Retraction Note: Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome.

The article "Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome", by K. Dhuli, M.C. Medori, C. Micheletti, K. Donato, F. Fioretti, A. Calzoni, A. Praderio, M.G. De Angelis, G. Arabia, S. Cristoni, S. Nodari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 13-19-DOI: 10.26355/eurrev_202312_34685-PMID: 38112944 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Unclear methodology and patient recruitment -       Discrepancies among data reported in the text and tables -       Unreliable results -       Undeclared conflict of interest Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the article. The authors disagree with this retraction. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34685.

Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome.

OBJECTIVE: COVID-19 patients experience, in 10-20% of the cases, a prolonged long-COVID syndrome, defined as the persistence of symptoms for at least two months after the infection. The underlying biological mechanisms of this syndrome remain poorly understood. Several hypotheses have been proposed, among which are the potential autoimmunity resulting from molecular mimicry between viral spike protein and human proteins, the reservoir and viral reproduction hypothesis, and the viral integration hypothesis. Although official data state that vaccinal spike protein is harmless and remains at the site of infection, several studies proposed spike protein toxicity and found it in blood circulation several months after the vaccination. To search for the presence of viral and vaccine spike protein in a cohort of long-COVID patients. PATIENTS AND METHODS: In this study, we employed a proteomic-based approach utilizing mass spectrometry to analyze the serum of 81 patients with long-COVID syndrome. Moreover, viral integration in patients' leukocytes was assessed with a preliminary study, without further investigation. RESULTS: We identified the presence of the viral spike protein in one patient after infection clearance and negativity of COVID-19 test and the vaccine spike protein in two patients two months after the vaccination. CONCLUSIONS: This study, in agreement with other published investigations, demonstrates that both natural and vaccine spike protein may still be present in long-COVID patients, thus supporting the existence of a possible mechanism that causes the persistence of spike protein in the human body for much longer than predicted by early studies. According to these results, all patients with long-COVID syndrome should be analyzed for the presence of vaccinal and viral spike protein.

Serum proteomic profiling reveals potential inflammatory biomarkers in long-COVID patients: a comparative analysis with healthy controls.

OBJECTIVE: The highly transmissible severe acute respiratory syndrome-Coronavirus-2 was responsible for the 2020 COVID-19 pandemic. COVID-19 mostly affects the respiratory system; however, this infection also affects several other organs. In addition, the sequelae of this disease affect patients for several months after recovery, resulting in long-COVID syndrome. PATIENTS AND METHODS: In order to characterize the differences between healthy control individuals and long-COVID patients, proteomic profiling of the serum of both groups was performed by mass spectrometry. The obtained data were analyzed with multivariate and univariate statistical analyses. RESULTS: Initially, performing a partial latent square discriminant analysis (PLS-DA) made it possible to identify thirty-three proteins of interest, which were then subjected to a receiver operating characteristic (ROC) analysis. Four proteins were identified as potential stand-alone biomarkers: Sirtuin 1, Natriuretic Peptide B, Hemopexin, and Arachidonate 5-Lipoxygenase. Moreover, a multivariate ROC analysis identified a panel of biomarkers composed of Natriuretic Peptide B, Anterior Gradient 2 Protein, Adiponectin, Endothelin Converting Enzyme 1, Interferon Induced Transmembrane Protein 1, Mannose Binding Lectin 2, Prostaglandin-Endoperoxide Synthase 2, Pirin, Prostaglandin Reductase 1 and Cystatin C. CONCLUSIONS: The identified biomarkers are associated with inflammatory processes, corroborating literature evidence that long-COVID patients develop an inflammatory state that damages many tissues. Nevertheless, these data should be validated in a larger cohort.

Linking pathogenic and likely pathogenic gene variants to long-COVID symptoms.

