Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

The value of oropharyngoesophageal scintigraphy in the management of aspiration into the tracheobronchial tree in neurological patients / El valor de la gammagrafía orofaringeoesofágica en el manejo de la aspiración en el árbol traqueobronquial en pacientes neurológicos

Aim. Dysphagia and bolus aspiration are two of the most frequent and invalidating symptoms of various neurological diseases. Swallowing disorders often lead to tracheobronchial aspiration with consequent pneumonia episodes. Aspiration pneumonia per se constitutes the most frequent cause of death in these patients, with mortality rate ranging from 20% to 62%. Oropharyngoesophageal scintigraphy (OPES) permits functional quantitative assessment of the different stages of swallowing, together with the detection and quantitative measurement of bolus aspiration. In this work, we analyzed the role of OPES in patients with different neurological conditions to evaluate swallowing and to detect and quantify bolus aspiration. Material and methods. We enrolled 43 neurological patients (25 women and 18 men, mean age 67.3 ± 12.4 yr) complaining of dysphagia with suspected inhalation. All patients underwent OPES with 99mTc-nanocolloid using a liquid bolus first, followed by a semi-solid bolus. We evaluated the following parameters: Oral, Pharyngeal and Esophageal Transit Time, Oro-Pharyngeal Retention Index, Esophageal Emptying Rate, and Aspiration Rate (% AR). Results. OPES detected some airway aspiration in 26/43 patients. 19 patients had tracheal aspiration (with a mean 18.1% AR) and the remaining 7 patients had bilateral broncho-pulmonary aspiration (mean 44.9% AR). Conclusions. OPES is a feasible, repeatable and noninvasive method that allows quantitative assessment of bolus aspiration into the tracheobronchial tract, thus representing a useful and accurate tool to guide the most appropriate treatment and to monitor response to therapy in neurological patients with dysphagia (AU)

Objetivo. La disfagia y la broncoaspiración de comida son 2 de los síntomas más frecuentes e invalidantes de diversas enfermedades neurológicas. Los trastornos de deglución producen una aspiración traqueobronquial y episodios de neumonía. La neumonía por aspiración constituye en sí misma la causa más frecuente de muerte en estos pacientes, con tasas de mortalidad entre 20–62%. La gammagrafía orofaringeoesofágica (OPES) permite la evaluación funcional cuantitativa de los diferentes estadios de la deglución, junto con la detección y la cuantificación de la broncoaspiración. En este trabajo analizamos el papel de la OPES para evaluar la deglución y para detectar y cuantificar la broncoaspiración de comida en pacientes con variadas situaciones neurológicas. Material y métodos. Se estudiaron 43 pacientes neurológicos (25 mujeres y 18 hombres, edad media 67,3 + 12,4 años) que presentaban disfagia y sospecha de inhalación. A todos los pacientes se les realizó OPES con 99mTc-nanocoloide usando primero un bolo líquido y después un bolo semisólido. Se evaluaron los siguientes parámetros: tiempos de tránsito oral, faríngeo y esofágico, índice de retención orofaríngea, tasa de vaciamiento esofágico, índice de retención orofaríngea, tasa de vaciamiento esofágico y tasa de aspiración (%AR). Resultados. La OPES detectó broncoaspiración en 26/43 pacientes. Diecinueve pacientes tuvieron aspiración traqueal (media AR 18,1%) y los restantes 7 pacientes aspiración broncopulmonar bilateral (media AR 44,9%). Conclusiones. La OPES es un método no invasivo, factible y repetible que permite la evaluación cuantitativa de la aspiración de comida en el tracto traqueobronquial. Por ello, representa un procedimiento útil y exacto para guiar el tratamiento más apropiado y para monitorizar la respuesta terapéutica en pacientes neurológicos con disfagia (AU)

The value of oropharyngoesophageal scintigraphy in the management of aspiration into the tracheobronchial tree in neurological patients.

