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]