Second edition

08.qxd 3/10/08 9:38 AM Page 341
Figure 8.3 Sparing of the posterior two-thirds of the superior
temporal gyrus relative to the frontal lobe and the rest of the
temporal lobe in a case of Pick’s disease. (Reproduced from
Graham and Lantos 1996.)
straight or twisted (Murayama et al. 1990; Rewcastle and
Ball 1968; Zhukareva et al. 2002).
Although most cases of Pick’s disease are sporadic
(Malamud and Waggoner 1943), hereditary cases do occur
(Groen and Endtz 1982; Heston et al. 1987) and are usually
consistent with dominant inheritance (Sjorgen et al. 1952).
Most of these familial cases are associated with mutations
in the tau gene (Bronner et al. 2005; Neumann et al. 2001;
Pickering-Brown et al. 2000); however, a case has also been
reported secondary to a mutation in presenilin-1
(Dermaut et al. 2004).
Differential diagnosis
Both Pick’s disease (Litvan et al. 1997a) and frontotemporal
dementia are distinguished from most other
dementing disorders by their presentation with a personality
change; at present, a reliable differentiation of Pick’s
and frontotemporal dementia from each other on clinical
grounds may not be possible. Tumors of the frontal or
temporal lobes may mimic these disorders, but are immediately
identified by imaging.
Treatment
The general treatment of dementia is discussed in Section
5.1, of the frontal lobe syndrome in Section 7.2, and of the
Kluver–Bucy syndrome in Section 4.12. There is no specific
treatment for Pick’s disease itself.
8.3 FRONTOTEMPORAL DEMENTIA
At the outset it must be recognized that, with regard
to frontotemporal dementia, there is considerable confusion
8.3 Frontotemporal dementia 341
regarding nomenclature. To begin with it must be emphasized
that the term ‘frontotemporal dementia’ refers not to a
discrete disease but rather to a syndrome that in turn results
from multiple different diseases. The syndrome itself, as
noted below, is characterized initially by a personality
change, with, in most cases, the eventual development of a
dementia. As noted in the discussion of Pick’s disease,
some authors would subsume Pick’s disease under the
rubric of frontotemporal dementia; however, in my opinion
this represents inappropriate ‘lumping’ and in this text
Pick’s disease is treated as a disease in its own right (see
Section 8.2). As noted in the section on etiology below,
recent work has begun to identify some of the specific disease
entities responsible for frontotemporal dementia, and it
is hoped that, with further study, our understanding of
these will mature to the point where they are as
well-described as Pick’s disease and thus eventually merit
sections in their own right. Frontotemporal dementia,
among the neurodegenerative disorders, is a relatively common
cause of dementia.
Clinical features
The onset is insidious and generally in the sixth decade.
Clinically (Heutink et al. 1997; Mann et al. 1993a; Neary
et al. 1998), a personality change is usually the first sign of
the disease, and, depending on the kind of personality
change present, one may speak of a ‘frontal variant’ frontotemporal
dementia or a ‘temporal variant’ frontotemporal
dementia.
The frontal variant, as might be expected, is characterized
by the frontal lobe syndrome, with varying mixtures of
disinhibition, mood changes, perseveration, and overall
coarsening of behavior; some patients may become quite
gluttonous and some will show a pronounced taste
for sweets. In some cases the environmental dependency
syndrome may occur; as discussed in Section 4.11,
such patients may compulsively utilize objects that come
into view.
The temporal variant, in turn, is characterized by elements
of the Kluver–Bucy syndrome (with hypersexuality
and hyperorality, wherein patients will eat or drink almost
anything, including, in one case, coffee grounds or banana
peels [Edwards-Lee et al. 1997]) and by ritualistic and
compulsive behaviors, which may include collecting or
hoarding things. Patients with the temporal variant may
also exhibit an anomia, and in such cases the term ‘semantic
dementia’ is often used (Davies et al. 2005).
Over time, and well after the personality change has
become established, a dementia supervenes, which, however,
may remain relatively mild. Judgment and abstract
thinking fail, and eventually there may be amnestic features.
Over time, many patients will also develop an
expressive aphasia (Neary et al. 1993; Snowden et al. 1992);
gradually, this aphasia worsens, gathers receptive elements,
and finally leads to mutism.