AIM: Dysphagia and bolus aspiration are two of the most frequent and invalidating symptoms of various neurological diseases. Swallowing disorders often lead to tracheobronchial aspiration with consequent pneumonia episodes. Aspiration pneumonia per se constitutes the most frequent cause of death in these patients, with mortality rate ranging from 20% to 62%. Oropharyngoesophageal scintigraphy (OPES) permits functional quantitative assessment of the different stages of swallowing, together with the detection and quantitative measurement of bolus aspiration. In this work, we analyzed the role of OPES in patients with different neurological conditions to evaluate swallowing and to detect and quantify bolus aspiration. MATERIAL AND METHODS: We enrolled 43 neurological patients (25 women and 18 men, mean age 67.3±12.4 yr) complaining of dysphagia with suspected inhalation. All patients underwent OPES with (99m)Tc-nanocolloid using a liquid bolus first, followed by a semi-solid bolus. We evaluated the following parameters: Oral, Pharyngeal and Esophageal Transit Time, Oro-Pharyngeal Retention Index, Esophageal Emptying Rate, and Aspiration Rate (% AR). RESULTS: OPES detected some airway aspiration in 26/43 patients. 19 patients had tracheal aspiration (with a mean 18.1% AR) and the remaining 7 patients had bilateral broncho-pulmonary aspiration (mean 44.9% AR). CONCLUSIONS: OPES is a feasible, repeatable and noninvasive method that allows quantitative assessment of bolus aspiration into the tracheobronchial tract, thus representing a useful and accurate tool to guide the most appropriate treatment and to monitor response to therapy in neurological patients with dysphagia.

Mesolimbic dopaminergic dysfunction in Parkinson's disease depression: evidence from a 123I-FP-CIT SPECT investigation.

We investigated the striatal and extrastriatal DAT availability (SPM8) by [(123)I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without depression. A cluster with significant (p < 0.05) lower tracer binding in PD with depression was found in left cingulate cortex, persistent after correction for age, disease severity and duration, and inversely correlated with depression scores (r -0.336, p < 0.05). Our data indicate a significant association between PD depression and cingulate dopaminergic denervation supporting the dopaminergic hypothesis of PD depression.

A critical reappraisal of false negative sentinel lymph node biopsy in melanoma.

Lymphatic mapping and sentinel lymph node biopsy (SLNB) have completely changed the clinical management of cutaneous melanoma. This procedure has been accepted worldwide as a recognized method for nodal staging. SLNB is able to accurately determine nodal basin status, providing the most useful prognostic information. However, SLNB is not a perfect diagnostic test. Several large-scale studies have reported a relatively high false-negative rate (5.6-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. The main purpose of this review is to address the technical issues that nuclear physicians, surgeons, and pathologists should carefully consider to improve the accuracy of SLNB by minimizing its false-negative rate. In particular, SPECT/CT imaging has demonstrated to be able to identify a greater number of sentinel lymph nodes (SLNs) than those found by planar lymphoscintigraphy. Furthermore, a unique definition in the international guidelines is missing for the operational identification of SLNs, which may be partly responsible for this relatively high false-negative rate of SLNB. Therefore, it is recommended for the scientific community to agree on the radioactive counting rate threshold so that the surgeon can be better radioguided to detect all the lymph nodes which are most likely to harbor metastases. Another possible source of error may be linked to the examination of the harvested SLNs by conventional histopathological methods. A more careful and extensive SLN analysis (e.g. molecular analysis by RT-PCR) is able to find more positive nodes, so that the false-negative rate is reduced. Older age at diagnosis, deeper lesions, histologic ulceration, head-neck anatomical location of primary lesions are the clinical factors associated with false-negative SLNBs in melanoma patients. There is still much controversy about the clinical significance of a false-negative SLNB on the prognosis of melanoma patients. Indeed, most studies have failed to show that there is worse melanoma-specific survival for false-negative compared to true-positive SLNB patients.

Sentinel lymph node mapping in breast cancer: a critical reappraisal of the internal mammary chain issue.

