39 results on '"Daniele, Cazzato"'
Search Results
2. Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies
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Rowida Almomani, Maurice Sopacua, Margherita Marchi, Milena Ślęczkowska, Patrick Lindsey, Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Erika Salvi, Ingemar S. J. Merkies, Maryam Ferdousi, Rayaz A. Malik, Dan Ziegler, Kasper W. J. Derks, Gidon Boenhof, Filippo Martinelli-Boneschi, Daniele Cazzato, Raffaella Lombardi, Sulayman Dib-Hajj, Stephen G. Waxman, Hubert J. M. Smeets, Monique M. Gerrits, Catharina G. Faber, Giuseppe Lauria, and on behalf of the PROPANE Study Group
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diabetic neuropathy ,small fiber neuropathy ,neuropathic pain ,molecular inversion probes ,next generation sequencing ,sodium channel genes variants ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Neuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium channel genes (SCG) expressed in a nociceptive pathway in painful and painless DPN and painful and painless SFN patients, and to provide a perspective for clinicians who assess patients with painful peripheral neuropathy. Between June 2014 and September 2016, 1125 patients with painful-DPN (n = 237), painless-DPN (n = 309), painful-SFN (n = 547) and painless-SFN (n = 32), recruited in four different centers, were analyzed for SCN3A, SCN7A-SCN11A and SCN1B-SCN4B variants by single molecule Molecular inversion probes-Next Generation Sequence. Patients were grouped based on phenotype and the presence of SCG variants. Screening of SCN3A, SCN7A-SCN11A, and SCN1B-SCN4B revealed 125 different (potential) pathogenic variants in 194 patients (17.2%, n = 194/1125). A potential pathogenic variant was present in 18.1% (n = 142/784) of painful neuropathy patients vs. 15.2% (n = 52/341) of painless neuropathy patients (17.3% (n = 41/237) for painful-DPN patients, 14.9% (n = 46/309) for painless-DPN patients, 18.5% (n = 101/547) for painful-SFN patients, and 18.8% (n = 6/32) for painless-SFN patients). Of the variants detected, 70% were in SCN7A, SCN9A, SCN10A and SCN11A. The frequency of SCN9A and SCN11A variants was the highest in painful-SFN patients, SCN7A variants in painful-DPN patients, and SCN10A variants in painless-DPN patients. Our findings suggest that rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification should aid in a better understanding of the genetic variability in patients with painful and painless neuropathy, and may lead to better risk stratification and the development of more targeted and personalized pain treatments.
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- 2023
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3. SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy.
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Tommaso Gili, Giampaolo Benelli, Elisabetta Buscarini, Ciro Canetta, Giuseppe La Piana, Guido Merli, Alessandro Scartabellati, Giovanni Viganò, Roberto Sfogliarini, Giovanni Melilli, Roberto Assandri, Daniele Cazzato, Davide Sebastiano Rossi, Susanna Usai, Guido Caldarelli, Irene Tramacere, Germano Pellegata, and Giuseppe Lauria
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Medicine ,Science - Abstract
We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (67.7% males) median age was 70.8 years (range 5-99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60-69 years old, 21.1% in 70-79 years old, 38.8% in 80-89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Charlson comorbidity index and high C-reactive protein at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1-98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% accuracy. Comorbidity network analysis revealed a more homogenous distribution 60-40 aged SARS-COV-2 patients across diseases and a crucial different interplay of diseases in the networks of deceased and survived patients. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre-existing multiorgan impairment.
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- 2021
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4. Network topology of NaV1.7 mutations in sodium channel-related painful disorders.
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Dimos Kapetis, Jenny Sassone, Yang Yang 0049, Barbara Galbardi, Markos N. Xenakis, Ronald L. Westra, Radek Szklarczyk, Patrick Lindsey, Catharina G. Faber, Monique Gerrits, Ingemar S. J. Merkies, Sulayman D. Dib-Hajj, Massimo Mantegazza, Stephen G. Waxman, Giuseppe Lauria, Michela Taiana, Margherita Marchi, Raffaella Lombardi, Daniele Cazzato, Filippo Martinelli-Boneschi, Andrea Zauli, Ferdinando Clarelli, Silvia Santoro, Ignazio Lopez, Angelo Quattrini, Janneke Hoeijmakers, Maurice Sopacua, Bianca de Greef, Hubert J. M. Smeets, Rowida Al Momani, Jo Michel Vanoevelen, Ivo Eijkenboom, Sandrine Cestèle, Oana Chever, Rayaz A. Malik, Mitra Tavakoli, and Dan Ziegler
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- 2017
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5. PLIN4-related myopathy: clinical, histological and imaging data in a large cohort of patients
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Lorenzo Maggi, Sara Gibertini, Eliana Iannibelli, Annamaria Gallone, Silvia Bonanno, Daniele Cazzato, Simonetta Gerevini, Marco Moscatelli, Flavia Blasevich, Giorgia Riolo, Renato Mantegazza, and Alessandra Ruggieri
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Neurology ,Neurology (clinical) - Published
- 2023
6. Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies
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Group, Rowida Almomani, Maurice Sopacua, Margherita Marchi, Milena Ślęczkowska, Patrick Lindsey, Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Erika Salvi, Ingemar S. J. Merkies, Maryam Ferdousi, Rayaz A. Malik, Dan Ziegler, Kasper W. J. Derks, Gidon Boenhof, Filippo Martinelli-Boneschi, Daniele Cazzato, Raffaella Lombardi, Sulayman Dib-Hajj, Stephen G. Waxman, Hubert J. M. Smeets, Monique M. Gerrits, Catharina G. Faber, Giuseppe Lauria, and on behalf of the PROPANE Study Group on behalf of the PROPANE Study
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diabetic neuropathy ,small fiber neuropathy ,neuropathic pain ,molecular inversion probes ,next generation sequencing ,sodium channel genes variants - Abstract
Neuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium channel genes (SCG) expressed in a nociceptive pathway in painful and painless DPN and painful and painless SFN patients, and to provide a perspective for clinicians who assess patients with painful peripheral neuropathy. Between June 2014 and September 2016, 1125 patients with painful-DPN (n = 237), painless-DPN (n = 309), painful-SFN (n = 547) and painless-SFN (n = 32), recruited in four different centers, were analyzed for SCN3A, SCN7A-SCN11A and SCN1B-SCN4B variants by single molecule Molecular inversion probes-Next Generation Sequence. Patients were grouped based on phenotype and the presence of SCG variants. Screening of SCN3A, SCN7A-SCN11A, and SCN1B-SCN4B revealed 125 different (potential) pathogenic variants in 194 patients (17.2%, n = 194/1125). A potential pathogenic variant was present in 18.1% (n = 142/784) of painful neuropathy patients vs. 15.2% (n = 52/341) of painless neuropathy patients (17.3% (n = 41/237) for painful-DPN patients, 14.9% (n = 46/309) for painless-DPN patients, 18.5% (n = 101/547) for painful-SFN patients, and 18.8% (n = 6/32) for painless-SFN patients). Of the variants detected, 70% were in SCN7A, SCN9A, SCN10A and SCN11A. The frequency of SCN9A and SCN11A variants was the highest in painful-SFN patients, SCN7A variants in painful-DPN patients, and SCN10A variants in painless-DPN patients. Our findings suggest that rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification should aid in a better understanding of the genetic variability in patients with painful and painless neuropathy, and may lead to better risk stratification and the development of more targeted and personalized pain treatments.
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- 2023
- Full Text
- View/download PDF
7. Combined RNA interference and gene replacement therapy targeting MFN2 for the treatment of Charcot-Marie-Tooth type 2A
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Federica Rizzo, Silvia Bono, Marc David Ruepp, Sabrina Salani, Linda Ottoboni, Elena Abati, Valentina Melzi, Chiara Cordiglieri, Serena Pagliarani, Roberta De Gioia, Alessia Anastasia, Michela Taiana, Manuela Garbellini, Simona Lodato, Paolo Kunderfranco, Daniele Cazzato, Daniele Cartelli, Caterina Lonati, Nereo Bresolin, Giacomo Comi, Monica Nizzardo, and S Corti
- Abstract
Mitofusin-2 (MFN2) is an outer mitochondrial membrane protein essential for mitochondrial networking in most cells. Autosomal dominant mutations in the MFN2 gene cause Charcot-Marie-Tooth type 2A disease (CMT2A), a severe and disabling sensory-motor neuropathy that impacts the entire nervous system. Here, we propose a novel therapeutic strategy tailored to correcting the root genetic defect of CMT2A. Though mutant and wild-type MFN2 mRNA are inhibited by RNA interference (RNAi), the wild-type protein is restored by overexpressing cDNA encoding functional MFN2 modified to be resistant to RNAi. We tested this strategy in CMT2A patient-specific human induced pluripotent stem cell (iPSC)-differentiated motor neurons (MNs), demonstrating the correct silencing of endogenous MFN2 and replacement with an exogenous copy of the functional wild-type gene. This approach significantly rescues the CMT2A MN phenotype in vitro, stabilizing the altered axonal mitochondrial distribution and correcting abnormal mitophagic processes. The MFN2molecular correction was also properly confirmed in vivo in the MitoCharc1 CMT2A transgenic mouse model after cerebrospinal fluid (CSF) delivery of the constructs into newborn mice using adeno-associated virus 9 (AAV9). Altogether, our data support the feasibility of a combined RNAi and gene therapy strategy for treating the broad spectrum of human diseases associated with MFN2mutations.
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- 2023
8. TRPA1 rare variants in chronic neuropathic and nociplastic pain patients
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Margherita Marchi, Erika Salvi, Mirna Andelic, Elkadia Mehmeti, Ilaria D'Amato, Daniele Cazzato, Federica Chiappori, Raffaella Lombardi, Daniele Cartelli, Grazia Devigili, Eleonora Dalla Bella, Monique Gerrits, Rowida Almomani, Rayaz A. Malik, Milena Ślęczkowska, Anna Mazzeo, Luca Gentile, Sulayman Dib-Hajj, Stephen G. Waxman, Catharina G. Faber, Eleonora Vecchio, Marina de Tommaso, and Giuseppe Lauria
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Anesthesiology and Pain Medicine ,Neurology ,Neurology (clinical) - Published
- 2023
9. Integrative miRNA-mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy
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Mirna Andelic, Erika Salvi, Stefania Marcuzzo, Margherita Marchi, Raffaella Lombardi, Daniele Cartelli, Daniele Cazzato, Elkadia Mehmeti, Andrea Gelemanovic, Matilde Paolini, Carlotta Pardo, Ilaria D’Amato, Janneke G J Hoeijmakers, Sulayman Dib-Hajj, Stephen G Waxman, Catharina G Faber, Giuseppe Lauria, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Klinische Neurowetenschappen, and MUMC+: MA Med Staf Spec Neurologie (9)
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neuropathic pain ,EXPRESSION ,SCN9A ,small fibre neuropathy ,MICRORNA ,KERATINOCYTES ,UBIQUITIN LIGASE NEDD4-2 ,DIAGNOSIS ,CHANNEL ,CELLS ,SENSORY NEURONS ,RAT ,Neurology (clinical) ,SENSITIVITY ,skin biopsy ,miRNA - Abstract
Personalized management of neuropathic pain is an unmet clinical need due to heterogeneity of the underlying aetiologies, incompletely understood pathophysiological mechanisms and limited efficacy of existing treatments. Recent studies on microRNA in pain preclinical models have begun to yield insights into pain-related mechanisms, identifying nociception-related species differences and pinpointing potential drug candidates. With the aim of bridging the translational gap towards the clinic, we generated a human pain-related integrative miRNA and mRNA molecular profile of the epidermis, the tissue hosting small nerve fibres, in a deeply phenotyped cohort of patients with sodium channel-related painful neuropathy not responding to currently available therapies. We identified four miRNAs strongly discriminating patients from healthy individuals, confirming their effect on differentially expressed gene targets driving peripheral sensory transduction, transmission, modulation and post-transcriptional modifications, with strong effects on gene targets including NEDD4. We identified a complex epidermal miRNA-mRNA network based on tissue-specific experimental data suggesting a cross-talk between epidermal cells and axons in neuropathy pain. Using immunofluorescence assay and confocal microscopy, we observed that Nav1.7 signal intensity in keratinocytes strongly inversely correlated with NEDD4 expression that was downregulated by miR-30 family, suggesting post-transcriptional fine tuning of pain-related protein expression. Our targeted molecular profiling advances the understanding of specific neuropathic pain fine signatures and may accelerate process towards personalized medicine in patients with neuropathic pain.Andelic et al. identify miRNA-driven epidermal regulatory mechanisms in SCN9A-related painful neuropathy not responding to currently available therapies. By revealing unique molecular signatures of neuropathic pain in deeply phenotyped patients, these findings could accelerate the development of personalized therapies.
