Fabrizio Cocciolillo

MIBG scintigraphy in differential diagnosis of Parkinsonism: a meta-analysis

ObjectiveDifferential diagnosis between Parkinson’s disease (PD) and other Parkinsonism using clinical criteria or imaging methods is often difficult. The purpose of this study is to systematically review and meta-analyze published data about the diagnostic performance of myocardial innervation imaging using 123I-metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between PD and other Parkinsonism.MethodsA comprehensive computer literature search of studies published through March 2011 regarding MIBG scintigraphy in patients with PD and other Parkinsonism was performed in PubMed/MEDLINE and Embase databases. Only studies in which MIBG scintigraphy was performed for differential diagnosis between PD and other Parkinsonism were selected. Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis between PD and other Parkinsonism.ResultsNineteen studies comprising 1,972 patients (1,076 patients with PD, 117 patients with other Lewy body diseases and 779 patients with other diseases) were included in this meta-analysis. The pooled sensitivity of MIBG scintigraphy in detecting PD was 88% (95% CI 86–90%); the pooled specificity of MIBG scintigraphy in discriminating between PD and other Parkinsonism was 85% (95% CI 81–88%). The area under the ROC curve was 0.93.ConclusionsIn patients with clinically suspected PD, myocardial innervation imaging demonstrated high sensitivity and specificity. MIBG scintigraphy is an accurate test in this setting. Nevertheless, possible causes of false-negative and false-positive results should be kept in mind when interpreting the scintigraphic results.

Diagnostic performance of 18 F-dihydroxyphenylalanine positron emission tomography in patients with paraganglioma: a meta-analysis

PurposeThe aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of 18F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG).MethodsA comprehensive computer literature search of studies published through 30 June 2011 regarding 18F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of 18F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 18F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed.ResultsEleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of 18F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87–94%] on a per patient-based analysis and 79% (95% CI 76–81%) on a per lesion-based analysis. The pooled specificity of 18F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86–99%) on a per patient-based analysis and 95% (95% CI 84–99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of 18F-DOPA PET or PET/CT was found. A significant increase in sensitivity of 18F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed.ConclusionIn patients with suspected PG 18F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. 18F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind. Furthermore, SDHB gene mutations could influence 18F-DOPA PET or PET/CT diagnostic performance.

Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson's disease and multiple-system atrophy: A systematic review and a meta-analysis

BACKGROUND AND PURPOSE This study was designed to review the diagnostic performance of iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between Parkinsons disease (PD) and multiple-system atrophy (MSA). METHODS A comprehensive computer literature search of studies published through March 2011 regarding MIBG scintigraphy in patients with PD and MSA was performed in PubMed/MEDLINE and Embase databases. Only studies in which MIBG scintigraphy was performed for differential diagnosis between PD and MSA were selected. Pooled sensitivity and specificity of MIBG scintigraphy were presented with a 95% confidence interval (CI). The area under the ROC curve was calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis between PD and MSA. RESULTS Ultimately, we identified 12 studies comprising a total of 1226 patients (593 patients with PD, 117 patients with other Lewy body disease, 129 patients with MSA, and 387 patients with other diseases). The pooled sensitivity of MIBG scintigraphy to detect PD was 89% (95% CI: 86-91%); the pooled specificity of MIBG scintigraphy to discriminate between PD and MSA was 77% (95% CI: 68-84%). The area under the ROC curve was 0.93. CONCLUSIONS MIBG scintigraphy is an accurate test for PD detection and differential diagnosis between PD and MSA; this method shows high sensitivity and adequate specificity in this field. Nevertheless, possible causes of false negative and false positive findings should be considered when interpreting the scintigraphic results.

Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I-FP-CIT SPECT study.

PurposePsychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of 123I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson’s disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity.MethodsEnrolled in the study were 21 patients with Parkinson’s disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific 123I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects.ResultsAs expected, DAT availability was significantly decreased in patients with Parkinson’s disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson’s disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = −0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = −0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = −0.71, p = 0.004, and r = −0.75, p = 0.002, respectively). There were no correlations between psychometric scores and 123I-FP-CIT uptake ratios in healthy subjects.ConclusionWe found association between presynaptic dopaminergic function and affective symptoms in different movement disorders. Interestingly, the inverse correlation was present in each group of patients, supporting the fascinating perspective that common subcortical substrates may be involved in both anxiety and depression dimensions and movement disorders.

