Page 881 - Motor Disorders Third Edition
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pyramidal reactions in up to one-half of patients due to MOTOR SEQUELA OF DEMENTIA / 863
loss of substantia nigra dopaminergic neurons and the
failure orefsuppo-nrseegutolatthioennoigfrpoostsrt-iastyanladpetfiiccisttrainadtatlhDe2 recep- one-half of patients having an affected first-degree relative.
tors in neuro- About 30 to 50% of FTD cases are familial with mutations
leptic challenge (21). The atypical neuroleptic clozapine, at the 17q21.31 loci of the MAPT gene encoding tau, and
which exerts its antipsychotic effects via the D4 receptors, the GRN gene encoding progranulin (25). Most patients
is generally better tolerated and low doses are sufficient for have evidence of grasp, snout, and sucking reflex frontal
symptom control. The diagnosis of DLB should be con- release signs; however, motor neuron signs can accompany
sidered in patients with suspected idiopathic Parkinson clinical syndromes of FTLD-TDP characterized by TDP43
disease who develop psychotic symptoms in response to ubiquitin-positive inclusions. The presence of TDP43-pos-
anti-parkinsonian agents. itive inclusions as the major disease protein in ubiquitin-
positive, tau-, and a-synuclein-negative FTLD and ALS
PARKINSON DISEASE DEMENTIA (26) suggests a common pathologic substrate linking these
neurodegenerative disorders (27).
About 10 to 40% of patients with PD develop dementia
(PDD) and a large number of such patients develop mild The bvFTD type of FTLD, known as Pick disease, is asso-
cognitive impairment. About 15% to 20% of patients in ciated with a dramatic change in personality and social con-
movement disorders clinics, and a quarter of those in one duct, with apathy, loss of volition, social disinhibition and
autopsy series diagnosed with idiopathic PD, had another distractibility, and preservation of memory. Both PNFA
neurodegenerative condition such as AD (22). Since the and SD, previously known as primary progressive aphasia,
pathology of PDD and DLB is similar, the clinical des- are associated with significant language difficulties.
ignation should conform to the arbitrary one year rule
that Parkinsonian features should antedate dementia by All three lack a significant spatial disorder as manifested
more than a year to evoke the diagnosis of PDD, whereas by intact diagram copying and dot counting, and intact per-
dementia 12 months after onset of parkinsonism, instead ception, as tested by naming challenges, functional object
suggests DLB. Clues to accurate diagnosis include the descriptions, and pantomime object use. Patients with FTD
presence of rest tremor seen in 90% of patients. The occur- perform poorly on tests of frontal lobe function, including
rence of PDD is associated with a worse prognosis and a the Wisconsin card sort, Stroop and trail-making tests.
less favorable response to anti-parkinsonian medication
than PD without dementia. Brain neuroimaging employing MRI, FDG-PET, and
SPECT demonstrate concordant atrophy and abnormal
Autosomal dominant progressive frontotemporal tracer uptake in frontal and anterior temporal cortices of
dementia (FTLD) and parkinsonism due to mutation at the either hemisphere, which may be bilaterally symmetric or
17q21.31 locus of the microtubule-associated protein tau asymmetric and affect the left or right hemisphere dispropor-
(MAPT) gene leads to disinhibition, apathy, poor impulse tionately. The slowing of the background often seen on EEG
control, psychosis, alcoholism, dystonia, eye movement in AD is not generally seen in the FTLD syndromes. Asym-
abnormalities, eyelid opening and closing apraxia, and metric atrophy of the left frontal and temporal lobes is seen
upper and lower motor neuron dysfunction (23). Neu- in forms of PNFA and SD associated with symmetrical atro-
ropathological features include tau-positive cytoplasmic phy of bilateral anterior temporal neocortex and inferior and
inclusions and ballooned neurons in some, but not all kin- middle temporal gyri. Microscopically, all forms of FTLD are
dred. PDD may be treated with the available anti-cholines- associated with microvacuolar change without specific histo-
terase medication (24). logical features and severe astrocytic gliosis with or without
ballooned cells and Pick-type inclusions. There are currently
FRONTOTEMPORAL LOBE DEMENTIA no effective treatments for the FTLD syndromes.
Patients with frontotemporal lobe dementia (FTLD) have VASCULAR DEMENTIA
selective, although differential involvement of frontal and
temporal lobe cortices, depending on the type of FTLD. Of The vascular dementias (VaD) are heterogeneous disor-
the three types of FTLD, the most common is behavioral ders encompassing lesions due to embolism, hemorrhage,
variant frontotemporal dementia (bvFTD), followed by and ischemia, affecting vessels of differing caliber, large
semantic dementia (SD) and progressive non-fluent apha- and small, named and unnamed, with involvement of
sia (PNFA). Onset is generally before age 65 with nearly cortical and subcortical structures. Strategic large vessel
strokes of the right posterior cerebral artery and anterior
cerebral artery territories can result in a clinical dementia,
as may single lacunes in the genu of the capsule, intralam-
inar thalamic nuclei, and head of the caudate. Subcortical
ischemic VaD due to lacunar infarction and periventricu-
