Chapter 027. Aphasia, Memory Loss, and Other Focal Cerebral Disorders (Part 8) potx

Chapter 027. Aphasia, Memory Loss, and Other Focal Cerebral Disorders (Part 8) Language in PPA The language impairment in PPA varies from patient to patient. Some patients cannot find the right words to express thoughts; others cannot understand the meaning of heard or seen words; still others cannot name objects in the environment. The language impairment can be fluent (that is, with normal articulation, flow, and number of words per utterance) or nonfluent. The single most common sign of primary progressive aphasia is anomia, manifested by an inability to come up with the right word during conversation and/or an inability to name objects shown by the examiner. Many patients remain in an anomic phase through most of the disease and experience a gradual intensification of word- finding deficits to the point of near-mutism. Others, however, proceed to develop distinct forms of agrammatism and/or word comprehension deficits. The agrammatism consists of inappropriate word order and misuse of small grammatical words. One patient, for example, sent the following e-mail to her daughter: "I will come my house in your car and drive my car into chicago. . . . You will back get your car and my car park in my driveway. Love, Mom." Comprehension deficits, if present, start with an occasional inability to understand single low-frequency words and gradually progress to encompass the comprehension of conversational speech. The impairments of syntax, comprehension, naming, or writing in PPA are no different from those seen in aphasias of cerebrovascular causes. However, they form slightly different patterns. According to a classification proposed by Gorno- Tempini and colleagues, three variants of PPA can be recognized: an agrammatical variant characterized by poor fluency and impaired syntax, a semantic variant characterized by preserved fluency and syntax but poor single word comprehension, and a logopenic variant characterized by preserved syntax and comprehension but frequent word-finding pauses during spontaneous speech. The agrammatical variant is also known as progressive nonfluent aphasia and displays similarities to Broca's aphasia. However, dysarthria is usually absent. The semantic variant of PPA is also known as semantic dementia and displays similarities to Wernicke's aphasia, but the comprehension difficulty tends to be milder. The most obvious difference between aphasias caused by CVA and those caused by neurodegenerative disease is the post-stroke improvement in CVA- related aphasias, leading to a progressive crystallization of the subtypes listed in Table 27-1, versus the gradual deterioration that leads to a loss of syndromic specificity as the disease progresses. Pathophysiology Patients with PPA display progressive atrophy (indicative of neuronal loss), electroencephalographic slowing, decreased blood flow (measured by single photon emission CT) and decreased glucose utilization (measured by positron emission tomography) that are most pronounced within the language network of the brain. The abnormalities may remain confined to left hemisphere perisylvian and anterior temporal cortices for many years. The clinical focality of primary progressive aphasia is thus matched by the anatomic selectivity of the underlying pathologic process. The three variants display overlapping distributions of neuronal loss but the agrammatical variant is most closely associated with atrophy in the anterior parts of the language network (where Broca's area is located), the semantic variant with atrophy in the temporal components of the language network, and the logopenic variant with atrophy in the temporoparietal component of the language network. The relationship between poor language comprehension and damage to Wernicke's area, which is a feature of CVA-related aphasias, is not present in PPA. Instead, poor comprehension is most closely associated with neuronal loss in the lateral and anterior temporal cortex. Neuropathology Approximately 30% of patients have shown the microscopic pathology of Alzheimer's disease, presumably with an atypical distribution of lesions. In the majority of cases, the neuropathology falls within the family of frontotemporal lobar degenerations (FTLD) and displays various combinations of focal neuronal loss, gliosis, tau-positive inclusions, Pick bodies, and tau-negative ubiquitin inclusions (Chap. 365). Familial forms of PPA with tau-negative ubiquinated inclusions have recently been linked to mutations of the progranulin gene on chromosome 17. Apolipoprotein E and prion protein genotyping has shown differences between patients with typical clinical patterns of Alzheimer's disease and those with a diagnosis of PPA. The intriguing possibility has been raised that a personal or family history of dyslexia may be a risk factor for primary progressive aphasia, at least in some patients, suggesting that this disease may arise on a background of genetic or developmental vulnerability affecting language-related areas of the brain.[newpage] . Chapter 027. Aphasia, Memory Loss, and Other Focal Cerebral Disorders (Part 8) Language in PPA The language impairment in PPA varies. frontotemporal lobar degenerations (FTLD) and displays various combinations of focal neuronal loss, gliosis, tau-positive inclusions, Pick bodies, and tau-negative ubiquitin inclusions (Chap point of near-mutism. Others, however, proceed to develop distinct forms of agrammatism and/ or word comprehension deficits. The agrammatism consists of inappropriate word order and misuse of small