Detection Rate of Recurrent Medullary Thyroid Carcinoma Using Fluorine-18 Dihydroxyphenylalanine Positron Emission Tomography: A Meta-analysis

RATIONALE AND OBJECTIVES The aim of this study was to perform a meta-analysis of published data about the diagnostic performance of (18)F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) or PET/computed tomography (CT) in detecting recurrent medullary thyroid carcinoma (MTC). MATERIALS AND METHODS A comprehensive literature search of studies indexed in the PubMed/MEDLINE, Scopus, and Embase databases through January 2012 and regarding (18)F-DOPA PET or PET/CT in patients with suspected recurrent MTC was carried out. Pooled detection rates (DR) in per patient and per lesion analyses were calculated. A subanalysis considering serum levels of calcitonin and carcinoembryonic antigen, device used, and carbidopa pretreatment was also performed. RESULTS Eight studies including 146 patients with suspected recurrent MTC were included. The DRs of (18)F-DOPA PET and PET/CT in per patient and per lesion analyses were 66% and 71%, respectively. DRs significantly increased in patients with serum calcitonin ≥1000 ng/L (86%) and calcitonin doubling times <24 months (86%). CONCLUSIONS Fluorine-18-DOPA PET and PET/CT may be useful functional imaging methods in detecting recurrent MTC. The DR of recurrent MTC using these imaging methods increases in patients with higher calcitonin levels and lower calcitonin doubling times.

18 F-FDG PET-CT during chemo-radiotherapy in patients with non-small cell lung cancer: the early metabolic response correlates with the delivered radiation dose

BackgroundTo evaluate the metabolic changes on 18 F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (18 F-FDG PET-CT) performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiation dose and with the clinical outcome.MethodsTwenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent 18 F-FDG PET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PET-CT) of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PET-CT). The parameters evaluated were: the maximum standardized uptake value (SUVmax) of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV).ResultsSUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks from the end of treatment (p<0.0000, p<0.0002, respectively). SUVmax of lymph nodes showed a trend towards a reduction during chemo-radiotherapy (p=0.06) and decreased significantly (p=0.0006) at the end of treatment. There was a significant correlation (r=0.53, p=0.001) between SUVmax of the tumor measured at during-RT PET-CT and the total dose of radiotherapy reached at the moment of the scan. Disease progression free survival was significantly (p=0.01) longer in patients with complete metabolic response measured at post-RT PET-CT.ConclusionsIn patients with locally advanced NSCLC, 18 F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET.

The Contursi Family 20 Years Later: Intrafamilial Phenotypic Variability of the SNCA p.A53T Mutation

