Publications by authors named "Paolo Aridon"

46 Publications

Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

Authors:
Maurizio Paciaroni Giancarlo Agnelli Michela Giustozzi Valeria Caso Elisabetta Toso Filippo Angelini Isabella Canavero Giuseppe Micieli Kateryna Antonenko Alessandro Rocco Marina Diomedi Aristeidis H Katsanos Ashkan Shoamanesh Sotirios Giannopoulos Walter Ageno Samuela Pegoraro Jukka Putaala Daniel Strbian Hanne Sallinen Brian C Mac Grory Karen L Furie Christoph Stretz Michael E Reznik Andrea Alberti Michele Venti Maria Giulia Mosconi Maria Cristina Vedovati Laura Franco Giorgia Zepponi Michele Romoli Andrea Zini Laura Brancaleoni Letizia Riva Giorgio Silvestrelli Alfonso Ciccone Maria Luisa Zedde Elisa Giorli Maria Kosmidou Evangelos Ntais Lina Palaiodimou Panagiotis Halvatsiotis Tiziana Tassinari Valentina Saia Raffaele Ornello Simona Sacco Fabio Bandini Michelangelo Mancuso Giovanni Orlandi Elena Ferrari Alessandro Pezzini Loris Poli Manuel Cappellari Stefano Forlivesi Alberto Rigatelli Shadi Yaghi Erica Scher Jennifer A Frontera Luca Masotti Elisa Grifoni Pietro Caliandro Aurelia Zauli Giuseppe Reale Simona Marcheselli Antonio Gasparro Valeria Terruso Valentina Arnao Paolo Aridon Azmil H Abdul-Rahim Jesse Dawson Carlo Emanuele Saggese Francesco Palmerini Boris Doronin Vera Volodina Danilo Toni Angela Risitano Erika Schirinzi Massimo Del Sette Piergiorgio Lochner Serena Monaco Marina Mannino Rossana Tassi Francesca Guideri Maurizio Acampa Giuseppe Martini Enrico Maria Lotti Marina Padroni Leonardo Pantoni Silvia Rosa Pierluigi Bertora George Ntaios Dimitrios Sagris Antonio Baldi Cataldo D'Amore Nicola Mumoli Cesare Porta Licia Denti Alberto Chiti Francesco Corea Monica Acciarresi Yuriy Flomin Nemanja Popovic Georgios Tsivgoulis

Stroke 2021 Mar 4:STROKEAHA120031827. Epub 2021 Mar 4.

Second Department of Neurology, "Attikon" Hospital, National and Kapodistrian University of Athens, School of Medicine, Greece (L. Palaiodimou, G.T.).

Background And Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHADS-VASc and HAS-BLED scores in the same setting.

Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHADS-VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events.

Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHADS-VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468-0.525) and 0.530 (95% CI, 0.500-0.560), respectively.

Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHADS-VASc scores.
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http://dx.doi.org/10.1161/STROKEAHA.120.031827DOI Listing
March 2021

Stroke incidence and case fatality: a 9-year prospective population-based study in an elderly population of Bagheria, Italy.

Neurol Sci 2020 Oct 19. Epub 2020 Oct 19.

Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via Gaetano la Loggia n.1, 90129, Palermo, Italy.

Background: The incidence of stroke in high-income countries has been on the decline; however, few epidemiological surveys have been conducted in recent years to specifically estimate the incidence along with outcome of stroke, in Italy. This study aimed to examine the incidence and case fatality rates of stroke in an elderly Italian population.

Methods: A cohort of 2200 people > 65 years was randomly stratified from the total elderly population of Bagheria, Italy. A 9-year prospective population-based study was performed (19,800 person/years).

Results: We identified 112 first-ever strokes, 53 females and 59 males: 82 (73.1%) ischemic, 13(11.6%) intracerebral haemorrhages, 6 (5.35%) subarachnoid haemorrhages, while 11(9.8%) were classified as undetermined strokes. The crude overall annual incidence was 5.65 per 1000 (95%CI: 4.61 to 6.70) for first-ever stroke. The overall crude incidence rates were 4.74 per 1000 (5.08 for males and 4.46 for females) for ischemic stroke, 0.65 (0.99 for males and 0.37 for females) for intracerebral haemorrhage, and 0.03 for subarachnoid haemorrhage. The incidence rate for first-ever stroke was 5.4 per 1000 (95% CI: 5.36 to 5.45) after adjustment for the 2015 World population and 5.56 (95% CI: 5.52 to 5.61), compared to the 2015 European population. Overall case fatality rates for first-ever stroke was 8.19% at 28 days and 24.1% at 1 year.

Conclusion: Our study shows that in the elderly population investigated, stroke incidence and case fatality rates resulted being lower, compared to those from Italian and most European populations. Similar to previous studies, these rates increased linearly with age and were higher in males.
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http://dx.doi.org/10.1007/s10072-020-04830-7DOI Listing
October 2020

Late seizures in cerebral venous thrombosis.