OBJECTIVE: Long-COVID is a clinical syndrome characterized by the presence of symptoms related to SARS-CoV-2 infection that persist for at least four weeks after recovery from COVID-19. Genetics have been proposed to play an important role in long-COVID syndrome onset. This study aimed to identify genetic pathogenetic and likely pathogenetic causative variants of Mendelian genetic diseases in patients with Long-COVID syndrome. Additionally, we aimed to establish an association between these genetic variants and the clinical symptoms manifested during long-COVID syndrome. PATIENTS AND METHODS: 95 patients affected by long-COVID syndrome were analyzed with a Next-Generation Sequencing (NGS) panel comprising 494 genes. The analyzed genes and the symptoms of the patients collected with an ad-hoc questionnaire were divided into four groups (cardiological, respiratory, immunological, and neurological). Finally, a statistical analysis comprising descriptive statistics, classification based on reported symptoms, and comparative analysis against a control group of healthy individuals was conducted. RESULTS: 12 patients resulted positive for genetic testing with an autosomal dominance (8) or autosomal recessive (4) inheritance, showing a higher prevalence of cardiovascular genetic diseases (9) in the analyzed cohort compared to the normal population. Moreover, the onset of the long-COVID syndrome and its cardiovascular manifestations was compliant with the onset reported in the literature for the identified genetic diseases, suggesting that COVID-19 could manifest late-onset genetic diseases associated with their appearance. Apart from the 12 positive patients, 57 were healthy carriers of genetic diseases. Analyzing the whole cohort, a statistical correlation between prevalent symptomatology and the gene class was established, suggesting an association between the genetic susceptibility of an individual and the possibility of developing specific long-COVID syndrome symptoms, especially cardiovascular symptoms. Furthermore, 17 genetic variants were identified in CFTR. Finally, we identified genetic variants in IFNAR2 and POLG, supporting their respective involvement in inflammation and mitochondria mechanisms, correlated with long-COVID syndrome according to literature data. CONCLUSIONS: This study proposed COVID-19 to act as a manifest of underlying late-onset genetic diseases Mendelian associated with carrier status. Moreover, according to our results, mutations in cardiological genes are more present in patients who show cardiological symptoms during the syndrome. This underscores the necessity for cardiological investigation and genetic screening in long-COVID patients to address existing or potential clinical implications.

Autoantibodies in patients with post-COVID syndrome: a possible link with severity?

OBJECTIVE: Coronavirus disease 2019 is an infectious disease associated with the respiratory system caused by the SARS-CoV-2 virus. Right now, an increasing number of patients with Post-COVID Syndrome show, without clear evidence of organ dysfunction, a plethora of severe symptoms, such as fatigue, pain, shortness of breath, cognitive impairment, and sleep disturbance. It has already been demonstrated that SARS-CoV-2 virus can disrupt the self-tolerance mechanism of the immune system, thus triggering autoimmune conditions. Several studies have recently documented the presence of autoantibodies in the sera of post-COVID patients, but until now, it is unclear whether the persistence of symptoms could be directly correlated with the presence of autoantibodies. PATIENTS AND METHODS: In this study, serum autoantibodies (AAbs) levels against four G protein-coupled receptors in 78 patients with post-COVID syndrome have been analyzed. The AAbs investigated are clustered in two groups: adrenergic receptors (α1 and ß2) and muscarinic acetylcholine receptors (M3 and M4). RESULTS: At least one or more AAbs were detected in 60.3% (47/78) of patients diagnosed with post-COVID syndrome, whereas 37.2% (29/78) of patients were positive for all receptors investigated. Interestingly, a strong correlation has been found between AAbs and pain intensity feeling by the patients measured by Visual Analogic Scale. A significant association was also obtained with insomnia and AABS-positive patients. CONCLUSIONS: The identification of AAbs and their correlation with pathological symptoms seriousness underly the possible role of AAbs as future therapeutic targets.

The Role of Olive Tree Polyphenols In The Prevention of COVID-19: A Scoping Review Part 2.