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- 2023
10. N°369 – Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: Reassessment of rules
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Paola Lanteri, Mikael Gian Andrea Izzo, Grazia Devigili, Davide Rossi Sebastiano, Daniele Cazzato, Ramona Togni, Valentina Catanzaro, Ylenia Melillo, Roberto Eleopra, and Francesco Dimeco
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Neurology ,Physiology (medical) ,Neurology (clinical) ,Sensory Systems - Published
- 2023
11. Significance and clinical suggestions for the Somatosensory Evoked Potentials increased in amplitude revealed by a large sample of neurological patients
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Davide Rossi Sebastiano, Daniele Cazzato, Elisa Visani, Eleonora Dalla Bella, Laura Brambilla, Grazia Devigili, Paola Caroppo, Lorenzo Maggi, Lorenzo Nanetti, Ettore Salsano, Laura Canafoglia, Isabella Canavero, Elena Anghileri, Deborah Bonfoco, and Paola Lanteri
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Myoclonus ,Psychiatry and Mental health ,Epilepsy ,Evoked Potentials, Somatosensory ,Humans ,Electroencephalography ,Epilepsies, Myoclonic ,Neurology (clinical) ,Dermatology ,General Medicine ,Somatosensory Cortex ,Median Nerve - Abstract
ObjectivesTo investigate the relationship between N20-P25 peak-to-peak amplitude (N20p-P25p) of Somatosensory Evoked Potentials (SEPs) and the occurrence of abnormalities of the peripheral and/or central sensory pathways and of myoclonus/epilepsy, in 308 patients with increased SEPs amplitude from upper limbs stimulationMethodsWe compared cortical response (N20p-P25p) in different groups of patients identified by demographic, clinical and neurophysiological factors and performed a cluster analysis for classifying the natural occurrence of subgroups of patients.ResultsNo significant differences of N20p-P25p were found among different age-dependent groups, and in patients with or without PNS/CNS abnormalities of sensory pathways, while myoclonic/epileptic patients showed higher N20p-P25p than other groups. Cluster analysis identified four clusters including patients with myoclonus/epilepsy, patients with central sensory abnormalities, patients with peripheral sensory abnormalities, patients with neither myoclonus nor sensory abnormalities.ConclusionsIncreased N20p-P25p correlated to different pathophysiological conditions: strong cortical hyperexcitability in patients with cortical myoclonus and/or epilepsy and enlarged N20p-P25p, while milder increase of N20p-P25p could be underpinned by plastic cortical changes following abnormalities of sensory pathways, or degenerative process involving the cortex. SEPs increased in amplitude cannot be considered a specific correlated for myoclonus/epilepsy, but it in several neurological disorders may represent a sign of adaptive, plastic and/or degenerative cortical changes.
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- 2022
12. Clinical diagnosis and management of small fiber neuropathy: an update on best practice
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Grazia Devigili, Giuseppe Lauria, and Daniele Cazzato
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medicine.medical_specialty ,Heterogeneous group ,medicine.diagnostic_test ,business.industry ,Small Fiber Neuropathy ,General Neuroscience ,Quantitative sensory testing ,Autonomic disorder ,030227 psychiatry ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Clinical diagnosis ,Skin biopsy ,Neuropathic pain ,medicine ,Humans ,Pharmacology (medical) ,Neurology (clinical) ,Autonomic disturbances ,business ,030217 neurology & neurosurgery - Abstract
Small fiber neuropathy (SFN) is a heterogeneous group of disorders affecting thin myelinated Aδ and unmyelinated C fibers. Common symptoms include neuropathic pain and autonomic disturbances, and the typical clinical presentation is that of a length-dependent polyneuropathy, although other distributions could be present.This review focuses on several aspects of SFN including etiology, clinical presentation, diagnostic criteria and tests, management, and future perspectives. Diagnostic challenges are discussed, encompassing the role of accurate and standardized assessment of symptoms and signs and providing clues for the clinical practice. The authors discuss the evidence in support of skin biopsy and quantitative sensory testing as diagnostic tests and present an overview of other diagnostic techniques to assess sensory and autonomic fibers dysfunction. The authors also suggest a systematic approach to the etiology including a set of laboratory tests and genetic examinations of sodium channelopathies and other rare conditions that might drive the therapeutic approach based on underlying cause or symptoms treatment.SFN provides a useful model for neuropathic pain whose known mechanisms and cause could pave the way toward personalized treatments.
