Porth's Essentials of Pathophysiology, 4e

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Nervous System

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that the disease is caused by an insufficiency related to the mutated gene. Rather, the expansion of the poly- glutamine region of the HD gene seems to bestow a toxic gain of function on the protein. 1 Huntington disease produces localized death of brain cells. The first and most severely affected neu- rons are those of the basal ganglia that modulate motor output. These neurons normally function to dampen motor activity; thus, their degeneration in HD results in increased motor output, often manifested as choreiform movements. Although chorea is the prototypical movement disorder, the full spectrum of motor impairment in HD includes eye movement dis- orders, myoclonus, ataxia, dysarthria and dysphagia, and spasticity. Depression and personality changes are the most common early psychological manifestations; memory loss often is accompanied by impulsive behav- ior, moodiness, antisocial behavior, and a tendency toward emotional outbursts. Persons with HD uni- versally go through cognitive decline, mental slowing, and impaired problem-solving abilities, and eventually become demented. Cognitive decline also heralds the juvenile onset of HD. There is no cure for Huntington disease. The treat- ment is largely symptomatic. Drugs may be used to treat the dyskinesias and behavioral disturbances. Genetic testing can predict whether a person will develop the disease. ■■ Cognition refers to all the processes by which sensory input is transformed, reduced, elaborated, stored, recovered, and used. ■■ Dementia represents a syndrome of deterioration in cognitive function severe enough to interfere with occupational or social performance.The most common cause of dementia is Alzheimer disease, an insidious and progressive disorder that begins with memory impairment and terminates in an inability to recognize family or friends and the loss of control over bodily functions. ■■ Other forms of dementia include vascular dementia due brain injury resulting from ischemic or hemorrhagic damage; frontotemporal dementia with atrophy of the frontal and temporal lobes; Wernicke- Korsakoff syndrome most often resulting from chronic alcoholism; and Huntington disease, a hereditary disorder characterized by chronic and progressive chorea, psychological changes, and dementia. SUMMARY CONCEPTS

R E V I EW E X E R C I S E S 1. A 20-year-old man who was an unbelted driver involved in a motor vehicle accident presents in coma. A. What are the clinical signs of coma? B. What areas of the brain are involved in coma? C. Which complications of traumatic head injury might lead to coma? D. What are the key treatment options to manage elevated intracranial pressure? 2. A 65-year-old woman presents with a 1-hour history of right-sided weakness and aphasia. An immediate CT scan of the brain is negative. A. Where in the brain is the pathology? B. What are the indications to administer intravenous tissue plasminogen activator? C. What are the possible causes of stroke, and what diagnostic tests would reveal the cause? 3. A child is taken to the emergency department with lethargy, fever, and a stiff neck on examination. A. What findings on initial lumbar puncture indicate bacterial versus viral meningitis? B. In the case of bacterial meningitis, what are the most likely organisms, and which antibiotics should be started? 4. A 60-year-old man develops involuntary shaking of his right arm that spreads to the face, after which he collapses with whole-body shaking and loss of consciousness. After 1 minute, the shaking stops and he is confused and disoriented. A. What type of seizure is suggested by the clinical manifestations? B. Assuming this is his first seizure, what diagnostic tests should be performed to identify a cause for the seizure? C. If he has a long history of similar recurrent seizures, what treatments should be instituted? What treatments should be considered if he has failed multiple adequate trials of anticonvulsant medications? R E F E R E N C E S 1. Frosch MP, Anthony D, DeGirofami U. The central nervous system. In: Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran Pathologic Basis of Disease . 8th ed. Philadelphia, PA: Elsevier Saunders; 2010:1279–1344. 2. Hall JE. Guyton & Hall Textbook of Medical Physiology . 12th ed. Philadelphia, PA: Saunders Elsevier; 2011:742–750. 3. Harukuni I, Bhardwaj A. Mechanisms of brain injury after global cerebral ischemia. Neurol Clin. 2006;24:1–21.