Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials.

OBJECTIVE: To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers. DESIGN: One stage meta-analysis of individual patient data. DATA SOURCES: A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer. Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded. RESULTS: Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%) (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18). CONCLUSIONS: Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.

Cumulative live-birth delivery after IVF/ICSI since the progressive introduction of single-embryo transfer.

The only way to decrease the incidence of multiple pregnancies in the IVF/intracytoplasmic sperm injection (ICSI) population is to introduce single-embryo transfer (SET). This study investigated the impact of the progressive introduction of SET for the whole IVF/ICSI population from the patients' point of view by calculating the cumulative live-birth delivery rate. During a 5-year period (2001-2005), the outcome of 2164 cycles with oocyte aspiration in 1047 patients was analysed. A subanalysis was made to calculate the additional effect of frozen-thawed cycles. Survival analysis was performed with the Kaplan-Meier method and the endpoint was live-birth delivery. In this 5-year period, the cumulative live-birth delivery rate per patient was 51% after three IVF/ICSI cycles and 58% after six cycles. With a more permissive method of survival analysis, these results were 64% and 85%, respectively. The additional effect of the frozen-thawed cycles since reimbursement was only 5%. SET was progressively introduced in this period leading to a twin live-birth delivery rate of only 6.7%. It is concluded that a favourable outcome was observed for the cumulative live-birth delivery rate since the introduction of SET but with a disappointing additional effect of the frozen-thawed cycles.

The obstetrical and neonatal outcome of babies born after single-embryo transfer in IVF/ICSI compares favourably to spontaneously conceived babies.

BACKGROUND: Recently, concern has risen about poor obstetrical and neonatal outcome of singletons after IVF/ICSI. Because the population of patients receiving single-embryo transfer (SET) resulting in singleton pregnancies is different from the one that would have become pregnant (with a singleton) before SET was introduced, we wanted to investigate whether the outcome of singleton pregnancies after SET differed from spontaneously conceived singletons. METHODS: The obstetrical and early neonatal outcome of all pregnancies originating from SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003, was prospectively collected and analyzed. RESULTS: Data from 251 singleton pregnancies and births after SET were analyzed and compared to data from 59,535 spontaneously conceived singletons retrieved from the Centre for Perinatal Epidemiology. The mean birthweight of the singletons after SET was 3322 g (+/-538 SD) versus 3330 g (+/-531 SD) for the spontaneously conceived singletons (P = 0.82). The mean gestational age was 38.7 weeks (+/-1.9 SD) for SET and 38.9 weeks (+/-1.8 SD) for spontaneously conceived singletons (P = 0.06). The proportion of very preterm birth (<32 weeks) was 0.8% in each group, and the proportion of preterm birth (<37 weeks) was 10.0% for SET singletons and 6.24% for spontaneous singletons (P = 0.03). However, mean birthweight of very preterm, preterm and term SET singleton babies was similar to the mean birthweight in every category of gestational age in the spontaneous conceived control group. Stillbirth was 0.4% for both populations (P = 0.99). CONCLUSIONS: Good prognosis patients, in whom SET is applied, do not only have a higher chance of conception but do not have an unfavourable outcome of their singleton baby when compared to spontaneous singletons.

Single top quality embryo transfer as a model for prediction of early pregnancy outcome.

BACKGROUND: Single embryo transfer (particularly of a top quality embryo) is an excellent model to correlate embryo quality in terms of morphological criteria to early pregnancy. We investigated whether this model could provide us with more information on what happens after implantation in the first trimester of pregnancy. METHODS: The outcome of 370 consecutive single top quality embryo transfers in patients younger than 38 years was analysed for pregnancy and first-trimester pregnancy loss (FTPL) before 13 weeks of gestation. Analysis was done on each cohort of embryos from which the transferred top quality embryo was selected. Serum HCG levels were measured on day 8 and day 12 after day 3 embryo transfer. The HCG index was calculated as the level of HCG on day 12/HCG on day 8. RESULTS: The pregnancy rate after single top quality embryo transfer was 51.9%. This was independent of the patients' age. FTPL, however, appeared to be age dependent: 15.4% for the whole group, 9% in patients younger than 30 years and 19% in patients above 30 years. The pregnancy rate was 50% in IVF cycles and 52% in ICSI cycles; FTPL was 19% in IVF cycles and 10% in ICSI cycles. Multiple regression analysis showed that these differences originated from age differences between both populations rather than from technique-related factors. An HCG level >or=45 IU/l on day 12 was predictive for ongoing pregnancy with 75.6% sensitivity and 100% specificity; an HCG index >or=3.5 similarly predicted ongoing pregnancy with 72.3% sensitivity and 100% specificity. CONCLUSIONS: These data show that embryo selection for transfer on day 3 can be used as an excellent tool for prediction of pregnancy but not for prediction of FTPL. The pregnancy rate of a single top quality embryo is not related to age, whereas FTPL is age dependent.