Abstract: The recent COVID-19 pandemic caused by SARS-CoV-2 affected hundreds of millions of people and caused millions of deaths. There are few effective medications against SARS-CoV-2, and several studies attempted to make drugs based on natural components, such as olive leaves. Olive leaves are rich in polyphenolic compounds, which were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. Polyphenols have renown anti-inflammatory and multitarget antiviral effects on several virus families, which could be among the reasons of the beneficial effects of the Mediterranean diet against COVID-19. This scoping review is focused on the effect of olive tree polyphenols as a natural remedy to inhibit SARS-CoV-2, mainly discussing their influence on the process of viral entry into host cells by endocytosis.

The Role of Olive Tree Polyphenols in the Prevention of COVID-19: A Scoping Review, part 1.

Abstract: The global COVID-19 outbreak, started in December 2019, resulted in severe financial losses and extraordinary health crises. Finding a potent and secure medication candidate to treat SARS-CoV-2 infection and its symptoms is still an urgent global need. After reviewing previous studies, olive leaves, being rich in polyphenolic compounds (a large class of bioactive substances naturally found in plants), were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. It has long been known that olive tree polyphenols-such as oleuropein, hydroxytyrosol, verbascoside, as well as triterpenoids like maslinic, ursolic, and oleanolic acids-have anti-inflammatory and multitarget antiviral effects on several virus families, and they could be one of the reasons of the beneficial effects of the Mediterranean diet against COVID-19. Thus, olive tree poly-phenols were tested in silico and in vitro for preventing SARS-CoV-2 infection, claiming that they have beneficial effects. Nevertheless, there is still a small number of research studies on this topic. The aim of this scoping review is to provide more information and offer an opinion on the feasibility of using olive tree polyphenols as a springboard for the creation of innovative natural remedies against this viral illness, ultimately planning future relevant studies.

A Fully Automated, Atlas-Based Approach for Superior Cerebellar Peduncle Evaluation in Progressive Supranuclear Palsy Phenotypes.

BACKGROUND AND PURPOSE: The superior cerebellar peduncle is damaged in progressive supranuclear palsy. However, alterations differ between progressive supranuclear palsy with Richardson syndrome and progressive supranuclear palsy-parkinsonism. In this study, we propose an automated tool for superior cerebellar peduncle integrity assessment and test its performance in patients with progressive supranuclear palsy with Richardson syndrome, progressive supranuclear palsy-parkinsonism, Parkinson disease, and healthy controls. MATERIALS AND METHODS: Structural and diffusion MRI was performed in 21 patients with progressive supranuclear palsy with Richardson syndrome, 9 with progressive supranuclear palsy-parkinsonism, 20 with Parkinson disease, and 30 healthy subjects. In a fully automated pipeline, the left and right superior cerebellar peduncles were first identified on MR imaging by using a tractography-based atlas of white matter tracts; subsequently, volume, mean diffusivity, and fractional anisotropy were extracted from superior cerebellar peduncles. These measures were compared across groups, and their discriminative power in differentiating patients was evaluated in a linear discriminant analysis. RESULTS: Compared with those with Parkinson disease and controls, patients with progressive supranuclear palsy with Richardson syndrome showed alterations of all superior cerebellar peduncle metrics (decreased volume and fractional anisotropy, increased mean diffusivity). Patients with progressive supranuclear palsy-parkinsonism had smaller volumes than those with Parkinson disease and controls and lower fractional anisotropy than those with Parkinson disease. Patients with progressive supranuclear palsy with Richardson syndrome had significantly altered fractional anisotropy and mean diffusivity in the left superior cerebellar peduncle compared with those with progressive supranuclear palsy-parkinsonism. Discriminant analysis with the sole use of significant variables separated progressive supranuclear palsy-parkinsonism from progressive supranuclear palsy with Richardson syndrome with 70% accuracy and progressive supranuclear palsy-parkinsonism from Parkinson disease with 74% accuracy. CONCLUSIONS: We demonstrate the feasibility of an automated approach for extracting multimodal MR imaging metrics from the superior cerebellar peduncle in healthy subjects and patients with parkinsonian. We provide evidence that structural and diffusion measures of the superior cerebellar peduncle might be valuable for computer-aided diagnosis of progressive supranuclear palsy subtypes and for differentiating patients with progressive supranuclear palsy-parkinsonism from with those with Parkinson disease.