Neurology 2020 09 5;95(12):e1716-e1723. Epub 2020 Aug 5.

From the Department of Neurology (M.S.v.K., S.M.S., S.M.Z., J.M.C.), Amsterdam UMC, University of Amsterdam, the Netherlands; Department of Clinical Neuroscience (E.L., J.Z., P.R., T.T., K.J.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (E.L., J.Z., P.R., T.T., K.J.), Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurology (S.H., T.T., J.P.), Helsinki University Hospital and University of Helsinki, Finland; Department of Neurology (M.R.H., M.A.), Inselspital, Bern University Hospital and University of Bern, Switzerland; National Institute of Neurology and Neurosurgery Manuel Velasco Suarez (F.S., A.A.), Mexico City, Mexico; Sina Hospital (M.M., M.G.), Hamadan University of Medical Science, Iran; Department of Neurosciences and Mental Health (Neurology) (D.A.d.S., P.C., J.M.F.), Hospital de Santa Maria/CHULN; University of Lisbon (D.A.d.S., P.C., J.M.F.), Portugal; Manchester Centre for Clinical Neurosciences (S.A.-A., M.N.M.P.), Salford Royal NHS Foundation Trust, UK; Department of Neurology (E.E., N.Y.), Istanbul Faculty of Medicine, Istanbul University, Turkey; Neurosciences Department (M.A.B.), Hospital Dr. R.A. Calderón Guardia, CCSS, San José, Costa Rica; and Department of Biomedicine, Neuroscience and Advanced Diagnostics (V.A., P.A.), University of Palermo, Italy.

Objective: To examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT.

Methods: We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS.

Results: We included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0-6.3), 123 patients (11%) experienced ≥1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25-35). Median time to first LS was 5 months (IQR 1-16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9-12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4-7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5-6.5), subdural hematoma (HR 2.3, 95% CI 1.1-4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1-3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS.

Conclusion: During a median follow-up of 2 years, ≈1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS.
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http://dx.doi.org/10.1212/WNL.0000000000010576DOI Listing
September 2020

Acute symptomatic seizures in cerebral venous thrombosis.

Neurology 2020 09 5;95(12):e1706-e1715. Epub 2020 Aug 5.

From the Department of Clinical Neuroscience (E.L., J.Z., P.R., A. Ahmed, T.T., K.J.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (E.L., J.Z., P.R., A. Ahmed, T.T., K.J.), Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurology (S.M.S., S.M.Z., M.S.v.K., J.M.C.), Amsterdam UMC, University of Amsterdam, the Netherlands; Department of Neurology (S.H., T.T., J.P.), Helsinki University Hospital and University of Helsinki, Finland; Department of Neurology (M.R.H., M.A.), Inselspital, Bern University Hospital and University of Bern, Switzerland; National Institute of Neurology and Neurosurgery Manuel Velasco Suarez (F.S., A. Arauz), Mexico City, Mexico; Department of Neurology (M.d.S., T.K.), Royal Adelaide Hospitals and Department of Medicine, University of Adelaide, SA, Australia; Sina Hospital (M.M., M.G.), Hamadan University of Medical Science, Iran; Department of Neurosciences and Mental Health (Neurology) (D.A.d.S., J.M.F.), Hospital de Santa Maria/CHULN; University of Lisbon (D.A.d.S., J.M.F.); Faculdade de Medicina (S.P.), Universidade de Lisboa, Lisbon, Portugal; Manchester Centre for Clinical Neurosciences (S.A.-A., M.N.M.P.), Salford Royal NHS Foundation Trust, UK; Department of Neurology (E.E., N.Y.), Istanbul Faculty of Medicine, Istanbul University, Turkey; Neurosciences Department (M.A.B.), Hospital Dr. R.A. Calderón Guardia, CCSS, San José, Costa Rica; and Department of Biomedicine (V.A., P.A.), Neuroscience and Advanced Diagnostics, University of Palermo, Italy.

Objective: To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium.

Methods: We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression.

Results: Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome.

Conclusion: ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome.
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http://dx.doi.org/10.1212/WNL.0000000000010577DOI Listing
September 2020

Effects of transcranial random noise stimulation combined with Graded Repetitive Arm Supplementary Program (GRASP) on motor rehabilitation of the upper limb in sub-acute ischemic stroke patients: a randomized pilot study.

J Neural Transm (Vienna) 2019 12 1;126(12):1701-1706. Epub 2019 Oct 1.

Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), University of Palermo, Via Gaetano La Loggia n.1, 90129, Palermo, Italy.