A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles.

BACKGROUND: We analysed the difference in maternal, neonatal and total costs after single (SET) versus double day 3 embryo transfer (DET). METHODS: We performed a two-centre prospective study of women in their first IVF/ICSI cycle choosing between SET or DET. Infertility treatment data were gathered from a database; maternal and neonatal outcome data from a case report form (CRF); health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills. SET was performed in 206/367 (56.1%) and DET in 161/367 (43.9%) women. RESULTS: In all, 367 transfers yielded 186 positive pregnancy tests, 148 ongoing pregnancies and 136 live deliveries (50.7, 40.3 and 37.1% per embryo transfer) of which 15 (11.0%) were twins. Live birth rate was 37.4% for SET, 36.6% for DET. Intention-to-treat analysis showed differences for: duration of pregnancy (SET: 39.0 +/- 1.4 versus DET: 38.3 +/- 2.2 weeks; P = 0.055), percentage prematurity (8.5 versus 23.8%; P = 0.033), percentage of neonates hospitalized (5.7 versus 17.9%; P = 0.121) and duration of neonatal hospitalization (6.3 +/- 2.2 versus 10.3 +/- 10.1 days; P = 0.01). Total cost after DET was higher (SET: 4700 +/- 3239 versus DET: 8613 +/- 10 105; P = 0.105), due to significantly higher neonatal costs (451 +/- 957 versus 3453 +/- 8154; P < 0.001) and not to differences in maternal costs (4250 +/- 2882 versus 5160 +/- 4106; P = 0.152). CONCLUSIONS: This prospective health economic study shows that transfer of a single top quality embryo is equally effective as, but substantially cheaper than, double embryo transfer in women <38 years of age in their first IVF/ICSI cycle.

Cryopreservation as a tool to reduce multiple birth.

The potential role of embryo cryopreservation from the point of view of prevention of multiple pregnancies is analysed. Cryopreservation is an unavoidable option in stimulated IVF/intracytoplasmic sperm injection (ICSI), but at the same time an underestimated tool in the prevention of twins. There is a need for an evaluation system not only of the cryotechnology process per se, but also of the true augmenting effect of cryopreservation on the total reproductive potential of a single oocyte harvest. Only cryopregnancies occurring after an unsuccessful fresh cycle (possibly followed by one or more unsuccessful freeze-thaw cycles with embryos from the same harvest) truly reflect the augmentation potential of cryopreservation. This potential is greater than generally thought. First, the efficacy of cryopreservation is suboptimal with survival rates between 30 and 70%. Second, if single-embryo transfer were applied in a much larger proportion of cycles than is presently the case, more embryos would be available for cryopreservation, resulting in more and more successful freeze-thaw cycles. In the future, the combination of elective single-embryo transfer with an optimized cryopreservation programme is likely to become the standard of care for routine IVF/ICSI treatment.

[(123)I]beta-CIT SPECT is a useful method for monitoring dopaminergic degeneration in early stage Parkinson's disease.

