Porth's Essentials of Pathophysiology, 4e

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Disorders of Brain Function

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OtherTypes of Dementia Cerebrovascular injury, brain tissue atrophy, alcohol- ism, and genetic disorders can also result in dementia. Vascular Dementia Vascular dementia is caused by brain injury resulting from ischemic or hemorrhagic damage. Vascular demen- tia is the second most common cause of cognitive impair- ment in the elderly. The incidence is closely associated with hypertension, but also with arrhythmias, stroke, peripheral vascular disease, lipid abnormalities, and dia- betes mellitus. 73–75 The usual onset is between the ages of 55 and 70 years, and more men are affected than women. The vessel disorders associated with vascular dementia include atherosclerosis, small vessel disease, cerebral amy- loid angiopathy, brain infarcts, and cerebral hemorrhage. In addition to the impact of cerebral vascular lesions on dementia, the association between Alzheimer disease and vascular dementia points to a possible pathogenic link between AD and blood vessel causes of dementia. Slowness in psychomotor functioning is a main clini- cal feature of this dementia, and symptoms of depression are present in up to 60% of patients with this disease. 4 The onset may be gradual or abrupt, the course usually is a stepwise progression, and there are focal neurologic symptoms related to local areas of infarction. Frontotemporal Dementia Frontotemporal dementia (FTD) refers to a group of disorders associated with atrophy of the frontal and anterior temporal lobes of the brain. 76,77 Originally known as Pick disease, FTD now refers to a syndrome that includes primary progressive aphasia, cortico- basal degeneration, progressive supranuclear palsy, and semantic dementias. The disease often begins between 45 and 64 years of age, and is one of the most common forms of dementia in persons younger than 65 years. The pathophysiology of FTD is not well understood. The disease is characterized by extensive atrophy of the frontotemporal regions, with the involved cortex being severely depleted of neurons. Most recently, mutations of the prograndin gene on chromosome 17 have been associated with intranuclear inclusions found in the brain tissue of persons with the disorder. Prograndin is a growth factor with multiple functions, including neuronal survival. Other than mutations linked to chromosome 17, several other chromosomes have been implicated in FTD, including mutations in chromosomes 3 and 9. There are two distinct clinical presentations of FTD: behavior and language. The former is more common, with behavioral presentations of disinhibited and impul- sive actions or apathy, with inappropriate social behav- ior. Unlike Alzheimer disease, which usually begins with memory difficulties, FTD begins with very disruptive behaviors that can be quite extreme, and can be misdi- agnosed as schizophrenia or psychotic depression. The second type of FTD behavior involves disturbances in understanding or expressing language.

Diagnosis of FTD is based on evidence of cognitive impairment and exclusion of other illnesses that cause cognitive and behavioral deficits. Neuroimaging can be helpful in distinguishing FTD from other types of cogni- tive disorders. Typically, structural imaging shows ante- rior temporal and frontal lobe atrophy. There is no specific cure for FTD. Treatment is focused on symptom management and support for patients, fam- ilies, and caregivers. Current research focuses on molec- ular biology to better understand the underlying disease and the potential for identification of novel treatments, particularly disease-modifying treatments. Wernicke-Korsakoff Syndrome Wernicke-Korsakoff syndrome most commonly results from chronic alcoholism. Wernicke disease is charac- terized by acute weakness and paralysis of the extra- ocular muscles, nystagmus, ataxia, and confusion. 4 The affected person also may have signs of peripheral neu- ropathy. The person has an unsteady gait and complains of diplopia. There may be signs attributable to alcohol withdrawal such as delirium, confusion, and hallucina- tions. This disorder is caused by a deficiency of thiamine (vitamin B 12 ), which directly interferes with produc- tion of glucose, the brain’s main nutrient. Many of the symptoms are reversed when nutrition is improved with supplemental thiamine. The Korsakoff component of the syndrome involves the chronic phase with severe impairment of recent memory. There often is difficulty in dealing with abstrac- tions, and the person’s capacity to learn is defective. Confabulation (i.e., recitation of imaginary experiences to fill in gaps in memory) probably is the most distinc- tive feature of the disease. Polyneuritis also is common. Unlike Wernicke disease, Korsakoff psychosis does not improve significantly with treatment. Huntington Disease Huntington disease (HD) is a hereditary disorder char- acterized by chronic progressive chorea, psychological changes, and dementia. 1,4,78–81 Although the disease is inherited as an autosomal dominant disorder, the age of onset most commonly is in the fourth and fifth decades. By the time the disease has been diagnosed, the person often has passed the gene on to his or her children. Approximately 10% of HD cases are juvenile onset. 80 Children with the disease rarely live to adulthood. Huntington disease is caused by a polyglutamine trinucleotide repeat expansion in the HD gene. The HD gene, located on chromosome 4, encodes a protein known as huntingtin . 1,78–80 Normal HD genes contain 6 to 35 copies of the trinucleotide repeat; an expan- sion of repeats beyond this level is associated with dis- ease. There is an inverse relationship between repeat number and age of onset, such that longer repeats are associated with earlier onset. Repeat expansions occur during spermatogenesis, so that paternal transmission is associated with early onset in the next generation. Although the biologic function of normal huntingtin remains unknown, there is little evidence to suggest