We evaluated the combined use of transcranial random noise stimulation (tRNS) with the Graded Repetitive Arm Supplementary Program (GRASP) in sub-acute ischemic stroke patients suffering from arm impairment. Eighteen ischemic stroke patients with upper limb disability were randomly assigned to either the GRASP + tRNS or GRASP + Sham stimulation group. Fugl-Meyer Assessment-Upper extremity (FMA-UE) was performed to evaluate upper limb impairment before treatment (T0), after the last stimulation (T1) and after 30 days (T2). At T1 and T2, beneficial effects in the tRNS group correlated with better FMA-UE score than sham stimulation group (p < 0.001) and these results did not correlate to stroke severity, because no associations were observed between National Institute of Health Stroke Scale and FMA UE T1 and T2. This study displayed a good feasibility and was the first to evaluate the use of tRNS in association with Grasp in sub-acute stroke survivors having arm impairment to improve arm motor recovery.
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http://dx.doi.org/10.1007/s00702-019-02087-9DOI Listing
December 2019

TBC1D24-TLDc-related epilepsy exercise-induced dystonia: rescue by antioxidants in a disease model.

Brain 2019 08;142(8):2319-2335

Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Florence, Italy.

Genetic mutations in TBC1D24 have been associated with multiple phenotypes, with epilepsy being the main clinical manifestation. The TBC1D24 protein consists of the unique association of a Tre2/Bub2/Cdc16 (TBC) domain and a TBC/lysin motif domain/catalytic (TLDc) domain. More than 50 missense and loss-of-function mutations have been described and are spread over the entire protein. Through whole genome/exome sequencing we identified compound heterozygous mutations, R360H and G501R, within the TLDc domain, in an index family with a Rolandic epilepsy exercise-induced dystonia phenotype (http://omim.org/entry/608105). A 20-year long clinical follow-up revealed that epilepsy was self-limited in all three affected patients, but exercise-induced dystonia persisted into adulthood in two. Furthermore, we identified three additional sporadic paediatric patients with a remarkably similar phenotype, two of whom had compound heterozygous mutations consisting of an in-frame deletion I81_K84 and an A500V mutation, and the third carried T182M and G511R missense mutations, overall revealing that all six patients harbour a missense mutation in the subdomain of TLDc between residues 500 and 511. We solved the crystal structure of the conserved Drosophila TLDc domain. This allowed us to predict destabilizing effects of the G501R and G511R mutations and, to a lesser degree, of R360H and potentially A500V. Next, we characterized the functional consequences of a strong and a weak TLDc mutation (TBC1D24G501R and TBC1D24R360H) using Drosophila, where TBC1D24/Skywalker regulates synaptic vesicle trafficking. In a Drosophila model neuronally expressing human TBC1D24, we demonstrated that the TBC1D24G501R TLDc mutation causes activity-induced locomotion and synaptic vesicle trafficking defects, while TBC1D24R360H is benign. The neuronal phenotypes of the TBC1D24G501R mutation are consistent with exacerbated oxidative stress sensitivity, which is rescued by treating TBC1D24G501R mutant animals with antioxidants N-acetylcysteine amide or α-tocopherol as indicated by restored synaptic vesicle trafficking levels and sustained behavioural activity. Our data thus show that mutations in the TLDc domain of TBC1D24 cause Rolandic-type focal motor epilepsy and exercise-induced dystonia. The humanized TBC1D24G501R fly model exhibits sustained activity and vesicle transport defects. We propose that the TBC1D24/Sky TLDc domain is a reactive oxygen species sensor mediating synaptic vesicle trafficking rates that, when dysfunctional, causes a movement disorder in patients and flies. The TLDc and TBC domain mutations' response to antioxidant treatment we observed in the animal model suggests a potential for combining antioxidant-based therapeutic approaches to TBC1D24-associated disorders with previously described lipid-altering strategies for TBC domain mutations.
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http://dx.doi.org/10.1093/brain/awz175DOI Listing
August 2019

Urological dysfunctions in patients with Parkinson's disease: clues from clinical and non-invasive urological assessment.

BMC Neurol 2018 Sep 20;18(1):148. Epub 2018 Sep 20.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNeC), Università degli studi Palermo, Via Gaetano La Loggia 1, 90129, Palermo, Italy.

Background: Autonomic nervous system dysfunction, common in patients with Parkinson's disease (PD), causes significant morbidity and it is correlated with poor quality of life. To assess frequency of urinary symptoms in patients with PD, without conditions known to interfere with urinary function.

Methods: Non-demented PD patients were consecutively enrolled from the outpatients clinic of our department. Scales investigating motor and non-motor symptoms were carried out. Evaluation of urinary dysfunctions was carried out using the AUTonomic Scale for Outcomes in Parkinson's disease (SCOPA-AUT) questionnaire. Patients underwent noninvasive urological studies (nUS), including uroflowmetry and ultrasound of the urinary tract.

Results: Forty-eight (20 women, 42%) out of 187 PD patients met the inclusion criteria and were enrolled in the study. Mean SCOPA-AUT score was 14.1 ± 6.9 (urinary symptoms subscore 5.2 ± 3.8). Among those evaluated by the SCOPA-AUT scale, the urinary symptoms were among the most common complaints (93.8%). At nUS mean maximum flow rate (Qmax) was 17.9 ± 9.1 ml/s, and mean postvoid residual (PVR) urine volume was 24.4 ± 44.1 ml. Ultrasound investigation documented prostate hypertrophy in 12 male patients (42.8%). Urinary items of the SCOPA-AUT (SCOPA-U subscore) correlated with measures of disease severity only in female patients.

