Chapter 6 Pharmacogenetics
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Jeffrey R. Bishop Pharmacogenetics is the study of how genetics influences drug treatment outcomes. Much research has been conducted to identify and characterize gene variants that impact the pharmacokinetic and pharmacodynamic aspects of medications used to treat neurologic and psychiatric disorders. This chapter reviews the current state of pharmacogenetic aspects of these treatments. Medications with supporting pharmacogenetic information in product labeling, clinical guidelines, or important mechanistic implications are discussed. At...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 5 Epigenetic mechanisms underlying nervous system diseases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Irfan A. Qureshi, Mark F. Mehler Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene–gene and gene–environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositionin...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 4 Evolving views of human genetic variation and its relationship to neurologic and psychiatric disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Daniel H. Geschwind Recent advances in exome and genome sequencing in populations are beginning to define the genetic architecture of neurologic and psychiatric disease. At the same time these findings are changing our perspective of genetic variant contributions to disease, implicating both rare and common genetic variation in common diseases. Most of what we know about genetic contributions to disease so far comes from analysis of mutations in protein-coding genes. Since most genetic variation lies in nonprotein-coding regions of the g...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 3 Ethical issues in neurogenetics
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Wendy R. Uhlmann, J. Scott Roberts Many neurogenetic conditions are inherited and therefore diagnosis of a patient will have implications for the patient's relatives and can raise ethical issues. Predictive genetic testing offers asymptomatic relatives the opportunity to determine their risk status for a neurogenetic condition, and professional guidelines emphasize patients’ autonomy and informed, voluntary decision making. Beneficence and nonmaleficence both need to be considered when making decisions about disclosure and nondisclosu...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 2 Genetic and genomic testing for neurologic disease in clinical practice
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Brent L. Fogel The influence of genetics on neurologic disease is broad and it is becoming more common that clinicians are presented with a patient whose disease is likely of genetic origin. In the search for mutations causing Mendelian disorders, advances in genetic testing methodology have propelled modern neurologic practice beyond single-gene testing into the realm of genomic medicine, where routine evaluations encompass hundreds or thousands of genes, or even the entire exome, representing all protein-coding genes in the genome. The...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 1 Clinical approach to the patient with neurogenetic disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Thomas D. Bird, Corrie O. Smith Neurogenetic diseases are surprisingly common. This chapter reviews a systematic approach to the evaluation of a patient thought to have such a disease. The emphasis is on first recognizing potential clues to the diagnosis contained in the family history and presentation of symptoms. Ataxia, neuropathy, muscle weakness, dementia, epilepsy, and cognitive delay are all “reservoirs” of neurogenetic disease. A high index of suspicion for genetic causes and a thoughtful evaluation of simplex (sporadic) cas...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 17 Plexus and peripheral nerve metastasis
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Kelly G. Gwathmey Cancer in the form of solid tumors, leukemia, and lymphoma can infiltrate and metastasize to the peripheral nervous system, including the cranial nerves, nerve roots, cervical, brachial and lumbosacral plexuses, and, rarely, the peripheral nerves. This review discusses the presentation, diagnostic evaluation, and treatment options for metastatic lesions to these components of the peripheral nervous system and is organized based on the anatomic distribution. As skull base metastases (also discussed in Chapter 14) result ...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 16 Management – spinal metastases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Anick Nater, Arjun Sahgal, Michael Fehlings Due to a worldwide increase of cancer incidence and a longer life expectancy of patients with metastatic cancer, a rise in the incidence of symptomatic vertebral metastases has been observed. Metastatic spinal disease is one of the most dreaded complications of cancer as it is not only associated with severe pain, but also with paralysis, sensory loss, sexual dysfunction, urinary and fecal incontinency when the neurologic elements are compressed. Rapid diagnosis and treatment have been shown ...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 15 Epidural and intramedullary spinal metastasis: clinical features and role of fractionated radiotherapy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Dirk Rades, David Schiff Metastases involving the spinal epidural space and cord parenchyma are major sources of neurological impairment and decreased quality of life in cancer patients. Herein we review the clinical manifestations, pathophysiology, importance of early diagnosis and initiation of treatment, and role of fractionated radiotherapy of these disorders. (Source: Handbook of Clinical Neurology)
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 14 Intracranial dural, calvarial, and skull base metastases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Rebecca A. Harrison, Joo Yeon Nam, Shiao-Pei Weathers, Franco DeMonte Metastatic disease to the intracranial dura, the calvarium, and the skull base is relatively uncommon but presents unique diagnostic and management challenges in the patient with cancer. Modern imaging techniques have facilitated the detection of intracranial tumor deposits, leading to increased incidence. While dural and calvarial metastases often present with nonspecific symptoms, skull base metastases present with distinct clinical syndromes dependent on the loca...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 13 Leptomeningeal metastasis
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Sophie Taillibert, Marc C. Chamberlain Leptomeningeal metastasis (LM) results from dissemination of cancer cells to both the leptomeninges (pia and arachnoid) and cerebrospinal fluid (CSF) compartment. Breast cancer, lung cancer, and melanoma are the most common solid tumors that cause LM. Recent approval of more active anticancer therapies has resulted in improvement in survival that is partly responsible for an increased incidence of LM. Neurologic deficits, once manifest, are mostly irreversible, and often have a significant impact o...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 12 Neurocognitive aspects of brain metastasis
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Jeffrey S. Wefel, Michael W. Parsons, Vinai Gondi, Paul D. Brown Brain metastases are common, occurring in approximately 20% of cancer patients. One of the biggest concerns for these patients and their families is neurocognitive decline. Neurocognitive issues in this patient population are complex and many patients have neurocognitive impairment due to systemic therapies even before they develop brain metastases. The development of brain metastases as well as the treatment of these tumors can cause decline in neurocognitive function. ...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 11 Systemic therapy for brain metastases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Vyshak Alva Venur, Vidhya Karivedu, Manmeet S. Ahluwalia Central nervous system metastases cause grave morbidity in patients with advanced malignancies. Lung cancer, breast cancer, and melanoma are the three most common causes of brain metastases. Although the exact incidence of brain metastases is unclear, there appears to be an increasing incidence which has been attributed to longer survival, better control of systemic disease, and better imaging modalities. Until recently surgical resection of solitary or symptomatic brain metastas...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 10 Brain metastases: radiosurgery
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Amparo Wolf, Douglas Kondziolka Stereotactic radiosurgery has revolutionized the management of brain metastases. It delivers focused, highly conformal, ionizing radiation to a tumor delineated using high-resolution imaging, with low toxicity to adjacent brain structures. Randomized controlled and prospective trials have demonstrated a survival advantage and high local control rates after stereotactic radiosurgery for metastatic disease to the central nervous system, including for up to 10 brain metastases. Its minimal-access nature make...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
Chapter 9 Brain metastases: fractionated whole-brain radiotherapy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 149 Author(s): Tony J.C. Wang, Paul D. Brown Brain metastases are the most common malignant adult intracranial tumors, occurring in approximately 10–30% of cancer patients, and generally lead to a poor prognosis. The incidence has been steadily rising, likely due to longer survival from newer systemic therapies and increased utilization of magnetic resonance imaging. Historically, whole-brain radiotherapy has been a standard of care for the management of patients with brain metastases. However, better understanding of both the acute and long-term to...
Source: Handbook of Clinical Neurology - January 5, 2018 Category: Neurology Source Type: research