Although, like the axilla, the internal mammary nodes (IMNs) are a first-echelon nodal drainage site in breast cancer, the importance of their treatment has long been debated. Seminal randomized trials have failed to demonstrate a survival benefit from surgical IMN dissection, and several retrospective studies have shown that IMNs are rarely the first site of recurrence. However, the recent widespread adoption of sentinel lymph node (SLN) biopsy has stimulated a critical reappraisal of such early results. Furthermore, the higher proportion of screening-detected cancers, improved imaging and techniques (i.e., lymphoscintigraphy for radioguided SLN biopsy) make it possible to visualize lymphatic drainage to the IMNs. The virtually systematic application of adjuvant systemic and/or loco-regional radiotherapy encourages re-examination of the significance of IMN metastases. Moreover, randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic chemotherapy, which was not routinely administered in the earlier studies. However, the contribution from IMN treatment is unclear. Lymphoscintigraphic studies have shown that a significant proportion of breast cancers have primary drainage to the IMNs, including approximately 30% of medial tumors and 15% of lateral tumors. In the few studies where IMN biopsy was performed, 20% of sentinel IMNs were metastatic. The risk of IMN involvement is higher in patients with medial tumors and positive axillary nodes. IMN metastasis has prognostic significance, as recognized by its inclusion in the American Joint Committee on Cancer staging criteria, and seems to have similar prognostic importance as axillary nodal involvement. Although routine IMN evaluation might be indicated, it has not been routinely performed, perhaps because IMN drainage with lymphoscintigraphy is more difficult to demonstrate than axillary drainage. This difference is due to technical reasons and not the absence of lymphatics to the IMN. Recent anatomical studies have confirmed a model of breast lymphatic drainage that comprises superficial, deep and perforating systems. The superficial system drains to the axilla, usually to a lymph node posterior to the pectoralis minor muscle. The deep system drains to the axilla and also anastomoses with the perforating system which drains to the IMNs. The perforating system does not connect with the superficial system. The prevalence of IMN drainage tends to reflect the method of lymphoscintigraphy, where peritumoral (deep lymphatic system) injections have a much higher likelihood of IMN drainage than subareolar or subdermal (superficial lymphatic system) injections. The fused SPECT/CT images represent a further technical solution to increase the identification of IMNs and consequently can significantly reduce the false negative rate of sentinel lymph node biopsy. Before mature results from current and future randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy and IMNs biopsy may be used to guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity.

Mild affective symptoms in de novo Parkinson's disease patients: relationship with dopaminergic dysfunction.

BACKGROUND AND PURPOSE: The investigation of the relationship between affective symptoms and dopamine transporter (DAT) density provided conflicting data in both Parkinson's disease (PD) and non-PD patients. However, the potential interference of psychoactive as well as anti-parkinsonian drugs on DAT density should be taken into account. OBJECTIVE: To investigate the relationship between affective symptoms and pre-synaptic dopaminergic function in de novo PD patients. METHODS: Forty-four de novo PD consecutive outpatients were recruited, and the severity of anxious symptoms was evaluated with the Hamilton Anxiety Rating Scale (HAM-A), the severity of depressive symptoms with the Hamilton Depression Scale (HAM-D) and the Beck Depression Inventory (BDI). Six patients had a formal diagnosis of depression. All patients performed (123) I-FP-CIT SPECT, and semi-quantitative striatal indices were calculated. RESULTS: Disease severity, as measured by Unified Parkinson's Disease Rating Scale (UPDRSIII), was inversely correlated with bilateral striatal indices. Bilateral striatal uptake was significantly positively correlated with HAM-D (r.329; r.423, respectively, right and left), BDI (r.377; r.360, respectively, right and left) and HAM-A (r.338; r.340, respectively, right and left). After controlling for age, disease duration and severity, and Mini Mental State Examination (MMSE), no significant reduction in r-values was observed (P < 0.05). CONCLUSION: Our data support the existence of a relationship between depressive and anxious symptoms and the striatal (123) I-FP-CIT uptake. The finding of an increased DAT density associated with mild affective symptoms could be due to the lack of compensatory mechanisms usually present in early PD, and/or it might have a pathogenic role in affective symptoms by reducing the dopaminergic tone in the synaptic cleft.

Personalization of radioiodine treatment for Graves' disease: a prospective, randomized study with a novel method for calculating the optimal 131I-iodide activity based on target reduction of thyroid mass.

