverns.” Although these lesions were once believed to be congenital in nature, there is compelling evidence to support de novo formation of CMs as well. They can occur as sporadic lesions or be inherited in an autosomal-dominant phenotype in familial forms of the disease. The pathophysiology of CMs is commonly believed to be due to abnormal vascula...
Source: Handbook of Clinical Neurology - May 25, 2017 Category: Neurology Source Type: research