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- 2020
13. Diagnostic criteria for small fibre neuropathy in clinical practice and research
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Daniele Cazzato, Erika Salvi, Giuseppe Lauria, Margherita Marchi, Grazia Devigili, Sara Rinaldo, Raffaella Lombardi, and Roberto Eleopra
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Small Fiber Neuropathy ,Neural Conduction ,quantitative sensory testing ,Young Adult ,03 medical and health sciences ,Nerve Fibers ,0302 clinical medicine ,Humans ,Medicine ,skin biopsy ,Aged ,Retrospective Studies ,Skin ,neuropathic pain ,medicine.diagnostic_test ,small fibre neuropathy ,business.industry ,Electrodiagnosis ,Quantitative sensory testing ,Clinical study design ,Original Articles ,Middle Aged ,Dermatology ,body regions ,Clinical Practice ,Clinical trial ,030104 developmental biology ,Sensory Thresholds ,diagnostic criteria ,Neuropathic pain ,Skin biopsy ,Small Fibre Neuropathy ,Sensory neuropathy ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Definitive diagnostic criteria for small fibre neuropathy have yet to be established, with implications both for clinical practice and for the design of clinical trials. Devigili et al. demonstrate that a combined approach – with clinical, functional and structural assessment of small nerve fibres – improves the reliability of diagnosis., The diagnostic criteria for small fibre neuropathy are not established, influencing the approach to patients in clinical practice, their access to disease-modifying and symptomatic treatments, the use of healthcare resources, and the design of clinical trials. To address these issues, we performed a reappraisal study of 150 patients with sensory neuropathy and a prospective and follow-up validation study of 352 new subjects with suspected sensory neuropathy. Small fibre neuropathy diagnostic criteria were based on deep clinical phenotyping, quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD). Small fibre neuropathy was ruled out in 5 of 150 patients (3.3%) of the reappraisal study. Small fibre neuropathy was diagnosed at baseline of the validation study in 149 of 352 patients (42.4%) based on the combination between two clinical signs and abnormal QST and IENFD (69.1%), abnormal QST alone (5.4%), or abnormal IENFD alone (20.1%). Eight patients (5.4%) had abnormal QST and IENFD but no clinical signs. Further, 38 patients complained of sensory symptoms but showed no clinical signs. Of those, 34 (89.4%) had normal QST and IENFD, 4 (10.5%) had abnormal QST and normal IENFD, and none had abnormal IENFD alone. At 18-month follow-up, 19 of them (56%) reported the complete recovery of symptoms and showed normal clinical, QST and IENFD findings. None of those with one single abnormal test (QST or IENFD) developed clinical signs or showed abnormal findings on the other test. Conversely, all eight patients with abnormal QST and IENFD at baseline developed clinical signs at follow-up. The combination of clinical signs and abnormal QST and/or IENFD findings can more reliably lead to the diagnosis of small fibre neuropathy than the combination of abnormal QST and IENFD findings in the absence of clinical signs. Sensory symptoms alone should not be considered a reliable screening feature. Our findings demonstrate that the combined clinical, functional and structural approach to the diagnosis of small fibre neuropathy is reliable and relevant both for clinical practice and clinical trial design.
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- 2019
14. Headache, chest pain, and multiplex cranial neuropathy
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Giuseppe Lauria Pinter, Franco Ferracci, Susanna Usai, Daniele Cazzato, Alessandro Perin, Alessandra Erbetta, and Gianluca Marucci
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medicine.medical_specialty ,Neurology ,business.industry ,Dermatology ,General Medicine ,Cranial neuropathy ,Chest pain ,Psychiatry and Mental health ,medicine ,Multiplex ,Neurology (clinical) ,Radiology ,Neurosurgery ,medicine.symptom ,business ,Neuroradiology - Published
- 2019
15. Syncope at SARS-CoV-2 onset
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Ciro Canetta, Giuseppe Emanuele La Piana, Roberto Assandri, Chiara Benzoni, Gianfranco Gaudiano, Silvia Accordino, Susanna Usai, Giovanni Viganò, Davide Sebastiano Rossi, Alberto Astengo, Gianpaolo Benelli, Giuseppe Lauria, Daniele Cazzato, Alessandro Scartabellati, Irene Tramacere, and Elisabetta Buscarini
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Tachycardia ,Adult ,Male ,medicine.medical_specialty ,Chemoreceptor ,Short Communication ,Angiotensin-converting enzyme-2 (ACE2) receptor ,Clinical Neurology ,Baroreflex ,Baroreceptor reflex ,pCO2 ,Syncope ,Hypoxemia ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Heart Rate ,Internal medicine ,Heart rate ,Medicine ,Humans ,Hypoxia ,Hypocapnic hypoxemia ,Aged ,Aged, 80 and over ,biology ,Hypocapnia ,business.industry ,SARS-CoV-2 ,Endocrine and Autonomic Systems ,Solitary tract ,Syncope (genus) ,COVID-19 ,Middle Aged ,biology.organism_classification ,respiratory tract diseases ,Central chemoreceptors ,Cardiology ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,circulatory and respiratory physiology - Abstract
We describe clinical and laboratory findings in 35 patients tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction on nasopharyngeal swab experiencing one or multiple syncope at disease onset. Clinical neurologic and cardiologic examination, and electrocardiographic findings were normal. Chest computed tomography showed findings consistent with interstitial pneumonia. Arterial blood gas analysis showed low pO2, pCO2, and ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) indicating hypocapnic hypoxemia. Patients who presented with syncope showed significantly lower heart rate as compared to 68 SARS-CoV-2 positive that did not. Such poorer than expected compensatory heart rate increase may have led to syncope based on individual susceptibility. We speculate that SARS-CoV-2 could have caused angiotensin-converting enzyme-2 (ACE2) receptor internalization in the nucleus of the solitary tract and other midbrain nuclei, impairing baroreflex and chemoreceptor response, and inhibiting the compensatory tachycardia during acute hypocapnic hypoxemia.