AIM: There is no consensus regarding the most appropriate dosimetric approach to cure Graves' disease. This study describes a personalized approach based on the desired therapy-induced volume (mass) reduction in order to define the activity of 131I-iodide to be administered, based on the MIRD approach and the radiobiological Linear Quadratic Model. METHODS: A model for calculating the "optimal" final thyroid mass has been developed and published in the past years. Based on this model, it is possible to predict the thyroid absorbed dose following administration of a certain activity as a function of desired reduction of the starting mass of the gland. A total of 147 Graves' disease patients were randomly divided into four groups based on the absorbed thyroid dose, respectively 100 Gy (Group A, N.=29), 200 Gy (Group B, N.=25), and 400 Gy (Group C, N.=29), while patients of Group D (n=64) received a 131I-iodide activity calculated based on the desired "optimal" final thyroid mass. RESULTS: At one-year follow-up, 48% of patients in Group A, 64% in Group B, 97% in Group C, and 94% in Group D were cured. There was no statistical difference between cure rate in Group C versus Group D. The administered 131I-iodide activity for Group C was significantly higher than for Group D (524 ± 201 MBq versus 386 ± 173 MBq, P<0.001). CONCLUSION: These results demonstrate that the proposed method allows to optimize 131I-iodide therapy for Graves' disease patients on an individual basis, avoiding the administration of unjustified higher activities.

Radionuclide therapy and integrated protocols for bone metastases.

Bone metastases are responsible for most of the morbidity and mortality associated with solid malignant tumors, occurring in about 65-70% of the patients with advanced breast or prostate cancer. The pathophysiology of skeletal metastasis is a complex process that involves several biologic process leading to cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with the mediation of several factors including cytokines, serine proteases and tumor-derived factors. The clinical management of pain from bone metastasis, which is mostly due to indirect stimulation of sensory nerve endings by cytokines and other biologically-active compounds released locally in response to the presence of tumor cells in the bone marrow, includes several options that can be used either alone or in varying combinations, such as analgesic drugs, chemo- or hormonal therapy, bisphosponates, external beam radiation therapy, and surgery. Bone-seeking radiopharmaceuticals play an important role in the treatment of pain caused by multiple blastic or mixed-type skeletal lesions; they have in general a favorable toxicity profile and a high rate of overall clinical benefit, although they may differ in terms of duration of pain palliation and suitability for repeat treatments. The palliative effect can be attributed to the radiation targeted to the bone marrow space, and the overall average response ranges between about 45-80%, with complete response in 10-30% of the cases. In selected clinical conditions, radionuclide therapy can also constitute an effective systemic treatment beyond bone pain palliation, and a synergistic anti-tumour effect can be expected by the combination with other agents, such as chemotherapy or bisphosphonates. This review summarizes the current experience with bone-seeking radiopharmaceuticals used for bone pain palliation, focusing on indications, patients' selection, efficacy and toxicity. Finally, the available data on combination therapies showing encouraging results as to potential anti-tumor efficacy are also reviewed.

Cognitive impairment and McArdle disease: Is there a link?

McArdle disease is caused by deficiency of myophosphorylase, the muscle isoform of glycogen phosphorylase. This isoform is also expressed in astrocytes, where it seems to have a key role in neural energy metabolism. Whereas in other glycogen storage diseases cognitive impairment has been rarely reported, it has not been previously observed in McArdle disease. Here we report the case of an Italian 55-year-old woman with McArdle disease and cognitive impairment with bilateral dysfunction of prefrontal and frontal cortex (shown by neuropsychological assessment and fluorodeoxyglucose PET). Further studies are needed to assess the prevalence of central neurological manifestations in this disease.

Low frequency stimulation of the nucleus tegmenti pedunculopontini increases cortical metabolism in parkinsonian patients.

