In the neurosciences and psychiatry, PET has already shown some useful applications in the understanding of the biochemical processes in cerebral function. Serotoninergic neuron abnormalities have been suggested in neuropsychiatric diseases, and extensive efforts have been made to radiolabel antidepressant drugs which bind to 5-HT sites on the serotoninergic neuron terminals. Most of these compounds have been found so far unsuitable for PET studies, and radiolabelling of a new highly potent serotonin uptake blocker is under investigation.
Currently, the clinical application of PET is used in the following areas of Neurology.
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Evaluation of patients with focal epilepsy
Epilepsy is a clinical condition resulting from excessive, uncontrolled electrical activity in the brain. It is generally acknowledged in the neurology and PET communities that clinical PET in epilepsy is of major significance for the diagnosis and treatment of epileptic patients.
The Austin Hospital Epilepsy Unit is the leading Australian centre which enables comprehensive diagnosis, assessment and management of patients with medically refractory epilepsy.
Clinical role of Positron Emission Tomography in Refractory Focal Epilepsy
Positron emisson tomography has an established role in the localisation of epileptic foci in patients being evaluated for epilepsy surgery. The decision regarding seizure surgery depends on a concordance of data from multiple investigations including video EEG, neuropsychological tests, magnetic resonance imaging, ictal and interictal SPECT and PET.
Temporal Lobe Epilepsy
Extratemporal Epilepsy
The spectrum of focal refractory epilepsy has changed dramatically since PET was first introduced at the Austin Hospital in 1992. With advances in both anatomical and functional neuroimaging, it is now possible to consider patients with extratemporal focal epilepsy for pre-surgical evaluation. The seizures in this group of patients are typically very short-lived and therefore difficult to capture with ictal SPECT which often demonstrates spread beyond the seizure focus by the time the patient has been injected with the blood flow tracer.
These patients often have extremely brief seizures that are has come a greater understanding of focal epilepsy. Although in has been convenient to group the focal epilepsies into temporal and extratemporal, these categories are artifical and all focal epilepsy should be considered.
18F-FDG-PET in Childhood Epilepsy
18F-FDG PET has a limited but definite role in the investigation of children with epilepsy. PET's role includes:
(1) the investigation of children with intractable, non-lesional partial epilepsy where a region of hypometabolism may indicate occult cortical dysplasia.
(2) the investigation of children with intractable partial epilepsy in whom clinical, MR, SPECT and EEG data are discordant or where these studies inadequately define the boundaries of the epileptigonic zone requiring resection.
(3) the investigation of infants with unilateral hemispheric epilepsy syndromes and bilateral clinical or EEG manifestations in whom confirmation of the metabolic and structural integrity of the contralateral hemisphere would allow proceeding to surgery.
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Evaluation of patients with neurodegenerative disorders
An increasing utility of 18F-FDG PET in neurodegenerative conditions has been reported, and the Centre for PET has a prospective evaluation in place to establish the role of 18F-FDG PET in the diagnosis and management of these disorders.
The Austin Hospital has an established neuropsychiatric unit specialising in neurodegenerative disorders. The vast majority of patients referred to this unit have later life cognitive decline and the bulk of these are afflicted with Alzheimer's disease (AD). There is now treatment for AD in the form of tablets which help both symptoms and have some disease slowing effect, and new therapies are being tested in clinical trials. Both of these possibilities argue strongly for diagnostic specificity. Currently clinical assessment is the accepted gold standard, but this is frequently regarded as "subjective" by clinicians. 18F-FDG PET scanning offers an objective confirmation of the clinical impairment by usually showing metabolic deficits in the posterior cortical areas (temporal and parietal) with sparing of the primary cortices. Cerebral SPECT is less often as clearcut in early cases. Early objective confirmation allows patients and their relatives to plan more effectively whilst patients are still medically competent.
Whilst 18F-FDG PET is very useful in AD, it is potentially far more valuable in the non-Alzheimer dementias. There are several major conditions included in this term, which can be grouped pathologically by so-called non-specific superficial cortical degenerative changes (spongiform degeneration and gliosis) which are thought recently to be related to abnormalities of the microtubule associated binding protein, tau. These can occur in different brain regions at onset creating differing clinical presentations. Discrete clinical syndromes have arisen from these differing regional specificities of pathology:
- fronto-temporal dementia (FTD)
- primary progressive aphasia (PPA)
- semantic dementia (SD)
- progressive prosopagnosia (PP)
- progressive visuospatial dysfunction (PVD)
Some of these conditions, particularly PVD, may also be caused by focal AD pathology which is often very hard to differentiate clinically. Functional imaging with 18F-FDG PET may help separate these cases by depicting more extensive metabolic changes in the traditional areas affected by typical AD. In the other conditions, there are frequently extensive metabolic reductions in the regions affected by the pathology helping objectively to confirm the localization of the clinical impairments. If such patterns of hypometabolism are present, they assist in objectively confirming these somewhat unusual diagnoses. Prognosis, insurance & disability claims and services can then be justified with confidence.
Click here to see Clinical Protocols for this topic.
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