Conclusion: Urinary symptoms and abnormal findings in nUS are common in PD. Though nigrostriatal degeneration might be responsible for urinary symptoms also in the early-intermediate stage of the disease, when urinary dysfunction occurs other medical conditions need to be excluded.
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http://dx.doi.org/10.1186/s12883-018-1151-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146523PMC
September 2018

Doege-Potter syndrome: When seizures and hypoglycemia collide.

Iran J Neurol 2018 Apr;17(2):86-88

Department of Experimental Biomedicine, Neuroscience Clinic, University of Palermo, Palermo, Italy.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131338PMC
April 2018

Frequency and determinants for hemorrhagic transformation of posterior cerebral stroke : Posterior ischemic stroke and hemorrhagic transformation.

BMC Res Notes 2017 Nov 13;10(1):592. Epub 2017 Nov 13.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNeC), Università degli Studi di Palermo, Via Gaetano La Loggia 1, 90129, Palermo, Italy.

Background: hemorrhagic transformation is a threatening ischemic stroke complication. Frequency of hemorrhagic transformation differs greatly among studies, and its risk factors have been usually studied in patients with anterior ischemic stroke who received thrombolytic therapy. We evaluated, in a hospital-based series of patients with posterior ischemic stroke not treated with thrombolysis, frequency and risk factors of hemorrhagic transformation. Patients with posterior circulation stroke were seen in our Department during the period January 2004 to December 2009. Demographic and clinical information were collected. We estimated risk for spontaneous hemorrhagic transformation by means of uni- and multivariate logistic regression analyses.

Results: 119 consecutive patients were included (73 males, 61.3%). Hemorrhagic transformation was observed in 7 patients (5.9%). Only clinical worsening was significantly associated with hemorrhagic transformation (OR 6.8, 95% CI 1.3-34.5).

Conclusions: Our findings indicate that patients with posterior have a low risk of spontaneous hemorrhagic transformation, suggesting that these patients might have greater advantage from intravenous thrombolysis.
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http://dx.doi.org/10.1186/s13104-017-2889-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683579PMC
November 2017

Association between multiple sclerosis, cancer risk, and immunosuppressant treatment: a cohort study.

BMC Neurol 2017 Aug 8;17(1):155. Epub 2017 Aug 8.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (Department of Experimental Biomedicine and Clinical Neurosciences), Università degli Studi di Palermo, Via G. La Loggia, 1, 90129, Palermo, Italy.

Background: The association between multiple sclerosis (MS) and cancer has long been investigated with conflicting results. Several reports suggest an increased cancer risk among MS patients treated with immunosuppressant (IS) drugs.

Methods: We performed a cohort study including MS patients recruited at the Neurological Department of the University of Palermo. Mean follow-up period was ten years for the whole cohort. We calculated cancer incidence among patients treated with IS. Incidence rates were compared in the cohort by calculating the relative risk according to length and dose of exposure to IS. Cancer incidence among MS patients was compared to cancer incidence in the general population of Sicily in similar age groups.

Results: On an overall cohort of 531 MS patients (346 women and 185 men) exposed to IS, we estimated a crude incidence rate for cancer of 2.26% (2.02% in women, 2.7% in men). Cancer risk was higher compared to rates observed among an equal number of patients not exposed to IS, and to the risk in the general population in Sicily at similar age groups (adjusted HR: 11.05; CI 1.67-73.3; p = 0.013).

Conclusion: The present study showed a higher cancer risk in MS patients associated only to previous IS exposure. Studies on long-term outcomes are essential to evaluate the possibility that treatment options that need to be considered for a long time-period may modify risk for life threatening diseases.
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http://dx.doi.org/10.1186/s12883-017-0932-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549380PMC
August 2017

Seizure following the Use of the COX-2 Inhibitor Etoricoxib.

Case Rep Neurol Med 2017 22;2017:1410759. Epub 2017 Jan 22.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy.

We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. . Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.
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http://dx.doi.org/10.1155/2017/1410759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292120PMC
January 2017

New frontiers in anticoagulation: non vitamin-K oral anticoagulants in stroke prevention.

Expert Rev Neurother 2017 06 12;17(6):539-552. Epub 2016 Dec 12.

a BioNeC Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche , Università degli Studi di Palermo , Palermo , Italy.

Introduction: Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists. New evidences have suggested their use in treatment of elderly people, in patients with renal insufficiency or with antiphospholipid antibody syndrome. In addition, the use of antidotes, which rapidly reverse the anticoagulant effect of the NOACs, could be useful in bleeding, during emergency procedures, or in case of overdose.
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http://dx.doi.org/10.1080/14737175.2017.1268053DOI Listing
June 2017

Mercaptopurine Treatment in an Adult Man with Orbital and Intracranial Rosai-Dorfman Disease.