OBJECTIVES: To examine the validity of [(123)I]beta-CIT SPECT for monitoring the progression of dopaminergic degeneration in Parkinson's disease; to investigate the influence of short term treatment with D(2)receptor agonists on striatal [(123)I]beta-CIT binding; and to determine the sample size and frequency of SPECT imaging required to demonstrate a significant effect of a putative neuroprotective agent. METHODS: A group of 50 early stage Parkinson's disease patients was examined. Two SPECT imaging series were obtained, 12 months apart. The mean annual change in the ratio of specific to non-specific [(123)I]beta-CIT binding to the striatum, putamen, and caudate nucleus was used as the outcome measure. RESULTS: A decrease in [(123)I]beta-CIT binding ratios between the two images was found in all regions of interest. The average decrease in [(123)I]beta-CIT binding ratios was about 8% in the whole striatum, 8% in the putaminal region, and 4% in the caudate region. Comparison of scans done in nine patients under two different conditions-in the off state and while on drug treatment-showed no significant alterations in the expression of striatal dopamine transporters as measured using [(123)I]beta-CIT SPECT. Power analysis indicated that to detect a significant (p < 0.05) effect of a neuroprotective agent with 0.80 power and 30% of predicted protection within two years, 216 patients are required in each group when the effects are measured in the whole putamen. CONCLUSIONS: [(123)I]beta-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in Parkinson's disease and may provide an objective method of measuring the effectiveness of neuroprotective treatments. Short term treatment with a D(2)agonist does not have a significant influence on [(123)I]beta-CIT binding to dopamine transporters. If the latter finding is replicated in larger groups of patients, it supports the suitability of [(123)I]beta-CIT SPECT for examining the progression of neurodegeneration in patients being treated with D(2)receptor agonists.

Impact of patients' choice for single embryo transfer of a top quality embryo versus double embryo transfer in the first IVF/ICSI cycle.

BACKGROUND: The aim of this study was to evaluate the impact of transferring a single top quality embryo in the first IVF/ICSI cycle of patients <38 years old who chose to have one or two embryos transferred. METHODS: A total of 262 patients participated in the study, and 243 transfers were performed: 156 (64%) patients chose the transfer of a single top quality embryo, if available, and two non-top quality embryos if not available; 87 (36%) patients chose to have a double embryo transfer regardless of embryo quality. RESULTS: In the first group an ongoing pregnancy rate of 40% (63/156) with a twin pregnancy rate of 2% (1/63) was achieved. In the second group the ongoing pregnancy rate was 44% (38/87) with 26% (10/38) twin pregnancies. In the patient group with only one embryo transferred, irrespective of the patient's choice, the ongoing pregnancy rate was 43% (54/127) with no twin pregnancies. For the study population as a whole, the ongoing pregnancy rate was 42% (101/243) with 11% (11/101) twins. CONCLUSION: We conclude that the introduction of single embryo transfer in the first IVF/ICSI cycle is highly acceptable in women <38 years old.

[Prevention of twin pregnancy after IVF/ICSI using embryo transfer]. / Preventie van tweelingzwangerschap na IVF/ICSI door transfer van een embryo.

One of the negative aspects of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) is the increased risk of multiple pregnancies. Multiples of high order (triplets and pregnancies of higher order) are obsolete to both doctors and patients and need to be avoided. However, there is an epidemic of twin pregnancies with a higher risk of obstetric, perinatal and neonatal complications than singleton pregnancies and with an important psychosocial, economic and financial impact for the parents to be. A reduction in the number of twins can only be obtained by transfer of one embryo. If this guideline would be applied to all cycles, a dramatic fall in pregnancy rate would occur. In a selected patient group one selected embryo with an excellent implantation potential can be transferred.

Rigidity decreases resting tremor intensity in Parkinson's disease: A [(123)I]beta-CIT SPECT study in early, nonmedicated patients.

Tremor is one of the clinical hallmarks of Parkinson's disease (PD). Although it is accepted that other classic symptoms of PD such as rigidity and bradykinesia result from a degeneration of the nigrostriatal system and subsequent reduction in striatal dopamine, the pathophysiology of resting tremor remains unclear. The majority of recent single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies, using various radioligands, demonstrated significant correlation between striatal radioligand bindings and the degree of parkinsonian symptoms such as rigidity and bradykinesia, but not tremor. We investigate the relationship between the degeneration of the nigrostriatal pathway and the appearance of resting tremor, taking into account the possible interference of rigidity with the resting tremor. Thirty early and drug-naïve PD patients were examined. Tremor and rigidity of the arms were assessed using UPDRS, and the power of tremor was estimated using spectral analysis of tremor peaks. [(123)I]beta-CIT SPECT was used to assess degeneration of the dopaminergic system in PD patients. A comparison between asymmetry indices showed that in terms of both tremor and rigidity, the most affected arm corresponded significantly with the contralateral striatum, having the largest reduction in radioligand binding. Furthermore, tremor power accounted for a significant part of variance in the contralateral striatum, suggesting a relationship between this PD symptom and the degeneration of the dopaminergic system. Further, the degree of tremor was reduced with increasing rigidity. However, correcting for the influence of rigidity, the significant contribution of tremor in the variance in the contralateral striatal [(123)I]beta-CIT binding disappeared. When the confounding influence of rigidity is taken into account, no significant direct relationship between dopaminergic degeneration and the degree of tremor could be found. Other pathophysiological mechanisms should be similarly investigated in order to further our understanding of the origin of resting tremor in PD.

