André Dobbeleir

Cognitive and affective disturbances following focal cerebellar damage in adults: a neuropsychological and SPECT study

The traditional view on cerebellar functioning has recently been challenged by results from neuroanatomical, neuroimaging and clinical studies. In this contribution, eighteen patients with primary cerebellar lesions (vascular: n=13; neoplastic: n=5) were systematically investigated by means of an extensive neuropsychological test battery. Fifteen patients (83%) presented with a broad variety of cognitive and linguistic deficits following cerebellar damage. Disturbances of attention (72%), executive functioning (50%) and memory (50%) were most commonly found. Analyses of our results tend to support the hypothesis of a lateralization of cognitive modulation within the cerebellum, the right cerebellar hemisphere being associated with logical reasoning and language processing and the left cerebellum mediating right-hemispheric functions including attentional and visuo-spatial skills. In addition, nine patients (50%) presented with frontal-like behavioural and affective alterations. In an attempt to determine the working-mechanism underlying cerebellar-induced cognitive and affective disturbances, all patients were investigated by means of quantified Tc-99m-ethylenecysteine dimer (ECD) single photon emission computerized tomography (SPECT) studies. From a semiological point of view, damage to the cerebellum can cause a broad spectrum of clinically significant cognitive and affective disturbances. From a pathophysiological point of view, quantified SPECT data, reflecting the phenomenon of cerebello-cerebral diaschisis, support the functional impact of the cerebellar lesion on cortical functioning through disruption of cerebello-cerebral connections.

Measurement of separate kidney clearance by means of 99mTc-DTPA complex and a scintillation camera

A new radioisotopic method of determining the separate glomerular clearance of the kidneys is described. After injection of 99mTc-DTPA, the data from a scintillation camera are recorded by computer. The renal curves are corrected for extrarenal activity and the plasma curve is obtained from a precordial curve. At each instant the slope of the renal curve divided by the corresponding plasma concentration gives the separate clearance value, in the period extending from 80 to 180 s after injection of the tracer. The error and correction factors introduced are discussed. Normal values are established on 25 patients and correspond to inulin clearance values. Left kidney: 60 ml/min (SD=13). Right kidney: 57 ml/min (SD=12). The method is simple for the patient, takes only 20 min, is not dangerous, is particularly applicable to young children and can be repeated frequently in the same patient.

A simple method for measuring separate glomerular filtration rate using a single injection of 99mTc-DTPA and the scintillation camera

A new technique for measuring glomerular filtration in each kidney has been developed using a scintillation camera and the 99mTc-DTPA complex. The technique has been applied to 101 children with various uropathies. Correlations with the total and separate creatinine clearance, the HgCl2 uptake test, and the maximal urinary concentration have been good. The reproducibility of the method has been satisfactory in a small number of patients. The test is particularly adapted to children because of its simplicity, reduced trauma, short duration (20 minutes) and low-radiation dose. In contrast to some other radioisotope techniques, it can be carried out in infants.

Validation of the cerebellum as a reference region for SPECT quantification in patients suffering from dementia of the Alzheimer type

In longitudinal brain studies of dementia of the Alzheimer type (DAT), the cerebellum is often used as a reference region for single photon emission computed tomography (SPECT) quantification, which assumes no significant regional influence of physiological fluctuations or pathology. With the use of absolute quantification in DAT patients, reproducibility of cerebellar uptake of technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) was tested and compared with the mean absolute cerebellar tracer uptake value in DAT patients and healthy control subjects. In 13 DAT patients SPECT studies were repeated within 2 weeks to assess reproducibility of cerebellar regional brain uptake (rBU). With calibrated point sources as scaling factors, cerebellar activity was expressed as rBU of HMPAO per cm3 brain tissue in percent of the injected lipophilic dose of 740 MBq (20 mCi). Also, mean cerebellar rBU in patients suffering from DAT was calculated and compared with a previously established database obtained in healthy volunteers. Repeated SPECT studies within a 2-week interval in clinically stable patients resulted in a mean rBU increase of 6.8 +/- 10.3% in the second SPECT study as compared with the first. A similar shift was previously reported in healthy volunteers. Mean cortical cerebellar rBU values in DAT patients and in the healthy reference population concurred, after cumulative corrections for body surface and for a mean brain volume of 1350 ml (obtained in healthy control subjects), showing respective mean values of 53.9 +/- 7.4 and of 52.0 +/- 7.3 x 10(-6) of the injected lipophilic dose 740 MBq (20 mCi) of HMPAO per cm3 of brain tissue. A unidirectional shift in mean absolute cerebellar uptake values occurs between repeat SPECT examinations in DAT patients similar to previous findings in a group of healthy volunteers. The origin of this phenomenon remains elusive but deserves further study with regard to SPECT (semi)quantification in DAT patients. Most interestingly, the presented findings suggest that with the use of HMPAO SPECT in DAT patients the cerebellum remains scintigraphically uninvolved.

