Page 883 - Motor Disorders Third Edition

MOTOR SEQUELA OF DEMENTIA / 865
uptake in the caudate and putamen, supports the diagno-
sis of early CBD (37).
The pathology of CBD is characterized by circumscribed
cortical atrophy with spongiosis and ballooned neuron, the
distribution of which correlates with the clinical presenta-
tion. Neuronal and glial tau pathology is extensive in gray
and white matter of the cortex, basal ganglia, diencephalon,
and rostral brainstem, with abnormal tau accumulation in
astrocytes forming pathognomonic astrocytic plaques, the
latter of which is associated with bvFTD, semantic demen-
tia, and progressive nonfluent aphasia. The parkinsonian
syndrome of CBD responds poorly to levodopa, which aids
in differentiating it from idiopathic PD.
NEUROACANTHOCYTOSIS
Irregularly spaced erythrocytes with a thorny surface and
terminal bulbs termed acanthocytes are a valuable clue to the subsequent hepatic and neurologic abnormalities due to
presence of neuroacanthocytosis, a neurodegenerative dis-
order that includes choreoacanthocytosis (ChAc) and the
phenotypically similar disorder, McLeod syndrome, both
of which can be characterized by progressive neurocogni-
tive deficits. Onset of ChAc occurs in the first to seventh
decade with variable generalized weakness, involuntary
movements including grimacing, dystonia, tic-like move-
ments, chorea, and subtle parkinsonism; later neuropsychi-
atric features include subcortical dementia supervene with
cognitive impairment, personality change, and depression.
Other major neurological signs include disturbed coor-
dination, hyporeflexia, seizures, and peripheral neuropathy.
Progressive chorea and dementia resembles Huntington
disease (HD), which should be considered in the differen-
tial diagnosis of ChAc. Brain MRI demonstrates areas of
abnormally increased signal in the caudate and putamen,
and variably in periventricular and hemispheric white mat-
ter, including the corpus callosum (38). Brain FDG-PET
imaging shows dysfunction of dopaminergic neurons in
the ventrolateral substantia nigra, with reduced glucose
metabolism in the basal ganglia (39). The disorder is caused
by homozygous or compound heterozygous mutation at the
9q21.2 locus of the VPS13A gene encoding chorein.
Cognitive and psychiatric impairment occurs late in the
course of McLeod syndrome that displays X-linked inheri-
tance due to mutation at the Xp21.1 locus in the XK gene
that encodes an antigen of the Kell blood group system.
Involvement of the CNS was indicated by the occurrence
of seizures, psychopathology, choreatic movements, and
cognitive impairment, the latter of which was discerned on
assessment of higher cortical function, including psycho-
metric tests that showed abnormal memory and executive
function in 15 of 22 men, age 27 to 72 years, with the diag-
nosis of McLeod neuroacanthocytosis (40).
Brain MRI in 13 patients showed a rim of increased
1T232I--inidtoendsoibtyeninzatmheidlea-tSePraElCpTutaanmdenFDinGf-oPuErTpaimtieangtisn.gBpraeirn-
formed in three patients showed trwedoupcaetdiednotsp,aomneinoef-wDh2-orme-
ceptor binding in the striatum of
had reduction that was more widespread, without any clini-
cal sign of cerebral involvement, and in the absence of a
movement disorder and puantiiemnpt adireemd odnosptraamteidnes-uDb2n-roercmepa-l
tor binding, one other
glucose metabolism of the caudate nuclei.
WILSON DISEASE
Untreated, this autosomal recessive disorder of copper
metabolism, which presents with hepatic, neurologic, and
psychiatric disturbances, alone or in combination, also
manifests subcortical dementia (41). Liver involvement,
which consists of recurrent jaundice, hepatitis, and chronic
liver disease, results from intracellular hepatic copper with
homozygous or compound heterozygous mutation at the
13q14.3 locus of ATP7B gene encoding copper-transport-
ing ATPase 2.
Neurological involvement includes a predominant
movement disorder presenting with tremor, loss of fine
motor control, chorea, choreoathetosis, or a rigid-dystonic
condition with mask-like facies, rigidity, gait disturbance,
and pseudobulbar involvement. Psychiatric disturbances
include depression, neurotic behavior, disorganized per-
sonality and intellectual deterioration.
Kayser-Fleischer rings at the limbus of the cornea are
found in all patients with CNS involvement. Early psycho-
metric studies (42, 43) performed before treatment with a
diet low in copper and pencillamine chelation in patients
with severe motor involvement showed neuropsycho-
logical findings that were so pronounced and, combined
with memory deficits, were consistent with dementia (43,
44). Although many such patients recovered neurological
function and even showed reversible changes in CT imag-
ing (45), one reported patient (46) with advanced WD,
Mini-Mental Status score of b1a2s/a3l0g, aanngdliaT2a-nhdypmeriidnbternaisne
signal abnormalities in the
on MRI before commencement of chelation therapy with
D-penicillamine, was noted to have progressive interim
improvement but died. At postmortem examination there
were WMC noted in the superior frontal gyri extending
into the deep cortex associated with unbound copper,
neuronal loss, capillary proliferation, Alzheimer type 1
and 2 astrocytes, and abundant Opalski cells. The cause
of subcortical dementia in WD is not well understood.
Reversible cerebral dysfunction, which could occur as a
result of hepatic encephalopathy and neurotransmitter