BACKGROUND AND PURPOSE: To evaluate the effects of 25-Hz deep brain stimulation of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity. METHODS: Six patients with Parkinson's disease (PD) who had bilateral stereotactic implantation of PPTg at least 12 months prior to evaluation were included in our study. All underwent, in separate sessions, 18-FDG-PET in core assessment programme for intra-cerebral transplantation as well as motor evaluation [Unified Parkinson's disease rating scale (UPDRS)--Section III] and a battery of cognitive testing. RESULTS: PPTg-ON (low bipolar contacts, 25 Hz) promoted a significant increase of glucose utilization in bilateral prefrontal areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito-frontal cortex (BA47), anterior cingulate (BA 25-32), superior frontal gyrus (BA 10) and supramarginal gyrus (BA40); a significant increase of uptake and consumption of FDG also occurred in the left ventral striatum, left subgyral (BA 46), right insula (BA 13) and right superior temporal gyrus (BA 22). PPTg-ON was associated with a significant decrease of glucose utilization in the left cerebellar anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same patients, PPTg-ON improved delayed recall (P < 0.05) and executive functions whilst the UPDRS revealed a modest (-21%) and variable treatment effect. CONCLUSIONS: Low frequency stimulation of PPTg, a sub-region of the pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar profile of cognitive improvement associated with a significant increase in FDG consumption in both prefrontal areas and mono-lateral ventral striatum. These data are consistent with multiple limbic and/or associative domains modulated by PPTg stimulation in our patients with PD.

Differences in nigro-striatal impairment in clinical variants of early Parkinson's disease: evidence from a FP-CIT SPECT study.

INTRODUCTION: In idiopathic Parkinson's disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic-rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP-CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor. OBJECTIVE: To evaluate FP-CIT uptake in TD and ART phenotypes. METHODS: We retrospectively evaluated from our database the pre-synaptic nigro-striatal function of 24 patients with TD-PD and 38 patients with ART-PD who underwent a FP-CIT SPECT within 1 year from disease onset. RESULTS: Disease duration, age at the time of SPECT scan and disease severity as measured with Unified Parkinson's Disease Rating scale part III (UPDRS III) were not statistically different between the two groups. Putamen contralateral to the most clinically affected side showed a lower FP-CIT uptake in ART patients compared to TD patients. No statistically significant differences emerged when considering bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices and caudate/putamen ratios. FP-CIT contralateral putaminal uptake correlated with the severity of rigidity and hypokinesia but not with tremor. CONCLUSIONS: These data suggest that other neurotransmitter systems apart from the nigro-striatal dopaminergic system are involved in the generation of Parkinsonian tremor, and they are consistent with previous evidence of a lack of correlation between tremor severity and FP-CIT uptake. Putaminal relative sparing in TD patients could partially explain the slower disease progression reported in this PD phenotype.

Comparison between 99mTc-sestamibi scintimammography and X-ray mammography in the characterization of clusters of microcalcifications: a prospective long-term study.

BACKGROUND: The early diagnosis of non-palpable breast cancer is the object of recent developments in the imaging procedures employed for screening purposes. In some patients, the presence of microcalcifications (MC) is the only indication of tumor. Although X-ray mammography (MRx) has high sensitivity in detecting MC, its specificity is however too low for diagnostic purposes. The aim of this study was to compare (99m)Tc-sestamibi scintimammography (SMM) and MRx in the differential diagnosis between benign and malignant clusters of MC and to assess the possible incremental value of SMM on specificity. PATIENTS AND METHODS: A total of 283 consecutive women (mean age 53+/-8 years) with MC identified on X-ray mammograms underwent SMM. Scintigraphic images were acquired 10 minutes after the i.v. injection of (99m)Tc-sestamibi (740 MBq). Planar images of both breasts were simultaneously obtained in the lateral prone position and in the anterior and oblique projections using a dual head camera. Sixty-nine women underwent surgery, whereas the remaining 214 patients had completely negative follow-up for 5 years (a 5-year follow-up period is considered the "gold standard" for diagnosing benign lesions). RESULTS: Histology demonstrated 32/69 primary breast carcinomas (prevalence of disease: 11% of all the 283 patients) and 37/69 benign lesions. The receiver operating characteristic (ROC) statistical technique was employed to compare the diagnostic value of Mrx alone to that of combined MRx and SMM. The detected difference between the areas under the MRx ROC curve (area=0.72, standard error 0.052) and the MRX and SMM ROC curve (area=0.86, standard error 0.039) was statistically significant (p<0.01). Moreover, the combination of MRx and SMM provided a significant improvement of the negative predictive value (NPV=98%) for MC with low-suspicion of malignancy at MRx. CONCLUSION: SMM can be considered as a complementary tool in the pre-operative work-up of patients with breast lesions. Furthermore, the high negative predictive value of this technique, makes it especially valuable in the perspective of reducing the number of negative breast biopsies or unnecessary surgical interventions.