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- 2020
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16. Life with chronic pain during COVID-19 lockdown: the case of patients with small fibre neuropathy and chronic migraine
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Daniele Cazzato, Licia Grazzi, Giuseppe Lauria, Alessandra Telesca, and Monica Consonni
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Quality of life ,Adult ,Male ,medicine.medical_specialty ,Migraine Disorders ,Small Fiber Neuropathy ,Clinical Neurology ,Chronic pain ,Dermatology ,COVID-19 distress ,Psychological Distress ,03 medical and health sciences ,0302 clinical medicine ,Chronic Migraine ,medicine ,Humans ,Family ,030212 general & internal medicine ,Chronic migraine ,Small fibre neuropathy ,Aged ,business.industry ,Catastrophization ,Catastrophism ,COVID-19 ,Loneliness ,General Medicine ,Middle Aged ,medicine.disease ,Mental health ,Distress ,Psychiatry and Mental health ,Mood ,Italy ,Communicable Disease Control ,Physical therapy ,Anxiety ,Neuralgia ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveWe aimed at investigating the impact of COVID-19-related distress on patients with chronic pain, highlighting the effects of changes in individual habits and public health care reconfiguration on physical and psychological health.MethodsDuring the pandemic, 80 participants (25 patients with small fibre neuropathy (SFN), 42 patients with chronic migraine (CM) and 13 patients’ healthy family members (HFM)) were asked to evaluate their COVID-19 complains, changes in habits and clinical management, behaviour, mood, loneliness, quality of life (QoL), physical and mental health and coping strategies. Data were analysed by Spearman rho correlations and Mann-WhitneyUtests.ResultsPatients had lower QoL, lower physical health and higher catastrophizing attitude towards pain than HFM. During the pandemic, SFN patients referred greater decline in clinical symptoms, worries about contagion and discomfort for disease management changes than CM patients. In the SFN group, the higher levels of disability were associated with suffering from changes in neurologist-patient relationship. CM patients complained of agitation/anxiety that was related to feelings of loneliness, depressive mood and catastrophism.DiscussionDespite similar complains of change in habits and worries about COVID-19 pandemic, SFN and CM patients had distinct reactions. In SFN patients, pandemic distress impacted on physical health with worsening of clinical conditions, especially suffering from changes in their care. In CM patients, pandemic distress affected behaviour, mainly with psychological frailty. This suggests the need to customize public health care for patients with distinct chronic pain conditions.
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- 2020
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17. Placebo effect in chronic inflammatory demyelinating polyneuropathy: The PATH study and a systematic review
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Martin Stangel, K. George, Inna Rubanovits, A. Kutschenko, Michael Schroeter, Juliane Klehmet, Tsugio Akutsu, Robert D. Henderson, S. Mumfrey, Takuya Ohkubo, Helmar C. Lehmann, Mari Auranen, Paul Bassett, Giuseppe Lauria, A. Di Muzio, Kenichi Kaida, David Yarnitsky, S. Larue, R. Gold, Fabian Klostermann, Karissa L. Gable, Ivo N. van Schaik, Gens Sobue, A Schenone, U. Sorro, Jeffrey A. Allen, S. Attarian, A. Algom, U. Chyrchel-Paszkiewicz, J. Haas, Jens Ejbye Schmidt, I. N. van Schaik, Jasper M. Morrow, Ingemar S. J. Merkies, R. Carne, C. Marquez Infante, Michael P. Lunn, Khema Sharma, E. Chi Ho Lai, Billie L. Durn, Satoshi Kuwabara, D. Kramer, David Gosal, P. MacDonald, Janneke G. J. Hoeijmakers, Giovanni Antonini, Senda Ajroud-Driss, S. Muley, Takanori Yokota, Tim Hagenacker, Eroboghene E. Ubogu, M. Kawai, Maria Salvado, Jean Pouget, Mika Saarela, John T. Kissel, Alexander Shtilbans, K. Kanai, B. Murinson, Olaf Hoffmann, Claudia Sommer, Sandro Sorbi, P. Berlit, Norman Latov, Nora A. Visser, C. G. Faber, A. Wielanek, J. Demeestere, Ericka Simpson, Ginna Gonzalez, Konrad Rejdak, C. Casanovas Pons, Alessandro Testori, Orell Mielke, T. Kalous, Alexa Cleasby, Vera Bril, J. Sussova, D. Mueller, Katrin Gross-Paju, Dale J. Lange, Nicolette C. Notermans, Florian Then Bergh, R. Talab, Kazumasa Yokoyama, M. Zibetti, C. Trebst, Marina Grandis, Miriam Freimer, E. Delmon, David R. Cornblath, Masahiro Mori, H. Onoue, Richard J. Barohn, D. Liebetanz, M. Chatzopoulos, J. Oechtering, F. Ciccocioppo, T. Rao, P. Van Damme, A. Sabet, Takashi Kanda, J. Zschuentzsch, Hans-Peter Hartung, S. Benitez, D. Aufauvre, M. Bednar, M. Tomiyama, G. Le Masson, C. D'Amour, Richard A. Lewis, Anne D. Sperfeld, I. Melamed, Lisa D. Hobson-Webb, Stefan Blum, Dario Cocito, K. Nishiyama, Daniele Cazzato, F. Bethke, Toomas Toomsoo, Said R. Beydoun, Leslie Roberts, David Walk, Josep Gamez, Masahiro Iijima, A. Jaspert-Grehl, Israel V. Drory, P. Kunc, John-Philip Lawo, C. Goerlitz, H. Johl, R. Yoon, Daniela M. Menichella, T. Lavin, Stefania Morino, K. Ohyama, Masayuki Baba, M. Antonia, Shafeeq Ladha, Claude Desnuelle, Pierre Clavelou, Andreas Meisel, Martin Vališ, Filip Eftimov, P. Baum, Sabrina Matà, Russell L. Chin, Mazen M. Dimachkie, ANS - Neuroinfection & -inflammation, Neurology, and AII - Inflammatory diseases