Gender effect on non-motor symptoms in Parkinson's disease: are men more at risk?

INTRODUCTION: Several gender differences have been reported in Parkinson's Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their occurrence. METHODS: The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively. RESULTS: 585 PD patients (59.5% men) and 481 controls (34.9% men) were enrolled in the study. All NMS were significantly more frequent among PD patients than controls. PD women showed a significantly higher frequency of depression and urinary disturbances than parkinsonian men; a close frequency among PD women and men was recorded for hallucination, cognitive impairment and sleep disorders. Nonetheless, with respect to the control population, according to logistic regression stratified by sex and adjusted by age, PD men showed a stronger positive significant association with almost all NMS compared to women, excepting for urinary disturbances. The strongest association among PD men was recorded for cognitive impairment (adjusted OR 5.44 for men and 2.82 for women) and depression (adjusted OR 30.88 for men and 12.72 for women). CONCLUSIONS: With respect to the general population, presence of NMS was stronger associated with male gender. Our data suggest that the presence of NMS among PD men is more strictly due to the neurodegenerative processes related to PD.

Characterizing structural neural networks in de novo Parkinson disease patients using diffusion tensor imaging.

Parkinson disease (PD) can be considered as a brain multisystemic disease arising from dysfunction in several neural networks. The principal aim of this study was to assess whether large-scale structural topological network changes are detectable in PD patients who have not been exposed yet to dopaminergic therapy (de novo patients). Twenty-one drug-naïve PD patients and thirty healthy controls underwent a 3T structural MRI. Next, Diffusion Tensor Imaging (DTI) and graph theoretic analyses to compute individual structural white-matter (WM) networks were combined. Centrality (degree, eigenvector centrality), segregation (clustering coefficient), and integration measures (efficiency, path length) were assessed in subject-specific structural networks. Moreover, Network-based statistic (NBS) was used to identify whether and which subnetworks were significantly different between PD and control participants. De novo PD patients showed decreased clustering coefficient and strength in specific brain regions such as putamen, pallidum, amygdala, and olfactory cortex compared with healthy controls. Moreover, NBS analyses demonstrated that two specific subnetworks of reduced connectivity characterized the WM structural organization of PD patients. In particular, several key pathways in the limbic system, basal ganglia, and sensorimotor circuits showed reduced patterns of communications when comparing PD patients to controls. This study shows that PD is characterized by a disruption in the structural connectivity of several motor and non-motor regions. These findings provide support to the presence of disconnectivity mechanisms in motor (basal ganglia) as well as in non-motor (e.g., limbic, olfactory) circuits at an early disease stage of PD. Hum Brain Mapp 37:4500-4510, 2016. © 2016 Wiley Periodicals, Inc.

Tremor pattern differentiates drug-induced resting tremor from Parkinson disease.

OBJECTIVE: DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. METHODS: This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. RESULTS: Rest tremor amplitude was higher in PD patients than in rDIP patients (p < 0.001), while frequency and burst duration were higher in rDIP than in PD (p < 0.001, p < 0.003, respectively). Resting tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p < 0.001). DAT-SPECT was normal in rDIP patients while it was markedly abnormal in patients with PD. CONCLUSIONS: In the absence of DAT-SPECT, the pattern of resting tremor can be considered a useful investigation for differentiating rDIP from PD.

Reduced thalamic volume in Parkinson disease with REM sleep behavior disorder: volumetric study.

