Page 882 - Motor Disorders Third Edition
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864 / chapter 57 CORTICOBASAL DEGENERATION
lar leukoariosis spares U fibers as in Binswanger disease.
Autosomal dominant cerebral arteriopathy with subcor- Corticobasal degeneration (CBD) is a rare progressive neu-
tical infarcts and leukoencephalopathy (CADASIL) due rodegenerative 4-repeat (4R) tauopathy that presents in the
to heterozygous mutation at the 19p13.12 locus of the fifth to seventh decades of life with basal ganglia and cortical
NOTCH3 gene is characterized clinically by relapsing involvement, including with parkinsonism, akinesia, and
strokes with neuropsychiatric symptoms in young adults rigidity, accompanied by other basal ganglia and cortical
of both sexes. dysfunction, including limb and oculomotor apraxia, corti-
cal sensory loss, dystonic posturing, myoclonus, and alien
Three criteria for the clinical diagnosis of VaD include limb phenomenon (33). Other motor signs include blep-
cognitive loss, cerebrovascular etiopathogenesis inferred herospasm, hypomimia, dysarthria, orofacial dyspraxia,
by history, examination, and neuroimaging; and onset of gait disorder, choreoathetosis, postural instability, percus-
dementia within three months of a symptomatic stroke, the sion myoclonus, and action and postural tremor with a fre-
latter criterion of which is not necessary for the diagnosis quency of 6 to 8 Hz that is more irregular and jerkier than
of subacute VaD. Clinical and motor manifestations vary the rest tremor of PD. The arm is the most affected region
depending on the site of the lesion. in choreoathetosis and assumes an adducted shoulder and
flexed elbow and wrist position. Eye movement abnor-
A careful history may reveal memory loss antedating malities include bilateral horizontal saccades with slowed
the stroke in up to 15% of patients, suggesting underly- extraocular movements appearing to require multiple steps
ing AD inheritance worsened by stroke. Neuroimaging to reach a target, with normal vertical saccades that differ-
characterizes cerebral small vessel disease, such as lacu- entiate the condition from progressive supranuclear palsy
nar infarcts and white matter changes (WMC), appear- (PSP). Depression occurs commonly in CBD followed by
ing as bilateral areas of confluent symmetric hyperintense apathy, irritability, and agitation. Delusions and obsessive-
uheatmedispinhvereircsiosingnraelcochvearnygesseqounenTc2e-ws eoinghbterdai,nfluMidR-Ia,ttaennd- compulsive behavior are less common.
hypodense periventricular or subcortical areas on brain Formal cognitive and neuropsychological testing shows
CT (28). The Leukoaraiosis and Disability (LADIS) study particular affliction of executive function, with better per-
collaboration, which showed an association between the formance on tests of immediate recall and attention in CBD
severity of baseline WMC and transition to disability in a as compared to tests of praxis, digit span, and unimanual
cohort of elderly patients, showed progression to demen- and bimanual motor series, which are more pronounced in
tia in 15%, and cognitive impairment without dementia patients with AD and extrapyramidal disease. Recognition
in 25% so studied, independent of age, education, and memory is generally spared, however there may be impair-
medial temporal atrophy (29). Binswanger-related sub- ment of coding and recall strategies.
cortical pathology, found in up to one-third of normal Distinctive patterns of atrophy on brain neuroimaging
subjects of age 65 years and older and in one-half of those have been observed in patients with autopsy-confirmed CBD
with AD, has been characterized as a silent epidemic (30). (34). To1-fwceoirgthicteadl volumetric MRI showed predominant pat-
The presence of one or more lacunes increases the risk for terns atrophy involving the posterior inferior,
AD by 20-fold and reduces the plaque and tangle burden middle, and superior frontal lobes, the superior premotor
required for clinical signs to appear. The importance of the cortex, and the posterior temporal and parietal lobes com-
vascular component in dementia needs to be specifically pared to controls. Other areas of atrophy included insular
recognized and treated. Patients with AD and seemingly cortex, the supplemental motor area, subcortical grey matter
trivial vascular lesions warrant treatment to control cere- (GM) of the globus pallidus, putamen, head of the caudate,
brovascular risk factors and to promote stroke prevention. and a small region of the brainstem at the dorsal pontomed-
Antihypertensive therapy is associated with a 28% reduc- ullary junction. White matter atrophy was additionally noted
tion in the risk of recurrent stroke and a 38 to 55% reduc- in the posterior frontal lobes at the corticomedullary junc-
tion in the risk of dementia (31), and may actually delay tion and corpus callosum, involvement of the latter of which
the development of clinical dementia in those with patho- correlated well with impaired cognition (35).
logical signs of the disease. Brain FDG-PET imaging shows global reduction of
oxygen and glucose metabolism in the cerebral hemi-
Acetylcholinesterase inhibitor medication is useful in sphere contralateral to the most affected limb, and in the
the management of VaD (32), and all the available cholin- thalamus concordant with nigrostriatal dopaminergic
esterase agents approved for the treatment of AD have been dysfunction (36). A pattern of asymmetrically reduced
efficacious in treating patients with VaD. Calcium channel frontoparietal cerebral cortical metabolism and cerebral
blockers may benefit VaD and AD by improving calcium
dysregulation and conferring neuroprotection.
blood flow, in conjunction with bilaterally reduced F-dopa