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Research design ,CIDP ,immunoglobulin ,non-relapse ,placebo ,relapse ,Humans ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,Immunologic Factors ,Outcome Assessment, Health Care ,Placebo Effect ,Randomized Controlled Trials as Topic ,Research Design ,Research Report ,medicine.medical_specialty ,Outcome Assessment ,SUBCUTANEOUS IMMUNOGLOBULIN ,Polyradiculoneuropathy ,non‐relapse ,Severe disease ,PLASMA-EXCHANGE ,Chronic inflammatory demyelinating polyneuropathy ,Placebo ,THERAPY ,Immunoglobulin G ,03 medical and health sciences ,DOUBLE-BLIND ,0302 clinical medicine ,Internal medicine ,Clinical endpoint ,Medicine ,Chronic Inflammatory Demyelinating ,biology ,business.industry ,General Neuroscience ,INTRAVENOUS IMMUNOGLOBULIN TREATMENT ,Research Reports ,medicine.disease ,Health Care ,INTERFERON BETA-1A ,030220 oncology & carcinogenesis ,biology.protein ,TRIAL ,Neurology (clinical) ,business ,Polyneuropathy ,030217 neurology & neurosurgery - Abstract
The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post‐hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo‐controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non‐deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration.
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- 2020
18. Syncope at SARS-CoV-2 onset due to impaired baroreflex response
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Irene Tramacere, Elisabetta Buscarini, Roberto Assandri, Alessandro Scartabellati, Daniele Cazzato, Giovanni Viganò, Ciro Canetta, Davide Rossi, Alberto Astengo, Giuseppe Lauria, Chiara Benzoni, La Piana G, Accordino S, Gaudiano G, Susanna Usai, and Gianpaolo Benelli
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Tachycardia ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Solitary tract ,Neurological examination ,Baroreflex ,pCO2 ,respiratory tract diseases ,Hypoxemia ,Electrocardiographic Finding ,Internal medicine ,Heart rate ,medicine ,Cardiology ,medicine.symptom ,business ,circulatory and respiratory physiology - Abstract
We describe clinical and laboratory findings in 35 consecutive patients tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction on nasopharyngeal swab that presented one or multiple syncopal events at disease onset. Neurological examination and electrocardiographic findings were normal. Chest computed tomography showed findings consistent with interstitial pneumonia. Arterial blood gas analysis showed low pO2, pCO2, and P/F ratio indicating hypocapnic hypoxemia, while patients did not show the expected compensatory heart rate increase. Such mechanism could have led to syncope. We speculate that SARS-CoV-2 could have caused angiotensin-converting enzyme-2 (ACE2) receptor internalization in the nucleus of the solitary tract (NTS), thus altering the baroreflex response and inhibiting the compensatory tachycardia during acute hypocapnic hypoxemia.
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- 2020
19. Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients
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Roberto Assandri, Elena Iiritano, Roberto Sfogliarini, Samanta Romeo, Giuseppe Lapiana, Gianfranco Brambilla, Elisabetta Buscarini, Giovanni Melilli, Irene Tramacere, Claudio Londoni, Davide Rossi, Daniele Cazzato, Saverio Alicante, Ciro Canetta, Susanna Usai, Alessandro Scartabellati, Gianpaolo Benelli, Germano Pellegata, Guido Manfredi, Fernanda Menozzi, Guido Merli, Giuseppe Lauria, Giovanni Viganò, and Marianna Pedaci
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Abdominal pain ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,medicine.diagnostic_test ,business.industry ,Nausea ,Emergency department ,Intensive care unit ,law.invention ,Diarrhea ,Pulse oximetry ,law ,Internal medicine ,medicine ,Medical history ,medicine.symptom ,business - Abstract
ObjectiveTo assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients.DesignSince February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. were recorded.ResultsGI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-… days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms.ConclusionsGI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.