The SNCA/alpha-synuclein p.A53T mutation segregating in the Contursi kindred was the first mutation ever described in inherited Parkinson’s disease (PD). We directly examined 10 subjects (4 PD patients and 6 asymptomatic relatives) of a branch of the Contursi kindred. We also collected data on 11 members affected by history, through interviews and inspection of available medical records. Nine had died in the fourth to seventh decade diagnosed with PD (plus psychiatric features in 3), whereas 2 were reported to have severe psychiatric disturbances and were unavailable for examination. After obtaining ethics approval and written informed consent, all subjects underwent a complete neurological examination (see Video 1) and SNCA p.A53T mutation testing. The 4 PD patients (age, 42 6 9.8 years), and 2 unaffected individuals (age, 29.5 6 2.1 years) resulted as heterozygous for the mutation. Two affected (III:1, IV:1) and 2 unaffected (IV:2, IV:6) carriers also underwent extensive neuropsychological and psychiatric assessment, olfaction evaluation, and dopamine transporter imaging with single-photon emission computed tomography (DAT-SPECT); 3T brain MRI was performed in 3 subjects (III:1, IV:2, and IV:6; Fig. 1). Although the overall phenotype in the 4 patients was typical of SNCA-related PD with early, asymmetric onset, initial good response to dopaminergic therapy and early motor complications, a relevant variability was observed in the combination and severity of motor symptoms (partially responding to levodopa and DBS in III-9) and nonmotor features (Table 1). Age at onset varied from 26 to 48 years (mean, 32.7 6 10.5), with longer disease duration than previously reported (from 2 to 19 years; mean, 9.26 8.5). Cognitive deficits were present in all 4 patients, ranging from frank dementia in those with longer disease duration (III-8, III-9) to moderate cognitive impairment (III-1) or slight isolated executive dysfunction (IV-1) in those with a shorter one. Depression and anxiety were detected in 3 patients, behavioral disorders in 2, and dysautonomia in 2. Olfaction was impaired in both tested patients. Although the variable severity could depend on the different disease duration, the wide range of ages at onset among carriers of the same genetic mutation remains unexplained, suggesting the existence of yet unknown environmental, genetic, and/or epigenetic modifiers. Interestingly, 2 asymptomatic carriers, ages 31 and 28 years, were clinically unaffected. Their general cognitive functions were normal and they did not refer any sleep or mood disorder. However, the younger one (IV:2) presented an objective olfactory deficit and an abnormal DAT scan, suggesting an underlying, still subclinical, neurodegenerative process. The existence of SNCA mutation carriers who remain clinically asymptomatic at ages beyond the expected age of onset has been reported, implying reduced penetrance. However, our carriers were still younger than the latest age of onset in the family; therefore, any conclusion would be merely speculative and further clinical follow-up is necessary. In conclusion, our data further highlight the relevant intrafamilial phenotypic variability in carriers of the SNCA p.A53T mutation, suggesting a role for yet unknown genetic or environmental modifiers. Follow-up studies are encouraged to better define the clinical spectrum of PD caused by SNCA gene mutations.

Deep Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex in Alcohol Use Disorder Patients: Effects on Dopamine Transporter Availability and Alcohol Intake

Repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex may affect neuro-adaptations associated with alcohol use disorder (AUD), potentially influencing craving and alcohol intake. We investigated alcohol intake and dopamine transporter (DAT) availability by Single Photon Emission Computed Tomography (SPECT) in the striatum of AUD patients before and after deep rTMS. Fourteen patients underwent baseline clinical and SPECT assessment. Eleven out of fourteen patients were randomized into two groups for the REAL (n.5) or SHAM (n.6) treatment. Clinical and SPECT evaluations were then carried out after four weeks of rTMS sessions (T1). At baseline, AUD patients showed higher striatal DAT availability than healthy control subjects (HC). Patients receiving the REAL stimulation revealed a reduction in DAT availability at T1, whereas the SHAM-treated group did not. In addition, patients receiving the REAL stimulation had a decrease in alcohol intake. The results of this longitudinal pilot study may suggest a modulatory effect of deep rTMS on dopaminergic terminals and a potential clinical efficacy in reducing alcohol intake in AUD patients. Further investigations are required to confirm these preliminary data.

The role of PET/CT in the evaluation of patients affected by limbic encephalitis: A systematic review of the literature☆

Autoimmune limbic encephalitis (LE) is a rare disorder affecting the medial temporal lobe of the brain. Although brain Magnetic Resonance (MR) has been widely evaluated and is currently considered essential in the suspicion of LE, Positron Emission Tomography/Computed Tomography (PET/CT) has been demonstrated to be useful also in the evaluation of brain inflammatory diseases such as encephalitis. We therefore aim to review the current literature about the role of PET/CT in the evaluation of patients affected by LE.

Atypical presentation of plasma cell leukemia secondary to multiple myeloma detected by F-18 FDG PET/CT

We report a case of atypical muscle localization of plasma cell leukemia (PCL), arisen from a secondary leukemic transformation of multiple myeloma (MM), detected by F-18 FDG PET/CT. A 57-year-old woman with a history of MM received chemotherapy and hematopoietic stem cell transplantation with complete treatment response. Five years later, the patient presented a recurrence of MM and an evolution in PCL. F-18 FDG PET/CT showed areas of increased radiopharmaceutical uptake in some muscles of the right leg and right thigh, corresponding to muscle localization of PCL, therefore allowing adequate treatment planning.