Serotonin 2A receptor, serotonin transporter and dopamine transporter alterations in dogs with compulsive behaviour as a promising model for human obsessive-compulsive disorder

Neuro-imaging studies have shown altered, yet often inconsistent, serotonergic and dopaminergic neurotransmission in patients with obsessive-compulsive disorder (OCD). We investigated both serotonergic and dopaminergic neurotransmission in 9 drug-naïve dogs with compulsive behaviour, as a potential model for human OCD. Single photon emission computed tomography was used with (123)I-R91150 and (123)I-FP-CIT, in combination with (99m)Tc-ECD brain perfusion co-registration, to measure the serotonin (5-HT) 2A receptor, dopamine transporter (DAT) and serotonin transporter (SERT) availability. Fifteen normally behaving dogs were used as reference group. Significantly lower 5-HT2A receptor radioligand availability in frontal and temporal cortices (bilateral) was observed. Further, in 78% of the compulsive dogs abnormal DAT ratios in left and right striatum were demonstrated. Interestingly, both increased and decreased DAT ratios were observed. Finally, significantly lower subcortical perfusion and (hypo)thalamic SERT availability were observed in the compulsive dogs. This study provides evidence for imbalanced serotonergic and dopaminergic pathways in the pathophysiology of compulsions in dogs. The similarities with the altered neurotransmission in human OCD provide construct validity for this non-induced, natural canine model, suggesting its usefulness for future investigations of the pathophysiology of human OCD as well as the effectiveness of psychopharmacological interventions.

The impact of HF-rTMS treatment on serotonin2A receptors in unipolar melancholic depression

BACKGROUND Currently, the underlying neurobiological mechanism as to how repetitive transcranial magnetic stimulation (rTMS) can alter depressive states remains unclear. Animal data suggest that its influence could occur at the neurotransmitter level, such as modulation of the serotonin system. METHODS Twenty-one antidepressant-free medication-resistant unipolar depressed patients, and 21 age- and gender-matched healthy subjects were studied. We examined the neurobiologic impact of 10 high-frequent (HF)-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC) on postsynaptic 5-HT(2A) receptor binding indices (BI) measured with ¹²³I-5-I-R91150 single photon emission computed tomography (SPECT) only in patients. RESULTS Compared with the control group, patients displayed significantly less bilateral dorsolateral prefrontal cortical and significantly higher left hippocampal baseline 5-HT(2A) receptor BI. Successful HF-rTMS treatment correlated positively with 5-HT(2A) receptor BI in the DLPFC bilaterally and correlated negatively with right hippocampal 5-HT(2A) receptor uptake values. CONCLUSIONS Our results indicate that HF-rTMS treatment affect the serotonergic system. Our data also suggest that this kind of treatment affects 5-HT(2A) receptor BI in the DLPFC and in the hippocampus in different ways.

The effect of medetomidine on the regional cerebral blood flow in dogs measured using Technetium-99m-Ethyl Cysteinate Dimer SPECT

Sedatives and anaesthetics are known to cause changes in the regional cerebral blood flow. In dogs intramuscular sedation with medetomidine, a potent sedative frequently used in veterinary medicine, is sometimes indicated prior to intravenous injection of (99m)Technetium-Ethyl Cysteinate Dimer ((99m)Tc-ECD) in brain perfusion studies using Single Photon Emission Computed Tomography (SPECT). Based on the knowledge of the distribution of alpha(2)-receptors in the brain, we hypothesized altered regional brain perfusion in dogs receiving medetomidine prior to (99m)Tc-ECD. Two conditions were compared in 10 dogs; tracer injection before and after intramuscular sedation with medetomidine. In our study, medetomidine caused a significantly higher tracer uptake in all brain regions. Semi-quantification of brain perfusion rendered a lower perfusion index in the subcortical region and an imbalance between left and right cortical perfusion induced by medetomidine. This study shows that caution is needed when quantifying the brain perfusion indices under medetomidine sedation.