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- 2020
20. SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy
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Germano Pellegata, Ciro Canetta, Alessandro Scartabellati, Davide Sebastiano Rossi, Giuseppe Emanuele La Piana, Gianpaolo Benelli, Susanna Usai, Daniele Cazzato, Elisabetta Buscarini, Giuseppe Lauria, Roberto Assandri, Giovanni Melilli, Guido Merli, Irene Tramacere, Roberto Sfogliarini, Giovanni Viganò, Guido Caldarelli, and Tommaso Gili
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Male ,Pulmonology ,Angiotensin-Converting Enzyme Inhibitors ,Comorbidity ,Biochemistry ,Diagnostic Radiology ,0302 clinical medicine ,Endocrinology ,Medical Conditions ,dipeptidyl carboxypeptidase inhibitor ,Case fatality rate ,Young adult ,Child ,Tomography ,Aged, 80 and over ,C-Reactive Proteins ,Icu admission ,Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici ,3. Good health ,C-Reactive Protein ,Blood ,Italy ,Child, Preschool ,Population study ,Medicine ,SARS CoV 2 ,Network Analysis ,medicine.medical_specialty ,Imaging Techniques ,Endocrine Disorders ,Science ,Microbiology ,03 medical and health sciences ,Diabetes Mellitus ,Humans ,Aged ,Medicine and health sciences ,Gold standard ,C-reactive protein ,Organisms ,Proteins ,Pneumonia ,medicine.disease ,Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin) ,Computed Axial Tomography ,Population Groupings ,Neuroscience ,RNA viruses ,Hospitalized patients ,Coronaviruses ,Physiology ,030204 cardiovascular system & hematology ,Risk Factors ,030212 general & internal medicine ,Prospective cohort study ,Pathology and laboratory medicine ,C reactive protein ,Multidisciplinary ,biology ,Radiology and Imaging ,Middle Aged ,Medical microbiology ,Body Fluids ,Hospitalization ,Treatment Outcome ,Viruses ,sartan derivative ,Female ,Pathogens ,Anatomy ,Research Article ,Adult ,Computer and Information Sciences ,Adolescent ,SARS coronavirus ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Neuroimaging ,Research and Analysis Methods ,Young Adult ,Diagnostic Medicine ,Diabetes mellitus ,Internal medicine ,medicine ,Biology and life sciences ,business.industry ,SARS-CoV-2 ,Viral pathogens ,COVID-19 ,Angiotensin-converting enzyme ,COVID-19 Drug Treatment ,Microbial pathogens ,Blood Counts ,Age Groups ,Metabolic Disorders ,People and Places ,biology.protein ,business - Abstract
No systematic data on hospitalized SARS-COV-2 patients from Western countries are available. We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (66.6% males) median age was 70.5 years (range 1-99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60-69 years old, 21.1% in 70-79 years old, 38.8% in 80-89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Older age, cough and dyspnea at onset, hypertension, cardiovascular diseases, diabetes, renal insufficiency, >7 drugs intake and positive X-ray, low lymphocyte count, high C-reactive protein, aspartate aminotransferase and lactate dehydrogenase values, and low PO2 partial pressure with high lactate at arterial blood gas analysis at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Comorbidity network analysis revealed homogenous distribution of deceased and 60-80 aged SARS-COV-2 patients across diseases. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1-98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% sensitivity. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre- existing multiorgan impairment. ACE inhibitors and sartans did not influence patients’ outcome.
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- 2020
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21. Laser capture microdissection for transcriptomic profiles in human skin biopsies
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Filippo Martinelli Boneschi, Raffaella Lombardi, Margherita Marchi, Silvia Peroni, Giancarlo Comi, Ignazio Diego Lopez, Ferdinando Clarelli, Silvia Santoro, Andrea Zauli, Ana Maria Osiceanu, Daniele Cazzato, Angelo Quattrini, Melissa Sorosina, Raffaele A. Calogero, and Giuseppe Lauria
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0301 basic medicine ,Male ,lcsh:QH426-470 ,RNase P ,Biopsy ,Human skin ,Computational biology ,Biology ,Transcriptome ,03 medical and health sciences ,Idiopathic neuropathy ,medicine ,Skin biopsy ,Humans ,lcsh:QH573-671 ,Transcriptomics ,Molecular Biology ,Laser capture microdissection ,Aged ,Skin ,medicine.diagnostic_test ,Sequence Analysis, RNA ,lcsh:Cytology ,Methodology Article ,Gene Expression Profiling ,RNA ,High-Throughput Nucleotide Sequencing ,RNA sequencing ,Middle Aged ,Gene expression profiling ,lcsh:Genetics ,030104 developmental biology ,MRNA Sequencing ,Female - Abstract
Background The acquisition of reliable tissue-specific RNA sequencing data from human skin biopsy represents a major advance in research. However, the complexity of the process of isolation of specific layers from fresh-frozen human specimen by laser capture microdissection, the abundant presence of skin nucleases and RNA instability remain relevant methodological challenges. We developed and optimized a protocol to extract RNA from layers of human skin biopsies and to provide satisfactory quality and amount of mRNA sequencing data. Results The protocol includes steps of collection, embedding, freezing, histological coloration and relative optimization to preserve RNA extracted from specific components of fresh-frozen human skin biopsy of 14 subjects. Optimization of the protocol includes a preservation step in RNALater® Solution, the control of specimen temperature, the use of RNase Inhibitors and the time reduction of the staining procedure. The quality of extracted RNA was measured using the percentage of fragments longer than 200 nucleotides (DV200), a more suitable measurement for successful library preparation than the RNA Integrity Number (RIN). RNA was then enriched using the TruSeq® RNA Access Library Prep Kit (Illumina®) and sequenced on HiSeq® 2500 platform (Illumina®). Quality control on RNA sequencing data was adequate to get reliable data for downstream analysis. Conclusions The described implemented and optimized protocol can be used for generating transcriptomics data on skin tissues, and it is potentially applicable to other tissues. It can be extended to multicenter studies, due to the introduction of an initial step of preservation of the specimen that allowed the shipment of biological samples. Electronic supplementary material The online version of this article (10.1186/s12867-018-0108-5) contains supplementary material, which is available to authorized users.