Fatty acid facts, Part I. Essential fatty acids as treatment for depression, or food for mood?

The epidemic character of depressive disorders has prompted further research into dietary habits that could make an etiological contribution. One clear change in the diet of the population in developed countries has been the replacement of omega-3 polyunsaturated fatty acids by saturated fats and trans-fats as well as by omega-6 polyunsaturated fatty acids. Omega-3 and omega-6 fatty acids are essential fatty acids, and the members of the -3 and -6 series are crucial for human health. In biochemical processes there is a competition between these two series. A higher dietary intake of omega-6 results in the excessive incorporation of these molecules in the cell membrane with numerous pathological consequences, presumably due to the formation of proinflammatory eicosanoids. Members of the omega-3 family and their derivatives modulate the inflammatory action. Essential fatty acids play a major role in brain development and brain functioning. The omega-3 series members docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) provide fluidity to the cell membrane, facilitating certain processes including neurotransmission and ion channel flow. It is thought that omega-3 deficiency during the fetal and postnatal period may have a long-term effect at various levels. Epidemiological studies have demonstrated a positive association between omega-3 deficits and mood disorders. As for treatment, there is convincing evidence that add-on omega-3 fatty acids to standard antidepressant pharmacotherapy results in improved mood. There is no evidence that fatty acid monotherapy has a mood-elevating effect, with a possible exception for childhood depression. There are indications that omega-3 has a prophylactic effect on perinatal depression and has a negative effect on natural killer cell activity and T-lymphocyte function. These observations need further study in view of the popularity of self-medication.

Octreo-SPECT/CT imaging for accurate detection and localization of suspected neuroendocrine tumors.

AIM: The aim of the present study was to prospectively evaluate the add value provided by [(111)In]DTPA-octreotide single-photon emission computed tomography/computed tomography (Octreo-SPECT/CT) with respect to [(111)In]DTPA-octreotide SPECT (Octreo-SPECT) in terms of diagnostic accuracy and localization of neuroendocrine tumors (NETs). METHODS: Eighty-one consecutive patients with known or suspected NET underwent [(111)In]DTPA-octreotide scintigraphy using an integrated SPECT/low-energy-CT system (Infinia & Hawkeye; GE Medical Systems, Milwaukee, WI, USA). SPECT and fused SPECT/CT images were interpreted separately and a lesion-by-lesion analysis was performed with regard to classification (probability of NET graded on a 5-point scale) and localization of each abnormal focal tracer uptake. A subgroup analysis, distinguishing between abdominal and thoracic lesions, and a patient-by-patient analysis for likelihood of NET in each patient was also performed. Standard of reference for confirming presence or absence of NET was either histopathology or clinical/imaging follow-up data. The value of SPECT/CT imaging was assessed by ROC analysis and McNemar test. RESULTS: A final diagnosis of NET was achieved in 43 out of 81 patients and a total of 169 areas (138 NET and 31 benign/physiological) with focal tracer uptake were included in the final lesion-by-lesion analysis. SPECT/CT imaging led to a significantly higher proportion of patients (75/81=92.6% vs 64/81=79%) and lesions (163/169=96.4% vs 138/169=81.1%) correctly classified vs SPECT alone. ROC analysis confirmed that Octreo-SPECT/CT performed significantly better than Octreo-SPECT for the detection of NET on both patient- and lesion-based analysis, improving especially evaluation of abnormal tracer uptake in the abdomen. Moreover, Octreo-SPECT/CT accurately localized 160/169 (94.7%) lesions, significantly higher than SPECT alone (77/169= 45.6%). CONCLUSIONS: Octreo-SPECT/CT allows more accurate detection and localization of NETs than simple Octreo-SPECT, with major benefits for lesions located in the abdomen.

Brain perfusion effects of cholinesterase inhibitors in Parkinson's disease with dementia.

