Maria Teresa De Cristofaro

Brain perfusion abnormalities in drug-naive, lactate-sensitive panic patients: A SPECT study

Using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime (HM-PAO), we assessed brain perfusion in seven patients with panic disorder (PD) and in five age-matched normal subjects at rest. No patient had ever received drug treatment for panic. All patients were sensitive to lactate-induced panic. Computed tomography (CT) scans did not reveal any morphological abnormalities of the brain in any of the PD patients. Two indices of cerebral perfusion were calculated; these demonstrated alterations of brain perfusion in the PD group. Significant right-left asymmetry was found in the inferior frontal cortex of the PD patients. We also observed a significant blood flow increase in the left occipital cortex and a significant decrease in the hippocampal regions bilaterally. Although the changes seen in the inferior frontal cortex and occipital cortex may be related to anxiety experienced by the patients during the study, the pattern of hippocampal hypoperfusion appears to be characteristic of panic disorder. This suggests that the hippocampal structures may play an important role in the pathophysiology of panic disorder.

Human striatal neuroblasts develop and build a striatal-like structure into the brain of Huntington's disease patients after transplantation.

Rebuilding brain structure and neural circuitries by transplantation of fetal tissue is a strategy to repair the damaged nervous system and is currently being investigated using striatal primordium in Huntingtons disease (HD) patients. Four HD patients underwent bilateral transplantation with human fetal striatal tissues (9-12 week gestation). Small blocks of whole ganglionic eminencies were processed to obtain cell suspension and then stereotactically grafted in the caudate head and in the putamen. Follow-up period ranged between 18 and 34 months (mean, 24.7 months). Surgery was uneventful. Starting from the fourth month after grafting, neo-generation of metabolically active tissue with striatal-like MRI features was observed in 6 out of 8 grafts. The increase in D2 receptor binding suggested striatal differentiation of the neo-generated tissue in 3 patients. New tissue, connecting the developing grafts with the frontal cortex and, in one case, with the ventral striatum, was also observed. The new tissue growth halted after the ninth month post transplantation. All patients showed stabilization or improvement in some neurological indices. No clinical and imaging signs, suggestive of graft uncontrolled growth, were seen. This study provides the first evidence in humans that neuroblasts of a striatal primordium can develop and move into the brain after neurotransplantation. Primordium development resulted in the building of a new structure with the same imaging features as the corresponding mature structure, combined with short- and long-distance targeted migration of neuroblasts. The results of this study support both the reconstructive potential of fetal tissue and the remarkably retained plasticity of adult brain. Further studies are necessary to assess the clinical efficacy of the human fetal striatal transplantation.

Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease

Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinsons disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD.

Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson’s disease

PurposeThe aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson’s disease (PD) patients.MethodsTwenty-six de novo untreated PD patients were scanned with 123I-FP-CIT SPECT and 18F-FDG PET. The dopaminergic impairment was measured with putaminal 123I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BPOSEM) and the least-squares (LS) method (BPLS). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc.ResultsThe SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BPOSEM and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BPLS and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison).ConclusionsPutaminal BPLS is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.

Parkinsonism and Anderson Fabry's disease : A case report

We describe and present a videotape of a 57‐year‐old woman admitted to our Neurological Clinic at 46 years of age due to extrapyramidal manifestations suggesting Parkinsons disease (PD) and with a brain magnetic resonance imaging scan showing multi‐infarctual leukoencephalopathy. Various investigations led to the diagnosis of Anderson Fabrys disease (AFD). We discuss the possibility of correlation between the patients parkinsonism and AFD.

A direct ROI quantification method for inherent PVE correction: accuracy assessment in striatal SPECT measurements

PurposeThe clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI).MethodsAn Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP).ResultsIn the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r = 0.98, p = 0.03). ConclusionThe LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs.