Case Rep Neurol Med 2016 20;2016:1030478. Epub 2016 Oct 20.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy.

. Rosai-Dorfmann disease (RDD) is a rare, idiopathic non-Langerhans cell histiocytosis, affecting children and young adults, that commonly presents as painless, massive cervical lymphadenopathy with fever, weight loss, and polyclonal hypergammaglobulinemia. Cervical lymphadenopathy and extranodal involvement are the main presentations. On the contrary, ophthalmic involvement and localisation in the central nervous system are rare. . An old man was admitted to our hospital for first seizure. Brain imaging studies revealed on the left an extra-axial thickening of the dura mater with enhancement and perilesional oedema, infiltrating the sphenoorbital fissure and an isointense mass with enhancement in the orbital region with dislocation of the optic nerve. Pathological and immunohistochemistry examination of the bioptical specimen was consistent with a diagnosis of RDD. Treatment with levetiracetam and steroids was started obtaining only remission of seizures. Because of the patient refusal of the surgical debulking, therapy with mercaptopurine was started, stopping disease progression. . So far, very few cases of extranodal RDD with multiple CNS lesions involving the orbital region have been described. Our case is significant because it is the first case in which the efficacy of mercaptopurine treatment has been documented in an adult patient with isolated ocular and intracranial RDD.
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http://dx.doi.org/10.1155/2016/1030478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093240PMC
October 2016

A TRAPPC6B splicing variant associates to restless legs syndrome.

Parkinsonism Relat Disord 2016 10 18;31:135-138. Epub 2016 Aug 18.

Vita-Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy. Electronic address:

Introduction: RLS is a common movement disorders with a strong genetic component in its pathophysiology, but, up to now, no causative mutation has been reported.

Methods: We re-evaluated the previously described RLS2 family by exome sequencing.

Results: We identified fifteen variations in the 14q critical region. The c.485G > A transition of the TRAPPC6B gene segregates with the RLS2 haplotype, is absent in 200 local controls and is extremely rare in 12988 exomes from the Exome Variant Server (EVS). This variant alters a splicing site and hampers the normal transcript processing by promoting exon 3-skipping as demonstrated by minigene transfection and by patient transcripts.

Conclusions: We identified a TRAPPC6B gene mutation associated to the RLS locus on chromosome 14.
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http://dx.doi.org/10.1016/j.parkreldis.2016.08.016DOI Listing
October 2016

Corticobasal syndrome-like variant of Creutzfeldt-Jakob disease: clinical description of two cases.

Neurol Sci 2015 Jul 17;36(7):1303-5. Epub 2014 Dec 17.

Dipartimento di BioMedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Via Gaetano La Loggia n.1, 90144, Palermo, Italy,

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http://dx.doi.org/10.1007/s10072-014-2043-7DOI Listing
July 2015

Early and late mortality of spontaneous hemorrhagic transformation of ischemic stroke.

J Stroke Cerebrovasc Dis 2014 Apr 5;23(4):649-54. Epub 2013 Jul 5.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy.

Background: Hemorrhagic transformation (HT), a complication of ischemic stroke (IS), might influence patient's prognosis. Our aim is to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between HT and mortality.

Methods: We compared mortality of individuals with spontaneous HT with that of individuals without. Medical records of patients diagnosed with anterior IS were retrospectively reviewed. Outcome measures were 30- and 90-day survival after IS onset. Kaplan-Meier estimates were used to construct survival curves. Cox proportional hazards model was used to estimate hazard ratio (HR) for the main outcome measure (death). HT was stratified in hemorrhagic infarction and parenchymal hematoma (PH). We also evaluated the relationship between HT and the main mortality risk factors (gender, age, premorbid status, severity of stroke, and radiological features).

Results: Thirty days from stroke onset, 8.1% (19 of 233) of patients died. At multivariate analysis, PH (HR: 7.7, 95% confidence interval [CI]: 2.1, 27.8) and low level of consciousness at admission (HR: 5.0, 95% CI: 1.3, 18.6) were significantly associated with death. At 3-month follow-up, mortality rate was 12.1% (28 of 232). At multivariate analysis, large infarct size (HR: 2.7, 95% CI: 1.2, 6.0) and HT (HR: 2.3, 95% CI: 1.0, 5.4) were independent risk factors for mortality. Parenchymal hematoma was, however, the strongest predictor of late mortality (HR: 7.9, 95% CI: 2.9, 21.4).

Conclusions: Neurological status and infarct size play a significant role, respectively, in early and late mortality after IS. Parenchymal hematoma independently predicts both early and late mortality.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.06.005DOI Listing
April 2014

Tumor diagnosis preceding Alzheimer's disease onset: is there a link between cancer and Alzheimer's disease?

J Alzheimers Dis 2012 ;31(1):177-82

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università di Palermo, Palermo, Italy.