INTRODUCTION: REM sleep behavior disorder (RBD) is a common non motor feature of Parkinson's Disease (PD) affecting about half the patients with this disease. Distinct structural brain tissue abnormalities have been reported in several regions modulating REM sleep of the patients with idiopathic RBD. At the present time, there are no conventional MRI studies investigating patients with PD associated with RBD. METHODS: Herein, we used voxel-based morphometry (VBM) to detect the neuroanatomical profile of PD patients with and without RBD. Optimized VBM was applied to the MRI brain images in 11 PD patients with RBD (PD-RBD), 11 PD patients without RBD (PD) and 18 age-and sex-matched controls. To corroborate VBM findings we used automated volumetric method (FreeSurfer) to quantify subcortical brain regions volumes. Patients and controls also underwent DAT-SPECT and cardiac MIBG scintigraphies. RESULTS: The VBM analysis showed markedly reduced gray matter volume in the right thalamus of PD-RBD patients in comparison with PD patients and controls. Automatic thalamic segmentation in PD-RBD patients showed a bilaterally reduced thalamic volume as compared with PD patients or controls. All PD patients (with and without RBD) showed a reduced tracer uptake on DAT-SPECT and cardiac MIBG scintigraphies as compared to controls. CONCLUSIONS: Our findings suggest that the presence of RBD symptoms in PD patients is associated with a reduced thalamic volume suggesting a pathophysiologic role of the thalamus in the complex circuit causing RBD.

Blink reflex recovery cycle distinguishes essential tremor with resting tremor from de novo Parkinson's disease: an exploratory study.

An increased R2 recovery component of the blink reflex (R2-BRrc) has been observed in Parkinson's disease (PD), cranio-cervical dystonia, dystonic tremor and essential tremor with associated resting tremor (rET), while the BRrc was reported normal in patients with essential tremor (ET). Distinguishing rET from tremor dominant PD (tPD) may be challenging especially in the first stages of the diseases, in the absence of DAT-SPECT investigation. We evaluated the possible usefulness of BRrc for differentiating subjects with de novo tPD from those with rET. We investigated R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 ms in 11 participants with tPD, 10 with rET and 20 healthy controls. All participants underwent DAT-SPECT and cardiac MIBG scintigraphy. R2 recovery was significantly enhanced in tPD compared to controls at all investigated ISIs (p < 0.001), while in subjects with rET patients BRrc was significantly increased compared to controls at ISI 150, 200, 300, 400, 500 and 750 ms (p < 0.001). At ISI 100 R2-BRrc distinguished patients participants with de novo tPD from those with rET with a sensitivity, specificity and accuracy of 100%. Our findings demonstrate the usefulness of BRrc for differentiating de novo tPD from rET.

Machine learning on brain MRI data for differential diagnosis of Parkinson's disease and Progressive Supranuclear Palsy.

BACKGROUND: Supervised machine learning has been proposed as a revolutionary approach for identifying sensitive medical image biomarkers (or combination of them) allowing for automatic diagnosis of individual subjects. The aim of this work was to assess the feasibility of a supervised machine learning algorithm for the assisted diagnosis of patients with clinically diagnosed Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP). METHOD: Morphological T1-weighted Magnetic Resonance Images (MRIs) of PD patients (28), PSP patients (28) and healthy control subjects (28) were used by a supervised machine learning algorithm based on the combination of Principal Components Analysis as feature extraction technique and on Support Vector Machines as classification algorithm. The algorithm was able to obtain voxel-based morphological biomarkers of PD and PSP. RESULTS: The algorithm allowed individual diagnosis of PD versus controls, PSP versus controls and PSP versus PD with an Accuracy, Specificity and Sensitivity>90%. Voxels influencing classification between PD and PSP patients involved midbrain, pons, corpus callosum and thalamus, four critical regions known to be strongly involved in the pathophysiological mechanisms of PSP. COMPARISON WITH EXISTING METHODS: Classification accuracy of individual PSP patients was consistent with previous manual morphological metrics and with other supervised machine learning application to MRI data, whereas accuracy in the detection of individual PD patients was significantly higher with our classification method. CONCLUSIONS: The algorithm provides excellent discrimination of PD patients from PSP patients at an individual level, thus encouraging the application of computer-based diagnosis in clinical practice.

MRI measurements predict PSP in unclassifiable parkinsonisms: a cohort study.

