ACCURATE DIAGNOSIS OF FRONTOTEMPORAL LOBAR DEGENERATION IS FEASIBLE
AN FRANCISCO, CA — Using a combination of currently available clinical, neuropsychological, and imaging tools, accurate diagnosis of frontotemporal lobar degeneration (FTLD) is feasible, according to a study presented at the last AAN meeting show.
“Many physicians have been taught, and hardcore scientific literature still suggests, that diagnosis of FTLD is difficult,” said chief investigator David S. Knopman, MD, Professor of Neurology at the Mayo Clinic College of Medicine in Rochester, MN. “But our findings show that is not correct – it is feasible.”
That said, diagnosis in some patients presents a challenge as “people with FTLD can seem similar to those with Alzheimer disease,” he said. The authors found that PET or single photon emission computed tomography (SPECT) increases the likelihood of accurate diagnosis.
FTLD is the umbrella term that now applies to the spectrum of neuropathological disorders that previously went under the name of Pick disease, Dr. Knopman said. Typically striking the late middle-aged and the elderly, FTLD is associated with problems of frontal lobe function such as foresight, judgment, and planning, he said. Language can also be affected, with some patients developing nonfluent aphasia or semantic disorders in which they can't remember the meaning of words and objects.
For the study, the researchers reviewed all 433 brains autopsied at the Mayo Alzheimer Disease Research Center Brain Bank from 1993 to 2003; 27 cases with a neuropathological diagnosis of FTLD were identified. Neuropathological criteria for FTLD included the presence of Pick bodies, swollen neurons and tufted astrocytes, dementia lacking distinctive histology – with or without ubiquitin-positive inclusions – and dementia with neuropathological features of motor neuron disease, Dr. Knopman reported.
“We then went back and examined the clinical diagnoses that these 27 people had been given in life to determine the clinical accuracy of those diagnoses,” he said. Of the 27, 22 had been diagnosed with an FTLD syndrome in life, translating to a sensitivity of 81 percent, the study showed.
Of the five who were not diagnosed correctly during life, “a few were diagnosed with dementia but not specifically FTLD,” he said. Specifically, two were thought to have Alzheimer disease, one had vascular dementia, and two were difficult to classify.
Of the 396 cases that were not diagnosed as FTLD postmortem, only one patient had been clinically diagnosed with an FTLD during life, yielding a specificity of 99 percent, the study showed. “The specificity is excellent, the sensitivity, good but not perfect,” Dr. Knopman said.
The clinical diagnosis of FTLD was based on a combination of clinical information, neuropsychological testing, and imaging studies, he said. The neuropsychological testing included standard tests of language, memory, visual-spatial skills, and executive function.
In retrospect, 16 of the 27 (59 percent) cases with a neuropathological diagnosis of FTLD at autopsy had neuropsychological profiles that were diagnostic of FTLD, Dr. Knopman reported. As for imaging, MRI contributed to the certainty of the diagnosis in 16 (59 percent) cases, he said. On MRI, patients with FTLD generally exhibit atrophy that is most prominent in the frontal and temporal lobes; ventricles may be enlarged, and the head of the caudate may be atrophic.
Although PET and SPECT were not performed systematically, these modalities did contribute to diagnostic certainty in the subset of patients for whom the MRI was not diagnostic, Dr. Knopman said. In total, five of the patients had diagnostic SPECTs and one had a diagnostic PET, he said.
“If an FTLD is strongly suspected and the MRI is not diagnostic, PET or SPECT is appropriate,” he said.
IMPORTANCE OF IMAGING
David A. Bennett, MD, Director of the Rush Alzheimer Disease Center and Professor of Neurological Science at Rush University Medical Center in Chicago, IL, agreed. “There are cases where PET and SPECT imaging is legitimate and perhaps even necessary,” he told Neurology Today. “It is sometimes not clinically clear if we are looking at a frontal lobe presentation of Alzheimer disease or FTLD. Imaging can help you make the distinction.”
As for the bigger picture, “Dr. Knopman provides us with the pathological evidence that what many of us think is actually true,” Dr. Bennett said. “FTLD is a difficult diagnosis, but also a feasible one.”
Dr. Knopman noted that with the ongoing development of new neurological therapies, some which someday may specifically target FTLD, correct diagnosis will be increasingly important.
ARTICLE IN BRIEF
✓ Dr. David S. Knopman reported that PET or single photon emission computed tomography (SPECT) – in combination with clinical and neuropsychological tests – can increase the likelihood of accurately diagnosing frontotemporal lobar degeneration.
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