Second edition

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340 Neurodegenerative and movement disorders
to treatment with an antidepressant, and a selective serotonin
reuptake inhibitor (SSRI; e.g., escitalopram), given
their tolerability, should receive consideration. Insomnia
may, of course, be part of a depressive syndrome and, as
such, may eventually respond to treatment with an antidepressant;
in cases in which a hypnotic is required, consideration
may be given to melatonin or zolpidem. Apathy
in Alzheimer’s disease, as discussed in Section 6.2, may
respond to methylphenidate. Agitation, as discussed in
Section 6.4, may respond to risperidone or olanzapine; in
my opinion it is reasonable to begin with a low dose of
risperidone (e.g., 0.25–0.5 mg/day) and to titrate it slowly
and carefully. Although quetiapine has been associated
with sedation, in my experience this agent, if started at a
low dose (e.g., 6.25–12.5 mg) and titrated very carefully,
may be extremely useful. With regard to the use of
antipsychotics, concern has been raised that they may
accelerate cognitive decline; however, at least in the case
of risperidone, this does not appear to be the case
(Livingston et al. 2007). Carbamazepine, as pointed out in
Section 6.4, is also effective for agitation, although the sideeffect
burden of this agent may give one pause. Delusions
and hallucinations, whether accompanied by agitation or
not, may respond to the same antipsychotics as used for
agitation; however, as with all symptoms, one must be
sure that these delusions or hallucinations are sufficiently
troubling to warrant the risk attendant on the use of
antipsychotics.
8.2 PICK’S DISEASE
Pick’s disease, first described by the neuropsychiatrist
Arnold Pick in 1892 (Pick 1892), is a rare cause of dementia
in which the dementia is distinguished by its presentation
with a personality change of the frontal lobe type or by
a more or less complete Kluver–Bucy syndrome; it is probably
equally common in men and women.
Before proceeding with this discussion, it is necessary to
mention nomenclature. Pick’s disease has been welldescribed,
both clinically and pathologically, for about a
century. More recently it has become apparent that a fairly
large number of different pathologic entities may cause a
similar clinical picture, and some authors have recommended
grouping all of these disorders together with
Pick’s disease, with different authors suggesting different
names for the resulting collection: some have proposed the
term ‘Pick complex’, whereas others favor ‘frontotemporal
dementia’. In this area of uncertain nomenclature, it is my
opinion that we should preserve Pick’s disease as an independent
entity while leaving these newer disorders with
similar clinical presentations provisionally grouped under
the rubric of frontotemporal dementia until, with further
work, they become clearly differentiated, both clinically
and pathologically, at which time they may be regarded as
independent entities on their own.
Clinical features
The onset is gradual and insidious, typically occurring in
the fourth through the seventh decades; onsets as young as
21 (Lowenberg et al. 1939) or 25 (Coleman et al. 2002)
years of age have, however, been noted. In most cases, the
presentation is with a personality change, typically of the
frontal lobe type, with disinhibition, coarsening of behavior,
and perseveration (Bouton 1940; Ferraro and Jervis
1936; Litvan et al. 1997a; Mendez et al. 1993; Munoz et al.
1993; Munoz-Garcia and Ludwin 1984; Nichols and
Weigner 1938); elements of the Kluver–Bucy syndrome,
such as hyperorality and hypersexuality, are also common
(Cummings and Duchen 1981; Mendez et al. 1993; Munoz
et al. 1993; Munoz-Garcia and Ludwin 1984). Some
patients may also be prone to restless wandering; however,
in contrast to patients with Alzheimer’s disease, who tend
to wander off and get lost, patients with Pick’s disease tend
to get back to their starting point (Mendez et al. 1993;
Munoz et al. 1993). Eventually, cognitive deficits appear,
such as short-term memory loss, concreteness, and difficulty
with calculations; in many cases an aphasia, typically
of the expressive type, will supervene, and, in a small
minority, seizures may occur.
Rarely, Pick’s disease may present with a slowly progressive
aphasia (Graff-Radford et al. 1990; Kertesz et al. 1994;
Knibb et al. 2006; Wechsler et al. 1982), amnesia (Wisniewski
et al. 1972), or apraxia (Fukui et al. 1996).
Computed tomography or MR scanning reveals lobar
atrophy (Knopman et al. 1989; Wechsler et al. 1982), typically
affecting the frontal and anterior temporal lobes; in
some cases the atrophy is so severe as to present a ‘knifeblade’
appearance.
Course
Pick’s disease is relentlessly progressive, leading to a profound
dementia with death within 5–10 years (Robertson
et al. 1958), generally from an intercurrent pneumonia.
Etiology
Pick’s disease is an example of ‘lobar’ atrophy, with the
frontal and temporal lobes bearing the brunt of the disease
process. Interestingly, even when the temporal lobes are
very hard hit, the posterior two-thirds of the superior temporal
gyrus is generally spared, often to a remarkable
degree, as illustrated in Figure 8.3. Although in most cases
both the frontal and the temporal lobes are clearly affected,
in a minority only one lobe will be macroscopically abnormal
(Sjorgen et al. 1952). Microscopically one sees widespread
neuronal loss and gliosis. Pick cells (large, ballooned
neurons) and Pick bodies (rounded or oval argentophilic
intracytoplasmic inclusions) may be seen in affected areas;
the Pick bodies are composed of neurofilaments that are