Studies reporting an inverse association between Alzheimer's disease (AD) and cancer are scant. Available data are mostly based on ancillary findings of mortality data or obtained from studies evaluating frequency of neoplasms in AD patients independently if they occurred before or after AD. Moreover, some studies estimated frequencies of neoplasms in demented individuals, who were not necessarily AD patients. We estimated frequency of tumors preceding the onset of AD in AD patients and compared it to that of age- and gender-matched AD-free individuals. Occurrence of tumors preceding AD onset was assessed through a semi-structured questionnaire. Tumors were categorized as benign, malignant, or of uncertain classification and as endocrine-related or not. Odds ratios (OR), used as measure of the association between the two diseases, were adjusted for tumor categories and known risk factors for AD and tumors. We included 126 AD patients and 252 matched controls. Tumor frequency before AD onset was 18.2% among cases and 24.2% among controls. There was a suggestive trend of an overall inverse association between the two diseases (adjusted OR 0.6; 95% CI 0.4-1.1; p = 0.11). Risk for neoplasms was significantly reduced only for women (adjusted OR, 0.5; 95% CI 0.3-0.9; p = 0.03) and for endocrine related tumors (adjusted OR, 0.5; 95% CI 0.2-1; p = 0.04). Our study confirms the inverse association reported in previous epidemiological studies. Though our findings might be explained by processes playing an opposite role in tumors development and neurodegeneration, they are also suggestive for a possible role of estrogen.
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http://dx.doi.org/10.3233/JAD-2012-120184DOI Listing
December 2012

Incidence of amyotrophic lateral sclerosis in Sicily: A population based study.

Amyotroph Lateral Scler 2012 May 13;13(3):284-7. Epub 2012 Mar 13.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche.

Our objective was to investigate incidence of amyotrophic lateral sclerosis (ALS) in Sicily, southern Italy, by means of a population based study. We included people with ALS resident in five Sicilian provinces, whose onset occurred in the two-year period 2005-2006 (population at 31 December 2006: 3,481,096 inhabitants). A multisource case-finding procedure was adopted and patients were classified as affected by ALS according to revised El Escorial criteria. During the two-year surveillance period, 97 patients meeting eligibility criteria included 57 males (58.8%) and 40 females (41.2%). Crude annual incidence rate was 1.4/100,000 person years (95% CI 1.33-1.47). The incidence rate was higher in males (1.71/100,000; CI 1.61-1.81) than in females (1.11/100,000; CI 1.01-1.21). Standardized incidence rate for the total population in the 45-74-years-old age group was 3.22 (CI 3.11-3.33). Prevalence rate was 6.0/100,000 (CI 5.97-6.03), higher in males (7.1/100,000; CI 7.02-7.18) than females (4.9/100,000; CI 4.86-4.94). In conclusion, ALS rates observed in the present study are higher in males than females, with a peak of incidence at 70 years of age in both genders. These findings are consistent with those of other population based European studies.
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http://dx.doi.org/10.3109/17482968.2012.662689DOI Listing
May 2012

Cholesterol levels and risk of hemorrhagic transformation after acute ischemic stroke.

Cerebrovasc Dis 2011 23;32(3):234-8. Epub 2011 Aug 23.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, University of Palermo, Palermo, Italy.

Background: The association between cholesterol levels and hemorrhagic transformation (HT) is still controversial. Studies investigating this issue are influenced by treatments as some are characterized by a higher risk of HT. The aim of our study was to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between cholesterol levels and HT.

Methods: We retrospectively collected information about total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels at admission in a consecutive series of 240 patients with anterior ischemic stroke (IS). The TC and LDLC levels were arranged in 3 groups according to their percentile distribution.

Results: TC levels were available for 215 patients (89.6%), while LDLC levels were available for 184 patients (76.7%). The risk of HT significantly increased with decreasing levels of TC (p for trend = 0.03) and LDLC (p for trend = 0.01). In multivariate analysis, the risk of HT was significantly higher in the groups of patients with the lowest TC (OR 2.8, 95% CI 1.0-8.9, p = 0.05) and LDLC (OR 5.0, 95% CI 1.2-20.1, p = 0.002) values compared to those with the highest ones.

Conclusion: We confirm that lower TC and lower LDLC levels are associated with an increased risk of HT. As none of our patients received thrombolytic therapy, the results of our study provide baseline information about the natural history of HT.
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http://dx.doi.org/10.1159/000329315DOI Listing
January 2012

A population-based survey of cognitive performance in a Sicilian elderly community.

Neuroepidemiology 2011 5;36(3):169-76. Epub 2011 May 5.

Dipartimento Universitario di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italia.

Background: The global burden of neurodegenerative diseases is increasing. Previous studies reported differences related to age, gender and socioeconomic status. We calculated the cognitive performances of a Sicilian population aged 65 years or older, by means of a door-to-door population-based survey in Bagheria city, Sicily.