OBJECTIVE: Magnetic resonance parkinsonism index (MRPI) has been proposed as a powerful tool to discriminate patients with progressive supranuclear palsy (PSP) from those with Parkinson disease (PD) or other parkinsonisms, on an individual basis. We investigated the usefulness of MRPI in predicting the clinical evolution in PSP of patients with clinically unclassifiable parkinsonism (CUP), i.e., parkinsonism not fulfilling the established clinical diagnostic criteria for any parkinsonian disorders, using a cohort study. METHODS: Forty-five patients with CUP underwent baseline clinical evaluation and MRI with calculation of MRPI. All patients were divided in 2 groups according to MRPI values. A group included 30 patients with CUP with normal MRPI values while the other group included 15 patients with CUP with MRPI values suggestive of PSP (higher than 13.55). A clinical follow-up was performed in all patients. RESULTS: Duration of clinical follow-up in these 2 groups was 28.4 ± 11.7 months (mean ± SD). None of the patients with CUP with normal MRPI values fulfilled established clinical criteria for PSP (follow-up ranging from 24 to 60 months). By contrast, 11 of 15 patients with CUP with abnormal MRPI values (higher than 13.55) developed during the follow-up (range from 6 to 48 months) additional clinical features characteristic of probable (1 patient) or possible (10 patients) PSP. MRPI showed a higher accuracy in predicting PSP (92.9%) than clinical features, such as vertical ocular slowness or first-year falls (61.9% and 73.8%, respectively). CONCLUSIONS: Our findings suggest that MRPI is more powerful than clinical features in predicting the evolution of CUP toward PSP phenotypes.

Association study between the LINGO1 gene and Parkinson's disease in the Italian population.

Some studies have suggested an overlap of clinical and genetic findings between essential tremor (ET) and Parkinson's disease (PD). The first genome-wide association study in ET showed a significant association with the rs9652490 SNP of the leucine-rich repeat and Ig domain containing 1 (LINGO1) gene. Since patients with PD have higher LINGO1 expression levels compared to healthy controls, and animal models of PD show elevated LINGO1 protein levels after experimentally induced damage in the striatum, it can be inferred that LINGO1 is probably involved in PD pathophysiology. In this study, we performed a genetic association analysis of the rs9652490 and rs11856808 SNPs in Italian PD patients and controls to assess the role of these variants in our population. A total of 567 patients with PD and 468 control subjects were enrolled in five Movement Disorder centers located in Central-Southern Italy. Both variants were significantly associated with PD under a recessive model of inheritance before applying the Bonferroni correction. The GG genotype of rs9652490 and the TT genotype of rs11856808 were less frequent in patients than in controls, suggesting a protective effect against the disease. However, after stringent correction, only the P-values obtained from allele and genotype comparisons of the rs11856808 SNP remained significant. Our findings suggest that LINGO1 plays a certain role in the development of PD in the Italian population and represents an interesting candidate gene responsible for PD, due to its involvement in neurological processes.

Novelty seeking and introversion do not predict the long-term risk of Parkinson disease.

OBJECTIVE: It has been suggested that people who develop Parkinson disease (PD) may have a characteristic premorbid personality. We tested this hypothesis using a large historical cohort study with long follow-up. METHODS: We conducted a historical cohort study in the region including the 120-mile radius centered in Rochester, MN. We recruited 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 through 1965 and we considered 5 MMPI scales to measure sensation seeking, hypomania, positive emotionality, social introversion, and constraint. A total of 6,822 subjects (94.5% of the baseline sample) were followed over 4 decades either actively (via interview and examination) or passively (via medical records). RESULTS: During follow-up, 227 subjects developed parkinsonism (156 developed PD). The 3 MMPI scales that we selected to measure the extroverted personality construct (sensation seeking, hypomania, and positive emotionality) did not show the expected pattern of higher scores associated with reduced risk of PD. Similarly, the 2 MMPI scales that we selected to measure the introverted personality construct (social introversion and constraint) did not show the expected pattern of higher scores associated with increased risk of PD. However, higher scores for constraint were associated with an increased risk of all types of parkinsonism pooled together (hazard ratio 1.39; 95% CI 1.06-1.84; p = 0.02). CONCLUSIONS: We suggest that personality traits related to introversion and extroversion do not predict the risk of PD.

Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor.

OBJECTIVE: The aim of our study was to investigate the microstructural integrity of brain regions functionally involved in the tremor loop in patients with familial essential tremor (FET), using diffusion tensor imaging (DTI). METHODS: Twenty-five patients with FET, 15 patients with Parkinson disease (PD), and 15 healthy subjects were studied. DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) in various regions of interest: red nucleus, dentate nucleus (DN), cerebellar white matter, middle (MCP) and superior cerebellar peduncle (SCP), and ventrolateral thalamus. RESULTS: In patients with FET, FA values in the DN (median 0.19, range 0.13-0.23) were reduced (p < 0.001) compared with patients with PD (median 0.37, range 0.32-0.58) and healthy controls (median 0.36, range 0.33-0.40). In patients with FET, FA was also reduced (p = 0.003) and MD values increased (p < 0.001) in the SCP compared with patients with PD and healthy controls. Among patients with FET, those with longer disease duration showed FA values in the DN lower than those with shorter disease duration (p = 0.018). Patients with FET could be completely distinguished from both patient with PD and healthy controls using FA values of the DN alone. CONCLUSION: Neuroimaging evidence of microstructural changes consistent with neurodegeneration was found in the dentate nucleus (DN) and SCP of patients with familial essential tremor. This suggests that neurodegenerative pathology of cerebellar structures may play a role in essential tremor. Further studies are needed to assess the role of fractional anisotropy and mean diffusivity changes in DN and SCP in the differential diagnosis of essential tremor and Parkinson disease, which may present similar clinical signs at the onset of disease.

DJ-1 is a Parkinson's disease susceptibility gene in southern Italy.

Mutations in the gene DJ-1 have been shown to be a rare cause of early-onset Parkinson's disease (EOPD). Since DJ-1 mutations have been found in patients with Parkinson's disease (PD) from southern Italy, we aimed to investigate whether polymorphisms within the DJ-1 gene could represent a risk factor for sporadic PD. First, we genotyped 294 patients with PD and 298 controls coming from southern Italy to assess the distribution of the insertion/deletion (Ins/Del) polymorphism. In a second phase, we identified five single-nucleotide polymorphisms (SNPs) useful to delimit a region potentially involved and genotyped all patients and controls for these markers. All the markers analyzed were significantly associated with PD at both allelic and genotypic level. The most significant association with the disease was found at the Ins/Del polymorphism (p = 0.0001; adjusted odds ratio (OR ) = 2.05; confidence interval (CI ) = 1.36-3.08). When we considered a three-marker sliding window, we found a highly significant association between the disease and the haplotypes including markers rs17523802, Ins/Del, and rs3766606 (p = 0.0007) and markers Ins/Del, rs3766606 and rs7517357 (p = 0.0054). Our results indicate that polymorphisms located in a region spanning 3535 bp from the promoter to the intron 2 of the DJ-1 gene confer risk to sporadic PD in southern Italy.

The DRD2 TaqIA polymorphism associated with changed midbrain volumes in healthy individuals.

The human DRD2 gene is located on chromosome 11q22-q23 and contains one specific functional polymorphism called TaqIA, which characteristically presents two alleles referred to as A1 and A2. Evidence indicates that the A1 allele impacts brain dopaminergic function and may confer an increased risk of developing Parkinson's disease. However, possible morphological changes underlying such genetic variant remain to be clarified. The aim of this study was to provide an in vivo demonstration of changes in brain structures associated with the TaqIA polymorphism of the DRD2 gene. Optimized voxel-based morphometry (VBM) was applied to high-resolution MR brain images of 70 healthy controls divided into two groups according to their DRD2 genotype (A1/A2, n = 15; A2/A2, n = 55). Compared with individuals' homozygous for the A2 allele, the A1 carriers had significantly smaller areas of a specific part of the midbrain, encompassing the substantia nigra bilaterally. Our findings showed an association of the DRD2 TaqIA polymorphism with the changed volumes of a specific subcortical region strongly involved in the dopaminergic system.