Nadine Dougall

Single photon emission tomography with 99mTc-exametazime in major depression and the pattern of brain activity underlying the psychotic/neurotic continuum.

Forty patients with a major depressive episode were investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, an intravenous ligand taken into brain in proportion to regional cerebral blood flow, thereby providing an estimate of regional metabolism. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. They also completed a range of neuropsychological tests. They were compared with 20 control subjects matched for age, gender, premorbid intelligence and education. The uptake of 99mTc-exametazime was expressed for a range of anatomically defined regions of interest relative to calcarine/occipital cortex. The depressed group showed reduced uptake in the majority of cortical and sub-cortical regions examined, most significantly in temporal, inferior frontal and parietal areas. Unexpectedly, there was a strong positive association between uptake and scores on the Newcastle scale, especially in cingulate areas and frontal cortex. After removing the variance attributable to the Newcastle ratings, however, there emerged the expected negative association between Hamilton scores and anterior tracer uptake. The associations between neuropsychological impairment and regional brain uptake of tracer in part reflected the pattern seen with the Newcastle scale: for example, impairment of memory function correlated with higher uptake into posterior cingulate areas. We propose that depressive illness may be characterised by two processes. One leads to an overall reduction in anterior neocortical function, perhaps related to symptom severity. The other mechanism is manifest as relatively increased function, most notably within cingulate and frontal areas of the cerebral cortex in association with psychotic symptoms. The findings offer new understanding of the brain states underlying depressive illness and a potential focus to subsequent neuropharmacological analysis.

State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment

Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.

Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake.

BACKGROUND For a quantitative comparison of images obtained during (99m)Tc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i.e., global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization. METHODS Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs. RESULTS The reduction of cerebral blood flow in the group of ATD patients appeared 1.7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone. CONCLUSION An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.

Short-term effects of electroconvulsive treatment on the uptake of99mTc-Exametazime into brain in major depression shown with single photon emission tomography

Fifteen patients with major depression who were being treated with bilateral electroconvulsive treatment (ECT) were investigated before and 45 min after a single ECT using split-dose Single Photon Emission Tomography (SPET or SPECT) with 99mTc-Exametazime. All patients suffered from unipolar depressive illness and were rated on the Newcastle scale and with the 17-item Hamilton scale. They completed tests of orientation and verbal memory on the day of ECT. For comparison, verbal memory was also tested on the preceding day. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Significant decreases in tracer uptake were confined to the inferior anterior cingulate cortex. The changes were correlated with the severity of depressive symptoms and more weakly with decrements of memory function produced by ECT; there was no significant correlation with stimulus intensity or electroencephalographic measures of seizure duration.

Regional cerebral blood flow in IDDM patients: effects of diabetes and of recurrent severe hypoglycaemia.

SummaryChronic hyperglycaemia and recurrent severe hypoglycaemia have both been implicated as causing cerebral damage in patients with diabetes. Although cognitive dysfunction and intellectual impairment have been demonstrated in patients with recurrent severe hypoglycaemia, structural correlates have not been described, and it is not known whether specific functional changes occur in the brains of affected patients. Regional cerebral blood flow was estimated by SPECT with 99mTechnetium Exametazime in 20 patients with IDDM. Ten patients had never experienced severe hypoglycaemia and 10 had a history of recurrent severe hypoglycaemia. Patient results were compared with 20 age- and sex-matched healthy volunteers. We observed differences between the two patient groups and the control group. Tracer uptake was greater in diabetic patients in the superior pre-frontal cortex. This effect was particularly pronounced in the group who had a history of previous severe hypoglycaemia. Patients with a history of recurrent hypoglycaemia also had a relative reduction in tracer uptake to the calcarine cortex. This suggests an alteration in the pattern of baseline regional cerebral blood flow in diabetic patients with frontal excess and relative posterior reduction in cerebral blood flow.

Clonidine infusion increases uptake of 99mTc-Exametazime in anterior cingulate cortex in Korsakoff's psychosis.

The effects upon regional brain function of infusing either saline or clonidine (1.5 microgram/kg) has been examined in 18 patients with alcoholic Korsakoffs psychosis using 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO or 99mTc-Exametazime) and Single Photon Emission Tomography (SPET or SPECT). The hypothesis tested was that frontal lobe function would be increased by adrenoceptor stimulation. This was confirmed by an increase in the uptake of 99mTc-Exametazime into anterior cingulate regions of the frontal lobes. Patients were scanned before and after saline or clonidine infusion during performance of a verbal fluency task. There was a significantly increased performance of verbal fluency in patients given clonidine. This effect was variable and could not be unequivocably distinguished from increases in performance in the saline treated group. Nevertheless, the increase in neuropsychological performance was also correlated with increased function in left dorsolateral frontal cortex within the clonidine treated group. An exploratory examination of other brain areas suggested that relative increases in posterior cingulate cortex and changes in the symmetry of function within the thalamus may also be produced by acute infusion of clonidine in Korsakoff patients. The findings support the idea that adrenergic mechanisms may modulate cognitive performance by actions on attentional systems within the brain. These appear to be located primarily within limbic cortex. It is, of course, notable that this can occur in patients with profound and disabling amnesia.

