Frontotemporal Dementia
Frontotemporal dementia, also called frontal lobe degeneration or
non-specific frontal lobe dementia, has a slow, insidious onset marked
in the early stages by personality changes, then progressive loss of
speech (fluent or nonfluent aphasia), apathy, and finally mutism.
Changes can include impulsive behaviors and disinhibition, poor insight
into consquences of behavior, repetitive behaviors, loss of personal
hygiene, and loss of social graces. The mean age of onset is in the 6th
decade. About 90% of cases are sporadic and the rest familial. The
gross pathologic findings are similar to Pick disease, with marked
atrophy in a frontal lobe and sometimes temporal lobe distribution.
Microscopically, there is a spongy vacuolization of layer 2 of the frontal
and temporal cortex, along with loss of neurons and gliosis, and no
increase in neuritic plaques. Pick bodies may appear in 15% of cases.
Some cases have been linked to mutations in the tau gene.
Aggregates of tau protein are not common in sporadic cases. Both
straight filaments and neurofibrillary tangles with paired helical
filaments of mutant tau protein have been found in familial cases.
(Arvanitakis, 2010)
Huntington Disease
This is autosomal dominant in inheritance and the patient's usually
present between the ages of 20 and 50 years, with a course that
averages 15 years to death. Patients may either present with
choreiform movements, character change, or psychotic behavior. The
genetic defect is localized to chromosome 4. The abnormal gene,
called HD, on chromosome 4 encodes for a protein, called huntingtin,
that contains increased trinucleotide CAG repeat sequences.
Individuals without the disease have 26 repeats or less; persons with
27 to 35 repeats are generally unaffected themselves but may transmit
the disease to offspring. More than 40 CAG repeats is present in over
99% of cases. The greater the number of repeats, the earlier the onset
of the disease. Spontanenous new mutations are uncommon. (Levin et
al, 2006)
Pathologically there is severe loss of small spiny neurons in the
caudate and putamen with subsequent astrocytosis. With the loss of
cells, the head of the caudate becomes shrunken and there is "ex
vacuo" dilatation of the anterior horns of the lateral ventricles. There is
a loss of gamma aminobutyric acid (GABA), acetylcholine and
substance P. (Purdon et al, 1994)