Methods: A door-to-door survey was carried out in the city of Bagheria, Sicily (prevalence day September 30, 2006). A cohort of 2,200 persons was randomly stratified, obtaining a 25% sample of the whole population. Cognitive function was assessed by Mini Mental State Examination (MMSE). Percentile distributions by age, gender, education and working activity were calculated. Regression models were used to analyze the relationship between the investigated variables and cognitive performance.

Results: A total of 1,837 persons agreed to participate (1,062 women and 775 men). Distribution of MMSE showed a highly significant inverse linear trend related to the increasing age (p < 0.0001) and to the degree of education (p < 0.0001), both in men and women. We observed a significant association between higher education and a better cognitive performance (OR 6.91; CI 3.24-14.76) and an inverse association between manual kind of occupation versus not manual and a poorer cognitive status (OR 0.82; CI 0.67-0.997). Height was associated with decreased cognitive performances in women (OR = 1.03; CI = 1.01-1.05) but not in men (OR = 0.997; CI = 0.993-1.002).

Conclusions: These findings provide a feature of cognitive performances in Sicily, measured by MMSE scores in individuals aged 65 years or older.
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http://dx.doi.org/10.1159/000326065DOI Listing
May 2012

Reversible posterior leukoencephalopathy syndrome in a patient with thrombotic thrombocytopenic purpura.

Neurol Sci 2011 Jun 14;32(3):469-72. Epub 2011 Jan 14.

Biomedicina Sperimentale e Neuroscienze Cliniche, University of Palermo, Via Gaetano La Loggia 1, 90129 Palermo, Italy.

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterised by fever, microangiopathic haemolytic anaemia, renal insufficiency, and thrombocytopenia. Neurological involvement, a prominent component of TTP, is characterised by a variety of brain lesions which include reversible cerebral oedema or magnetic resonance imaging (MRI) features of reversible posterior leukoencephalopathy syndrome (RPLS). TTP is frequently associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13.Here, we report a case of TTP with severe acute encephalopathy. Posterior leukoencephalopathy and brainstem oedema with triventricular hydrocephalus were observed on MRI. The low activity of ADAMTS13 was not observed and ADAMTS-13 antibodies were absent. Neurological symptoms and patient's condition were completely resolved by plasma exchange therapy in addition to high dose of methylprednisolone.
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http://dx.doi.org/10.1007/s10072-010-0465-4DOI Listing
June 2011

Protective role of heat shock proteins in Parkinson's disease.

Neurodegener Dis 2011 5;8(4):155-68. Epub 2011 Jan 5.

Biomedicina Sperimentale e Neuroscienze Cliniche, Alberto Monroy, Università di Palermo, Palermo, Italia.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Despite a large amount of research, the pathogenetic mechanism of these diseases has not yet been clarified. Abnormal protein folding, oxidative stress, mitochondrial dysfunction, and apoptotic mechanisms have all been reported as causes of neurodegenerative diseases in association with neuroinflammatory mechanisms which, by generating deleterious molecules, could promote the cascade of events leading to neurodegeneration. Heat shock proteins (HSPs) play a central role in preventing protein misfolding and inhibiting apoptotic activity, and represent a class of proteins potentially involved in PD pathogenesis. The present review will focus on two HSPs, HSP70 and HSP90, with the aim of specifying their role in PD pathogenesis.
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http://dx.doi.org/10.1159/000321548DOI Listing
October 2011

MRI abnormalities following repeated and incoming seizures.

Seizure 2011 Jan 12;20(1):90-2. Epub 2010 Oct 12.

Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, University of Palermo, Via Gaetano La Loggia 1, 90129 Palermo, Italy.

Neuroimaging, an important diagnostic tool frequently used in the evaluation of patients with epilepsy, has mainly the aim to identify structural abnormalities needing a treatment and to contribute to the definition of the aetiology. Brain magnetic resonance imaging (MRI) in epilepsy is more sensitive than computerized tomography (CT) scan for detecting abnormalities. Status epilepticus (SE) and repeated incoming seizures may determine extensive and transient or long lasting pronounced MRI changes. We describe a case of a 41-year-old woman with a history of brain neoplasm, whose contrast-enhanced MRI images following repeated and incoming seizures were characterized either by reversible and irreversible abnormalities.
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http://dx.doi.org/10.1016/j.seizure.2010.09.012DOI Listing
January 2011

Relapsing or refractory idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the role of rituximab.

Transfusion 2010 Dec;50(12):2753-60

Cattedra ed U.O. di Ematologia con trapianto, U.O. di Immunoematologia e Servizio Trasfusionale, and U.O. di Neurologia, Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone di Palermo, Palermo, Italy.

Idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare disease responsive to treatment with plasma exchange (PE) but with a high percentage of relapse or refractory patients. A severe deficiency of ADAMTS-13 (<5% of normal activity), congenital or caused by an autoantibody, may be specific for TTP and it has been proposed that severe ADAMTS-13 deficiency now defines TTP. B cells play a key role in both the development and the perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with idiopathic TTP-HUS. This review of the literature focuses on the role of rituximab, a chimeric monoclonal antibody directed against CD20 antigen expressed by B lymphocytes, in patients with relapsing or refractory TTP-HUS with or without ADAMTS-13 deficiency, suggesting that rituximab may produce clinical remission in a significant proportion of patients. Rituximab therapy reduces plasma requirement and avoids complications related to salvage-immunosuppressive therapy. In conclusion, rituximab provides an effective, well-tolerated, and safe treatment option for patients with idiopathic TTP-HUS, thus giving an alternative approach to the current treatment based on PE.
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http://dx.doi.org/10.1111/j.1537-2995.2010.02763.xDOI Listing
December 2010

Leprosy: report of a case with severe peripheral neuropathy.

Neurol Sci 2010 Feb 8;31(1):75-7. Epub 2009 Oct 8.

Dipartimento Universitario di Neuroscienze Cliniche (DiNeC), University of Palermo, Via Gaetano La Loggia 1, 90129, Palermo, Italy.

Leprosy (Hansen's disease) is a chronic granulomatous infectious disease, caused by Mycobacterium leprae, with cutaneous and neurological manifestations. Leprosy is very rare in Europe but some cases are reported, especially among people coming from endemic areas. Here, we report a case of Hansen's disease and emphasize the importance of a prompt diagnosis and treatment also in non-endemic areas.
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http://dx.doi.org/10.1007/s10072-009-0152-5DOI Listing
February 2010

Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation.

Neurol Sci 2009 Dec 25;30(6):527-9. Epub 2009 Sep 25.

Department of Clinical Neuroscience, University of Palermo, Via Gaetano La Loggia 1, 90129 Palermo, Italy.

Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.
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http://dx.doi.org/10.1007/s10072-009-0149-0DOI Listing
December 2009

Frequency and determinants for hemorrhagic transformation of cerebral infarction.

Neuroepidemiology 2009 27;33(3):261-5. Epub 2009 Jul 27.

Dipartimento di Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy.

Background: Frequency and associated risk factors for hemorrhagic transformation (HT), a worrying complication of ischemic stroke (IS), are not clearly defined. Our aim was to estimate the overall frequency and risk factors for HT in a hospital-based population.

Methods: A retrospective review of medical records of patients discharged from our department during the period 2004-2006 with a diagnosis of anterior IS. Demographic, clinical and hematological information was collected. Uni- and multivariate logistic regression analyses were used to estimate risk for spontaneous HT.

Results: We included 240 patients (125 males, 52%), mean age at admission was 72.5 years. HT was observed in 29 patients (12%). At univariate analysis, consciousness impairment at admission (OR 5.6, 95% CI 1.3-28.2), the presence of early CT signs (OR 2.4, 95% CI 1.1-5.3), infarcts of medium-large size (OR 11.3, 95% CI 4.1-30.8), cardioembolic stroke (OR 2.3, 95% CI 1.1-5.2) and low total cholesterol levels (OR 3.3, 95% CI 1.3-8.2) were significantly associated with HT. At multivariate analysis, only infarct size (OR 10.2, 95% CI 3.2-32.1) was still significantly associated with HT.

Conclusions: Frequency of HT in our study was 12%. Consistently with previous results, HT was associated with the size of ischemic area. As patients included in our study did not receive thrombolytic therapy, our results are applicable to those patients whom clinicians, working in a hospital setting, usually deal with.
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http://dx.doi.org/10.1159/000229781DOI Listing
May 2010

Diabetes preceding Parkinson's disease onset. A case-control study.

Parkinsonism Relat Disord 2009 Nov 7;15(9):660-4. Epub 2009 Apr 7.

Dipartimento Universitario di Neuroscienze Cliniche, Via Gaetano La Loggia 1, 90129 Palermo, Italy.

Objective: To assess the association between diabetes preceding Parkinson's disease (PD) and PD.

Methods: PD individuals were matched to PD free individuals randomly selected from people in the same municipality as the cases. Occurrence of diabetes preceding PD onset among cases and controls was assessed through a structured questionnaire. Information regarding current and past medical treatment and other variables was also collected. We used univariate and multivariate logistic models to calculate crude and adjusted odds ratios (OR). Covariates are adjusted for included education, smoking habit, alcohol and coffee consumption.

Results: 318 PD individuals (165 women, 153 men) and 318 matched controls were included in the study. PD patients had a mean age at interview of 66.7 years. Mean age at PD onset was 60.8 years and mean PD duration 5.9 years. We found an inverse association between PD and diabetes preceding PD onset in all groups stratified by gender, age at PD onset, body mass index (BMI), smoking habit, alcohol and coffee consumption. Multivariate analysis yielded the same findings after controlling for the variables (adjusted OR 0.4; 95% CI, 0.2-0.8).

Conclusions: Our findings provide additional support for a potential link between diabetes and PD.
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http://dx.doi.org/10.1016/j.parkreldis.2009.02.013DOI Listing
November 2009