Several evidences suggest that cholinergic deficits may significantly contribute to dementia in Parkinson's disease (PDD) and acetylcholinesterase inhibitors (ChEIs) have been reported to improve cognitive symptoms in PDD, without worsening parkinsonism. Nineteen PDD patients underwent brain perfusion SPECT with (99m)Tc-ethyl cysteinate dimer after 6 months ChEIs treatment in order to evaluate the functional correlates of clinical improvement. A clear-cut cognitive improvement was reported in PDD patients with a significant improvement of ADAS-cog total score as well as of subscores exploring executive functions (p<0.01). MMSE total score did not significantly change after ChEIs but the subscore of attention significantly improved after therapy (p<0.01). No difference in motor performance as evaluated by UPDRS was reported. SPM analysis showed a significant increase of perfusion (p < 0.0001) in bilateral cingulate, and frontal regions after ChEIs. Our data confirm the efficacy of ChEIs in the treatment of dementia associated with PD mainly on attention and executive functions, and the functional findings indicate that this cognitive improvement could be associated with a sort of pharmacological frontal "re-afferentation".

Dopamine transporter imaging study in parkinsonism occurring in fragile X premutation carriers.

The authors studied four patients with parkinsonism carrying the fragile X premutation using SPECT with ([23)I]FP-CIT. They found evidence of preserved presynaptic nigrostriatal function, suggesting that parkinsonism in the X fragile premutation might be related to postsynaptic dopaminergic changes or different neurotransmitter alterations.

Paroxysmal arousal in epilepsy associated with cingulate hyperperfusion.

A patient with nocturnal frontal lobe epilepsy characterized by paroxysmal motor attacks during sleep had brief paroxysmal arousals (PAs), complex episodes of nocturnal paroxysmal dystonia, and epileptic nocturnal wandering since childhood. Ictal SPECT during an episode of PA demonstrated increased blood flow in the right anterior cingulate gyrus and cerebellar cortex with hypoperfusion in the right temporal and frontal associative cortices.

Presynaptic nigro-striatal function in a group of Alzheimer's disease patients with parkinsonism: evidence from a dopamine transporter imaging study.

The occurrence of parkinsonism in Alzheimer's disease (AD) is quite common, however the molecular and neurochemical changes underlying such extrapyramidal features in AD have been not fully understood. Post-mortem as well as in vivo imaging study have produced conflicting results as regards the existence of dopaminergic changes in AD. Aim of the present study was to investigate in vivo the nigro-striatal dopaminergic function in a group of AD patients with parkinsonism. Thirteen patients with AD and extrapyramidal features not related to past neuroleptic use (AD-P) underwent SPECT with 123I-FP-CIT, a ligand of dopamine transporter, and the data were compared with those obtained in 15 patients with Diffuse Lewy Body Dementia (DLBD), 20 patients with Parkinson's disease (PD), and 8 healthy elderly controls. The analysis of the data was performed by regions-of-interest approach and calculations of the striatal-to-non specific (occipital lobes) radioactivity ratios were made. The 123I-FP-CIT striatal uptake in patients with AD-P was similar to that obtained in the control population. Both the DLBD and PD groups showed significantly lower 123I-FP-CIT uptake in all striatal areas with respect to AD-P and control groups (p < 0.005). The lack of dopamine transporter changes in our series of AD-P patients can indicate that dopaminergic presynaptic function is preserved in this population and that different dopaminergic changes such as postsynaptic ones, or different neurotransmitter alterations might underlie the extrapyramidal features in AD.

Dopaminergic degeneration and perfusional impairment in Lewy body dementia and Alzheimer's disease.

The clinical differentiation of Lewy body dementia (LBD) from Alzheimer's disease (AD) may be difficult. The aim of the present study was to assess the dopamine transporter function and the perfusional pattern in LBD and AD in vivo. Twenty patients with probable LBD and 24 with probable AD underwent on 2 separate days a brain perfusional SPECT with 99mTc-ECD and a SPECT with (123)I-FP-CIT, a ligand of dopamine transporter. In LBD a significantly ( p<0.0005) lower ratio of specific (bilateral caudate nucleus, putamen) to non-specific (occipital cortex) (123)I-FP-CIT binding than in AD was reported. Perfusional data (SPM analysis) showed a significant ( p<0.001) decrease of temporo-parietal blood flow in AD versus LBD, whereas in LBD a significant ( p<0.001) occipital hypoperfusion with respect to AD was reported. Our findings confirm that dopaminergic nigrostriatal function is impaired in LBD. The selective occipital hypoperfusion in LBD needs to be further investigated.