Frontotemporal Dementias Without Tau Pathology

Some cases with clinical and pathologic findings involving these brain regions do not show evidence of Tau deposition. Some cases with this pattern are found in association with motor

neuron disease (see below); in this setting, Tau-negative, ubiquitin-positive inclusions can be found in superficial cortical layers in temporal and frontal lobe and in the dentate gyrus.

This pattern of pathology is termed motor neuron disease inclusion dementia. It has also been described in the absence of ALS-like pathology. Other cases show no specific inclusions

but rather have cortical atrophy and some thalamic gliosis. This pattern of injury has been termed dementia lacking distinctive histology (DLDH). [172] With time and increased

biochemical and molecular investigations, these unusual entities are likely to be reclassified.

Vascular Dementia

It is now clear from autopsy studies of individuals who were carefully studied during life that various types of vascular injury to the brain can result in dementia.[173] Some individuals

with a rapidly progressive cognitive decline have vasculitis (discussed above) and will often show improvement with treatment. Among the irreversible disorders, several specific entities

have been identified, which can be separated in part by their clinical course (typically a stepwise progression rather than a gradual decline) and imaging features. Various etiologies

include small areas of infarction (granular atrophy from cortical microinfarcts, multiple lacunar infarcts, cortical laminar necrosis associated with reduced perfusion/oxygenation) and

diffuse white matter injury (Binswanger disease, CADASIL). Additionally, dementia has been associated with so-called strategic infarcts, which are usually embolic and involve brain

regions such as the hippocampus, dorsomedial thalamus, or frontal cortex including cingulate gyrus. Many individuals, in fact, will demonstrate a combination of pathologic changes.

There is also an interaction between vascular injury and other dementing disorders, such as AD. It has been found that patients with vascular changes above a certain threshold have a

lower burden of plaques and tangles for their level of cognitive impairment than do those without vascular-based cerebral pathology.[174]

DEGENERATIVE DISEASES OF BASAL GANGLIA AND BRAINSTEM

Diseases affecting these regions of the brain are frequently associated with movement disorders, including rigidity, abnormal posturing, and chorea. In general, they can be categorized

as manifesting either a reduction of voluntary movement or an abundance of involuntary movement. The basal ganglia and especially the nigrostriatal pathway play an important role in

the system of positive and negative regulatory synaptic pathways that serve to modulate feedback from the thalamus to the motor cortex. The most important disorders in this group are

those associated with parkinsonism and Huntington chorea.

Parkinsonism

Parkinsonism is a clinical syndrome characterized by diminished facial expression, stooped posture, slowness of voluntary movement, festinating gait (progressively shortened,

accelerated steps), rigidity, and a "pill-rolling" tremor. This type of motor disturbance is seen in a number of conditions that have in common damage to the nigrostriatal dopaminergic

system. Parkinsonism may also be induced by drugs that affect this system, particularly dopamine antagonists and toxins. The principal diseases to be discussed here that involve the

nigrostriatal system are as follows:

• Parkinson disease (PD)

• Multiple system atrophy, a disorder that may have parkinsonism as a prominent symptom (clinical presentation as striatonigral degeneration) as well as other symptoms

(cerebellar ataxia and autonomic dysfunction)

• Postencephalitic parkinsonism, which was observed in the wake of the influenza pandemic that occurred between 1914 and 1918 and is now vanishingly rare

• Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), which are movement disorders that may also exhibit cognitive impairment; they share some

pathologic and genetic features with each other and with other tauopathies (see the discussion above in the section on frontotemporal dementias).

Parkinson Disease

This diagnosis is made in patients with progressive parkinsonism in the absence of a toxic or other known underlying etiology. Familial forms with autosomal-dominant or autosomalrecessive

inheritance exist. Although these make up a limited number of cases, they have contributed to our understanding of the pathogenesis of the disease. In addition to the

movement disorder, there are other, less well-characterized changes in mental function, which may include dementia, in a subset of individuals with PD.

Morphology.

On pathologic examination, the typical macroscopic findings are pallor of the substantia nigra( Fig. 28-37 ) and locus ceruleus. On microscopic examination, there is loss of the

pigmented, catecholaminergic neurons in these regions associated with gliosis. Lewy bodies ( Fig. 28-37C ) may be found in some of the remaining neurons.

Figure 28-37Parkinson disease (PD). A, Normal substantia nigra. B, Depigmented substantia nigra in idiopathic PD. C, Lewy bodies in a substantia nigra neuron stain bright pink. (C,

courtesy of Dr. R. Kim, V.A. Medical Center, Long Beach, CA.)

Figure 28-38Huntington disease (HD). Normal hemisphere on the left compared with the hemisphere with HD on the right showing atrophy of the striatum and ventricular dilation.

(Courtesy of Dr. J.-P. Vonsattel, Columbia University, New York, NY.)

TABLE 28-3-- Spinocerebellar Ataxias

Date: 2016-04-22; view: 710