Examination and Test Findings

On cognitive examination, patients with FTD will characteristically show executive dysfunction. Various office or bedside tests will reveal perseveration, stimulus-boundedness, and problems with planning, sequencing, and organization. When asked to interpret proverbs, or when given pairs of objects and asked to find the objects' similarities and differences, FTD patients will show an impairment in abstraction abilities. Attentional impairment is also seen.

The neurological examination may reveal primitive reflexes, that is, frontal release signs. These reflexes include the snout, suck, root, palmomental (chin contraction to hand irritation), and grasp reflexes. Parkinsonism and signs consistent with motor neuron disease may also be seen. Asymmetry is sometimes noted in the physical findings in patients with FTD.

Basic laboratory studies and the EEG will be unrevealing. Structural neuroimaging (CT or MRI) can demonstrate atrophy of the frontal and/or temporal lobes. Functional neuroimaging will demonstrate hypoperfusion/hypometabolism in the frontal and/or temporal lobes. Asymmetry can be seen.

A neuropsychological evaluation can confirm the presence of cognitive dysfunction as noted above. The evaluation should include tests of executive function and cognitive flexibility as impairment in these areas is a key characteristic of FTD. Memory testing can clarify whether reported memory problems are characteristic of FTD or of the PPA or SD variants. In addition, language testing can be used to detect the nonfluent language disturbance in PPA or the fluent aphasia and loss of word meaning in SD. Finally, assessment of visuospatial skills can help differentiate FTD from AD and other dementing disorders in which these abilities decline.

Neuropathology. On gross anatomical examination, the brain of an FTD patient will characteristically show atrophy of the frontal lobes, anterior temporal lobes, and/or striatum (see Fig. 15.4). On microscopic examination, approximately 60 percent of FTD patients will be found to have microvacuolar-type pathology. In brains with microvacuolar pathology, loss of neurons and spongiform changes in the superficial

neuropil are noted. Of FTD patients 25 percent have the Pick type of FTD with loss of neurons, gliosis, and tau- and ubiquitin-positive inclusions in neurons. Other pathologies seen in FTD patients include Pick changes associated with motor neuron disease and progressive subcortical gliosis; cases of FTD not associated with clear pathological changes have also been recognized (Snowden et al., 2002).

The cognitive/behavioral picture seen in patients with FTD correlates with the anatomical pattern of disease. Patients with the disinhibited form of FTD usually have pathological changes in the orbitofrontal cortex and anterior temporal lobes. The apathetic form of FTD is usually associated with pathology in the dorsolateral frontal cortex. Patients with the stereotypic form of FTD usually have prominent disease in the striatum and temporal lobes. FTD patients with prominent changes in social behavior usually have a predominance of disease in the right hemisphere. Patients with the SD variant of FTD characteristically have temporal lobe disease. Patients with PPA have disease in the left-hemisphere language circuit, and patients with primary progressive apraxia characteristically have frontoparietal disease. While the clinical syndrome correlates with the anatomical pattern of disease in patients with FTD, it usually does not predict histological type (Snowden et al., 2002).

Neurochemistry. Abnormalities of the serotonergic system have been documented in FTD. A 40 percent decrease in the number of serotonergic neurons has been demonstrated in brainstem serotonergic nuclei (Yang and Schmitt, 2001). Decreased serotonin receptor binding has been demonstrated in the frontal and temporal cortices as well as the hypothalamus (Swartz et al., 1997). Impairment in the nigrostriatal dopaminergic system has been reported in FTD (Rinne et al., 2002). Excitatory amino acid AMPA receptors are decreased in number in the frontal and temporal cortices in FTD patients and may be differentially decreased in various pathological subtypes of FTD (Procter, 1999). Multiple studies of the cholinergic system in FTD have failed to demonstrate an abnormality of cholinergic functioning. The locus ceruleus is likewise spared in FTD.

0 0

Post a comment