Possible Pathogenetic Role of Activated Platelets in the Primary Antiphospholipid Syndrome Involving the Central Nervous System

Neurological disorders occurring in the primary antiphospholipid syndrome (neuro-PAPS) have not yet been completely understood. Platelet activation has been suggested to play a crucial role in the pathogenesis of hemostatic disorders in the antiphospholipid syndrome, but no association with neuro-PAPS has been investigated so far. Therefore, we investigated 16 patients with PAPS by flow cytometry in the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoprotein CD62. In addition, the relationship among activated platelets and anticardiolipin antibodies (aCL) was evaluated. Compared to normal subjects CD62 was found significantly increased in these patients. Furthermore, a significantly increased percentage of CD62-positive platelets was found in the neuro-PAPS group (nine patients) compared to the non-neuro-PAPS patients (seven subjects). On the contrary, no significant difference was found between the two groups with regard to aCL IgG and platelet number. Furthermore, within the neuro-PAPS group, no difference was evidenced, in the CD62-positive platelet percentage, between the four subjects with thrombocytopenia and the five with the normal blood platelet count. Similarly, neuro-PAPS subjects with previous peripheral arterial and/or venous thrombosis did not show a significantly more elevated level of CD62-positive platelets. Finally, a linear correlation was found between the aCL IgG level and the CD62-positive platelet percentage in all the patients and, more significantly, in the neuro-PAPS group, but not within the non-neuro-PAPS patients. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, aCL, and neurological disease that patients affected by PAPS might undergo.

Quantitative comparison between 99mTc-HMPAO and 99mTc-ECD: measurement of arterial input and brain retention

This report describes a comparative study between technetium-99m ethyl cysteinate dimer (ECD) and 99mTc-hexamethylpropylene amine oxime (HMPAO) in five neurological patients. The conversion kinetics of the tracers in the blood from forms capable of diffusion across the blood-brain barrier to non-diffusible forms were studied by arterial sampling and rapid octanol extraction. We observed that HMPAO has a faster conversion rate in the blood but that the fraction of the injected dose available for brain extraction is higher than in the case of ECD. Regional brain concentrations of the tracers were measured with single-photon emission tomography (SPET) 35 min and 60 min after the injection and remained stable within this interval. On the basis of the measurements of the arterial input and of SPET brain concentrations of the tracers, the regional steadystate influx constants (Ki in ml/min/g) were determined for several brain regions. In the grey matter the Ki values were (mean ± SD) 0.32 ± 0.03 and 0.35 ± 0.04 for HMPAO and ECD, respectively; in the white matter the values were 0.23 ± 0.01 and 0.23 ± 0.02, respectively. The Ki values of the two tracers in corresponding regions were closely correlated (P<0.001). The correspondence of the Ki values of ECD and HMPAO demonstrates that ECD can also be considered a tracer that may be used for quantitative measurements of brain perfusion.

Merkel cell carcinoma and iodine-131 metaiodobenzylguanidine scan

Two cases of Merkel cell carcinoma, a neuroendocrine neoplasia of the skin, investigated with iodine-131 metaiodobenzylguanidine (131i-mIBG) scintigraphy, are reported. Uptake in the tumor was evident only in 1 case. The possible diagnostic and therapeutic role of 131I-mIBG in patients with this rare neoplasm is discussed.

Clinical correlation of the binding potential with 123I-FP-CIT in de novo idiopathic Parkinson’s disease patients

PurposeThe aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane (123I-FP-CIT) binding in de novo Parkinson’s disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease.MethodsThirty-six de novo PD patients underwent 123I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal 123I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BPFBP, BPOSEM, BPLS).ResultsThe range of values of striatal BPLS was significantly greater than BPFBP and BPOSEM. For all striatal regions, estimates of BPFBP correlated well with BPOSEM (r = 0.84) and with BPLS (r = 0.64); BPOSEM correlated significantly with BPLS (r = 0.76). A good correlation was found between putaminal BPLS and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = −0.46, r = −0.42, r = −0.39, respectively). Neither putaminal BPFBP nor putaminal BPOSEM correlated with any of these motor scores.ConclusionsIn de novo PD patients, 123I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of 123I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.