Effect of mild mental stress on solid phase gastric emptying in healthy subjects

SummaryRadionuclide gastric emptying studies are performed in clinical routine but the possible influence of the mental state of the patient is never taken into account. We wanted to evaluate the effect of a mild psychological stress on solid phase gastric emptying in healthy young male volunteers. The standard meal consisted of a pancake (500 kj) without additional liquid. Simultaneous dynamic acquisitions of gastric activity in anterior and posterior projection were taken during 90 min starting from the onset of the meal. Gastric emptying was evaluated three times in basal conditions and once under mental stress. Stress was induced by means of a dichotomous listening test, lasting for 30 min, starting at the end of the meal. The results of rest and stress studies were compared. Mild mental stress has a significant influence on gastric emptying. The lag phase increased from 11±3 min to 36±10 min (mean±S.D.) (p < 0.005) and the gastric emptying rate from 79±13%/hour to 100±31%/hour (mean±S.D.) (not significant). During a stress period gastric emptying as a whole is delayed but this is mainly due to the prolongation of the lag phase. Our data also suggest that during the stress period gastric emptying is interrupted and reactivated once the stress period has ended.

Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders

The serotonergic system is disturbed in different mood and affective disorders, with especially the serotonin (5-HT) 2A receptor involved in impulsive aggressiveness and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT 2A receptor in dogs with different behavioural disorders. Three groups of drug naive dogs were studied: 22 dogs showing impulsive aggressive behaviour, 22 showing normal behaviour, and 22 showing anxious behaviour. The serotonin 2A receptor was evaluated with Single Photon Emission Computed Tomography (SPECT) and the serotonin 2A receptor-selective radiopharmaceutical (123)I-R91150. A serotonin 2A receptor binding index (BI), proportional to the cortical receptor density, was calculated. A receiver operating characteristic (ROC) analysis was performed to determine cut-off values at which optimal sensitivity and specificity are achieved and to evaluate the general performance of the BI in reflecting the state of the dog, i.e., impulsive aggressive, normal or anxious. Significantly (P<0.0056) altered 5-HT 2A receptor binding indices were found in bilateral frontal, temporal and occipital cortical brain areas of the dogs behaving abnormally, with consistently increased BI in impulsive aggressive dogs and decreased BI in anxious dogs. These results provide clear evidence for a disturbed serotonergic balance in canine impulsive aggression and anxiety disorders. A right frontal cut-off value of ≥1.92 with 86.4% sensitivity and 2.3% (1-specificity) was obtained for the impulsive aggressive dogs. Differentiating the anxious dogs from the rest of the population was possible with a cut-off value of ≤1.73 with 86.4% sensitivity and 18.2% (1-specificity). We conclude that SPECT imaging with the radioligand (123)I-R91150 can be a helpful tool in evaluating the involvement of the serotonin 2A receptor in the complex mechanisms of impulsive aggressive and anxious behaviour. The 5HT-2A binding index of the right frontal cortex appears to be a valid biomarker in differentiating the studied canine behavioural disorders.

Can severely impaired cortical transit predict which children with pelvi-ureteric junction stenosis detected antenatally might benefit from pyeloplasty?

IntroductionUntil recently, renogram, performed in children with pelvi-ureteric junction stenosis detected antenatally, has not been able to predict the probability of function improvement after surgery or the risk of function deterioration in case of conservative attitude. Recently, Schlotmann et al. have suggested that cortical transit might have this predictive role. The aim of this study, focused on those kidneys with severely impaired cortical transit, was to verify this statement. MethodsAll renograms performed in children during a 3-year period (n=729) were retrospectively reviewed and 19 pediatric patients were selected based on an antenatally detected unilateral pelvi-ureteric junction syndrome, the existence of at least two renograms during the follow-up and a severe cortical transit impairment, visually defined. Twenty-six pairs of data could be analyzed and allowed comparing preoperative and postoperative differential renal function (DRF), and the DRF changes during the conservative management. ResultsAmong the 16 patients who underwent pyeloplasty, 10 showed a significant DRF improvement. Among the 10 patients with conservative follow-up, four showed a significant DRF deterioration. ConclusionSeverely impaired cortical transit seems to be a valuable marker of those patients who could benefit from a pyeloplasty, either because of the high probability of postoperative DRF improvement, or because of DRF deterioration in case of an conservative approach. However, a normal cortical transit, as defined in this study, does not exclude the risk of DRF deterioration. Alternatively, the design of this study does not allow excluding the fact that DRF might improve after pyeloplasty despite a normal cortical transit.