Sunday, April 22, 2007

Natural history of primary progressive aphasia

Rhun EL et al.Neurology 2005; 65:887-891.
49 patients were diagnosed (France). median age at onset was 62. First visit median age 66. Impaired ADL's occurred within 7 years. 75 % eventually met diagnostic criteria for FTD, 14 % for LBD, 8 % for CBD, 60 % died after median 7 years.

Primary progressive aphasia

Review article Mesulam M-M. Primary progressive aphasia- a language based dementia. NEJM 2003;349-1535-42
Salient points
1. Language only disorder can be present for up to 14 years, or if other deficits are present the language deficit is "salient feature." Complex hobbies such as gardening, sculpting, painting may remain intact. One patient flew his airplane.
2. Differentiate from pure progressive dysarthria or phonologic disintegration (disruption of the formation of words rather than their use); from AD; from FTD with or without AD.
3. "Semantic dementia" refers to patients with a combination of impaired word comprehension and impaired recognition (agnosia) of faces and objects.
4. Clinical picture may vary. "Some patients cannot find the words to express their thoughts. Others cannot understand the meaning of words either seen or heard. Still others cannot name objects. The language can be fluent or nonfluent. (whereas) Alzheimer's disease it is almost always fluent." Some patients may have preserved ability to write language.
5. Anomia is almost always first, later patients may develop agrammatism or develop comprehension problems almost to the point of mutism.
6. Functional imaging has shown greater activation of traditional nonlanguage areas (compensatory areas) during the performance of language tasks.
7. E4 allele is not associated with ppa
8. Chromosome 17 carries the tau gene and is linked to frontotemporal lobar atrophies (Picks or dementia without distinctive histopathology). PPA and frontal lobe dementia may represent anatomically distinct manifestations of a unitary spectrum of degenerative brain diseases. A specific haplotype *H1) of tau gene is overrepresented in patients with the sporadic form of PPA.
9. Pathology of FT degeneration is lobar atrophy, neuronal loss, ubiquitin positive inclusions, tauopathy, occassionally taking the form of Pick bodies.
10. A recent report of 3/4 sibs and 0/12 members of parental generation affected raises the possibility of an aut recessive form of tau-opathy.
11. Voice synthesizers and other technology based devices are useful.