Uptake of 99mTc-exametazime shown by single photon emission computerized tomography in obsessive-compulsive disorder compared with major depression and normal controls.

Twelve patients with obsessive‐compulsive disorder (OCD) were investigated at rest using single photon emission computerized tomography with 99mTc‐exametazime. The uptake of 99mTc‐exametazime was expressed relative to calcarine/occipital cortex. Patients were matched for drug treatment with 12 patients with a major depressive episode and the patient groups were compared with a control group. Significant bilateral decreases in tracer uptake were confined to basal ganglia in the OCD group. There was a paradoxical positive correlation between anxiety ratings and tracer uptake to basal ganglia in the OCD group. The findings confirm that the functional topography of OCD implicates altered function in the basal ganglia.

PASAT performance and the pattern of uptake of 99mTc-exametazime in brain estimated with single photon emission tomography.

The effect of the paced auditory serial addition test (PASAT) on the regional uptake of 99mTc-exametazime was determined by single photon emission computed tomography. Twenty insulin-treated diabetic outpatients were scanned at rest and during the performance of the PASAT task using split-dose injection of tracer. When resting and activation scans were compared there were significant decreases in tracer uptake in the right anterior cingulate and left posterior cingulate areas during PASAT activation. The findings are compared with previous studies which had implicated the anterior cingulate area in the mechanisms of attention in humans and other animals. The potentially confounding role of anxiety during attentional tasks is discussed.

The effect of anxiety induction on the regional uptake of 99mTc-exametazime in simple phobia as shown by single photon emission tomography (SPET).

Ten patients suffering from DSM-III-R simple phobia were studied under two conditions: (a) while listening to a 4 min relaxation tape, and (b) while listening to a 4 min audio tape describing exposure to the phobic stimulus. During each condition, subjects were injected with 99mTc-Exametazime, a marker of regional cerebral blood flow. Subjective and psychophysiological measures indicated a marked effect of the anxiety induction procedure. Ratio analysis of the SPET data revealed reductions in tracer uptake largely confined to posterior cerebral regions bilaterally. Analysis of brain regions of interest normalised to the whole brain slice showed reductions confined to right temporal/occipital regions. In general there was no clear association between subjective and physiological variables and changes in regional uptake of tracer as a consequence of the anxiety induction procedure. The changes in tracer uptake were dissimilar to those previously reported for other cognitive activation paradigms, providing some reassurance that those functional brain changes were not artefacts of non-specific changes in state anxiety. These posterior brain changes may reflect alterations in activation of the GABA/benzodiazepine complex.

The epidemiology of hospital treated traumatic brain injury in Scotland

BackgroundTraumatic Brain Injury (TBI) is an important global public health problem made all the more important by the increased likelihood of disability following a hospital admission for TBI. Understanding those groups most at risk will help inform interventions designed to prevent causes of TBI, such as falls prevention measures. This study identifies the rate of hospitalisation episodes of TBI in Scotland, explores causes of TBI admissions, and trends in hospitalisation episodes by age and gender over a twelve year period using routinely collected hospital data.MethodsA retrospective analysis of routine hospital episode data identified records relating to TBI for the twelve years between 1998 and 2009. Descriptive and joinpoint regression analysis were used, average annual percentage changes (AAPC) and annual percentage change (APC) in rates were calculated.ResultsBetween 1998 and 2009 there were 208,195 recorded episodes of continuous hospital care in Scotland as a result of TBI. Almost half (47%) of all TBIs were the result of falls, with marked peaks observed in the very young and the oldest groups. The AAPC of hospitalization episode rates over the study period for boys and girls aged 0-14 were -4.9% (95% CI -3.5 to-6.3) and -4.7% (95% CI -2.6 to -6.8) respectively. This reduction was not observed in older age groups. In women aged 65 and over there was an APC of 3.9% (95% CI 1.2 to 6.6) between 2004 and 2009.ConclusionsHospitalisation for TBI is relatively common in Scotland. The rise in the age-adjusted rate of hospitalisation episodes observed in older people indicates that reduction of TBI should be a public health priority in countries with an ageing population. Public health interventions such as falls prevention measures are well advised and evaluations of such interventions should consider including TBI hospitalisation as an alternative or supplementary outcome measure to fractured neck of femur. Further research is needed to advance understanding of the associations of risk factors with increased incidence of TBI hospital episodes in the elderly population.