[123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease.

We investigated the applicability [123I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43-73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [123I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [123I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [123I]FP-CIT binding ratios in whole striatum. Our findings indicate that [123I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies.

Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. A[123I]-IDEX SPECT study.

RATIONALE: In vitro data have shown anticholinergic properties of the atypical antipsychotic drug olanzapine. Substantial occupancy of muscarinic receptors may be an explanation for the low incidence of extrapyramidal side effects induced by olanzapine. OBJECTIVES: To obtain an in vivo measurement of muscarinic receptor occupancy by olanzapine compared with risperidone in patients with schizophrenia stabilised on medication. METHODS: Five patients with schizophrenia treated with olanzapine and five patients treated with risperidone were studied. Muscarinic receptor occupancy in the striatum and cortex was studied in vivo with SPECT using [123I]-IDEX as a radioligand. SPECT data were compared with those of six healthy subjects. RESULTS: Patients stabilised on olanzapine showed significantly lower mean (+/-SD) striatal and cortical (1.50+/-0.21 and 1.51+/-0.22, respectively) muscarinic receptor binding ratios of [123I]-IDEX (reflecting higher levels of muscarinic receptor occupancy) than controls (3.91+/-0.61 and 3.65+/-0.70, respectively). Furthermore, [123I]-IDEX binding ratios in patients treated with risperidone were slightly lower than controls, reaching significance only in the striatum (2.99+/-0.27 versus 3.91+/-0.61, for risperidone and controls). CONCLUSIONS: The substantial occupancy of muscarinic receptors in the striatum and cortex by olanzapine may be an explanation for the low incidence and severity of extrapyramidal side effects of this antipsychotic drug. Furthermore, it may also explain the anticholinergic side effects of olanzapine.

Dopamine transporter density in patients with tardive dyskinesia: a single photon emission computed tomography study.

RATIONALE: Tardive dyskinesia occurs frequently in schizophrenic patients chronically treated with classical antipsychotic medication. It may be caused by loss of dopaminergic cells, due to free radicals as a product of high synaptic dopamine levels. OBJECTIVE: To evaluate dopamine transporter density in the striatum in patients with tardive dyskinesia. METHODS: Striatal [123I]FP-CIT binding was measured with SPECT in seven schizophrenic patients with tardive dyskinesia and eight healthy controls. RESULTS: No significant difference was found between striatal [123I]FP-CIT binding ratios in patients with tardive dyskinesia and controls. CONCLUSIONS: This preliminary study indicates no change in striatal dopamine transporter density in schizophrenic patients with tardive dyskinesia. This finding does not support the hypothesis that tardive dyskinesia is caused by dopaminergic cell loss.

Quantitative analysis of 99Tcm-sestamibi myocardial perfusion SPECT using a three-dimensional reference heart: a comparison with experienced observers.

BACKGROUND: Quantification of myocardial perfusion single photon emission computed tomography (SPECT) may improve scintigraphic analysis. Recently, a fully operator independent technique for the quantification of myocardial perfusion SPECT was described, based on a normal three-dimensional averaged reference heart. The purpose of this study was to compare the automated SPECT quantification technique with experienced observers. METHODS: A total of 43 patients, 36 with one-vessel coronary artery disease (CAD) and seven with a low likelihood of CAD, underwent 99Tcm-sestamibi SPECT (99Tcm-MIBI SPECT). Three experienced observers and a panel (composed of the three observers), blinded to the clinical and angiographic data, analysed the size and severity of perfusion defects and the relation to the distribution areas of the coronary arteries. Inter-observer agreement was calculated by using kappa (kappa) statistics. RESULTS: The inter-observer agreement between the human observers and the automated quantitative analysis, for severity and size of perfusion abnormality, was moderate (kappa range 0.38-0.68), while this was fair between three individual observers (kappa range 0.36-0.87) and good between the individual observers and the panel (kappa range 0.63-0.89). There were no differences between the quantitative analysis and the panel in the allocation of perfusion abnormalities to the affected coronary artery. CONCLUSIONS: The operator independent quantification method showed a moderate agreement with individual observers and a panel analysis for size and severity of perfusion abnormalities. The automatic quantification has a similar ability to assign perfusion abnormalities to the diseased coronary artery as compared to an expert panel.

Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT.

Disturbances in the dopamine (DA) system are thought to play a major role in schizophrenia. Amphetamine-induced release of endogenous DA is shown to be enhanced in schizophrenia, as is striatal [18F]FDOPA uptake in the striatum. It is not clear if the density of DA neurons is altered in schizophrenia. By studying the DA transporter with [123I]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied. Using [123I]FP-CIT SPECT, DA transporter density in the striatum was studied in 36 young patients with schizophrenia. Ten patients were antipsychotic (AP)-naive, 15 were treated with olanzapine, eight with risperidone and three were AP-free. A control group of 10 age-matched volunteers was included. Striatal [123I]FP-CIT binding was not significantly different between AP-naive patients (2.87), patients treated with olanzapine (2.76), patients treated with risperidone (2.76), AP-free patients (2.68) and controls (2.82) (F=0.07,p=0.98). Unexpectedly, striatal [123I]FP-CIT binding in females was significantly higher than in males (3.29 and 2.70, respectively; t=-2.56, p=0.014).Concluding, functional changes in the dopaminergic system in schizophrenia are not likely to be reflected in a change in DA transporter density. Moreover, DA transporter density does not seem to be altered by AP medication.

Avoiding multiple pregnancies in ART: a plea for single embryo transfer.

It has been generally accepted that triplets after IVF/intracytoplasmic sperm injection (ICSI) can and should be avoided by adopting a standard strategy of replacing no more than two embryos. However, there is an increasing awareness of the risks and costs and of the epidemic size of twin pregnancies after IVF/ICSI. This has resulted in efforts to replace no more than one embryo. However, this approach has been hampered by our relative inability to identify embryos with a very high implantation potential. To identify such embryos, a number of strategies are being considered, both at the two pronuclear (2PN), early cleavage and the blastocyst stages. At the 2PN stage, the polarity characteristics of the nucleoli have been shown to be correlated with a high implantation rate. Similarly, the morphological characteristics at day 2 and 3 have been used to describe top quality embryos in approximately 75% of all IVF/ICSI cycles. Blastocyst culture has resulted in very high implantation rates in the hands of some authors. No approach has shown its superiority at present, but initial experience with single embryo transfer (SET) at the early cleavage stage by Scandinavian and Belgian groups shows that an ongoing pregnancy rate of 35% and more can be achieved. Proper identification of patients at risk of a twin pregnancy after double embryo transfer is equally important. It is clear that mainly young patients (aged <34 years) during their first, perhaps first two, IVF/ICSI cycles constitute the main population at risk (responsible for >80% of all twins) and are the main target group for twin prevention by SET of a top quality embryo at whatever stage. Therefore, in our opinion, although a further fine-tuning of both embryo and patient characteristics relating to a high risk for (twin) pregnancy is desirable, SET should be introduced carefully and progressively in each IVF/ICSI programme from now on. Correct counselling is very important and both public and private insurers will have to join in the discussion.

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers.

Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [123I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of +/-110 MBq [123I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [123I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [123I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [123I]FP-CIT binding ratios than males. This effect of gender on [123I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies.

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

OBJECTIVE: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

The development of hemispheric asymmetry in human motion VEPs.

In six healthy adults we examined the sources underlying P1 and N2 of the motion VEP. For this purpose was acquired, in addition to the VEP, MRI images and patterns of regional cerebral blood flow with SPECT for three of the subjects. With the same motion stimulus we also examined the spatial distribution of N2 in children. In both adults and children left and right half-field responses were compared. It was found that N2 is generated by extrastriate activity and that motion stimuli are not equivalently processed in the two cerebral hemispheres. In adults, N2 dominates in one hemisphere irrespective of the visual half-field used for stimulation whereas children show an ipsilateral maximum for N2 upon half-field presentation.