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- 2018
22. Ricolinostat induces microtubule acetylation and neurite regeneration in cellular models of diabetic and chemotheraphy-induced neuropathy
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Mirna Andelic, Margherita Marchi, Daniele Cartelli, Giuseppe Lauria, Erika Salvi, Daniele Cazzato, Samanta Mazzetti, Graziella Cappelletti, Raffaella Lombardi, and Ilaria D'Amato
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Neurology ,Microtubule ,Chemistry ,Acetylation ,Ricolinostat ,Neurology (clinical) ,Neurite regeneration ,Cell biology - Published
- 2021
23. Genetic study of Italian families affected by small fibre neuropathy identified variants in predisposing pain phenotype
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Massimo Filippi, Filippo Martinelli Boneschi, Kaalindi Misra, Federica Esposito, Giuseppe Lauria, Silvia Santoro, Margherita Marchi, Erika Salvi, Raffaella Lombardi, Andrea Zauli, and Daniele Cazzato
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Genetics ,Neurology ,business.industry ,Small Fibre Neuropathy ,Medicine ,Neurology (clinical) ,business ,Phenotype - Published
- 2021
24. Small fibre neuropathy
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Daniele Cazzato and Giuseppe Lauria
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Neurologic Examination ,0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Biopsy ,Small Fiber Neuropathy ,Humans ,Neuralgia ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
To provide a review on the state-of-art of clinical features, diagnostics, genetics and treatments of small fibre neuropathy (SFN).The spectrum of clinical features has been widened from the classical presentation of burning feet as length-dependent SFN to that of small fibre dysfunction and/or degeneration associated with focal, diffuse and episodic neuropathic pain syndromes. The involvement of small nerve fibres in neurodegenerative diseases has been further defined, challenging the relationship between neuropathic pain symptoms and small fibre loss. The clinical reliability of skin biopsy has been strengthened by the availability of normative values for both the immunohistochemistry techniques used and their comparison, and by side and short-term follow-up analyses. Corneal confocal microscopy has implemented its diagnostic potentiality because of the availability of age-adjusted and sex-adjusted normative values. Genetic studies expanded the panel on genes involved in SFN because of the discovery of new mutations in SCN10A and SCN11A, besides the first found in SCN9A, and identification of mutations in COL6A5 in patients with itching.In the last 5 years, the chapter of SFN has been widened by new clinical and genetics descriptions leading to a more comprehensive approach to patients in clinical practice and research.
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- 2017
25. GI symptoms as early signs of COVID-19 in hospitalised Italian patients
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E. Iiritano, Alessandro Scartabellati, Germano Pellegata, Fernanda Menozzi, Samanta Romeo, Roberto Sfogliarini, Giuseppe Emanuele La Piana, Marianna Pedaci, Daniele Cazzato, Saverio Alicante, Ciro Canetta, Giampaolo Benelli, Roberto Assandri, Davide Sebastiano Rossi, Susanna Usai, Giovanni Melilli, Irene Tramacere, Claudio Londoni, Guido Manfredi, Giuseppe Lauria, Giovanni Viganò, G. Brambilla, Guido Merli, and Elisabetta Buscarini
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0301 basic medicine ,medicine.medical_specialty ,Abdominal pain ,Gi symptoms ,Coronavirus disease 2019 (COVID-19) ,Nausea ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,gastrointestinal pathology ,clinical decision making ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Medical history ,Pandemics ,SARS-CoV-2 ,business.industry ,abdominal pain ,Gastroenterology ,COVID-19 ,gastric diseases ,PostScript ,diarrhoea ,030104 developmental biology ,Italy ,Radiological weapon ,Vomiting ,030211 gastroenterology & hepatology ,gastrointestinal tract ,medicine.symptom ,Coronavirus Infections ,business - Abstract
Objective To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. Design We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. Results Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. Conclusions GI tract may be a potential transmission route and target organ of SARS-CoV-2.
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- 2020
26. Trigeminal Neuralgia: Channels, Pathophysiology, and Therapeutic Challenges
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Giuseppe Lauria, Lars Bendtsen, Daniele Cazzato, and Stine Maarbjerg
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Trigeminal nerve ,business.industry ,Carbamazepine ,medicine.disease ,Pathophysiology ,Excruciating ,Therapeutic approach ,Trigeminal neuralgia ,Neuropathic pain ,medicine ,Severe pain ,business ,Neuroscience ,medicine.drug - Abstract
Trigeminal neuralgia (TN) is a condition characterized by paroxysmal excruciating and usually unilateral pain attacks within the territory of one or more divisions of the trigeminal nerve. The underlying pathophysiological mechanisms remain poorly understood. The abrupt onset and termination of electric shock-like severe pain, the triggering role of non-noxious light sensory stimuli, the spreading of pain beyond the stimulated area, and the post-attack refractoriness represent some of the intriguing and challenging aspects of TN pathophysiology. This chapter reviews the updated pathophysiological hypotheses for TN, the emerging role of ion channels potentially representing novel therapeutic targets for the treatment of the disorder, and the current therapeutic approach based on a diagnostic work-up and treatment algorithm.
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- 2019
27. Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study
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Michael Schroeter, Amgad Shebl, Leslie Roberts, Takuya Ohkubo, M. Chatzopoulos, Nan van Geloven, Robert D. Henderson, Catharina G. Faber, R. Talab, K. George, A. Kutschenko, E. Chi-Ho Lai, M. Bednar, Inna Rubanovits, Claudia Sommer, J. Oechtering, M. Tomiyama, Hans-Peter Hartung, Mari Auranen, G. Le Masson, Konrad Rejdak, Marina Grandis, Eroboghene E. Ubogu, Senda Ajroud-Driss, Tim Hagenacker, Lisa D. Hobson-Webb, Masayuki Baba, Khema Sharma, Miriam Freimer, Kazumasa Yokoyama, U. Chyrchel-Paszkiewicz, Karissa L. Gable, P. Van Damme, J. Zschuentzsch, I. N. van Schaik, S. Benitez, K. Nishiyama, J. Demeestere, Daniele Cazzato, F. Bethke, R. Carne, Gen Sobue, C. Marquez Infante, Norman Latov, David Walk, B. Murinson, Katrin Gross-Paju, Helmar C. Lehmann, M. Antonia, Ginna Gonzalez, M. Zibetti, Anne-Cécile Wielanek-Bachelet, Vera Bril, Stefania Morino, Mika Saarela, S. Mumfrey, Said R. Beydoun, Takanori Yokota, Maria Salvado, John T. Kissel, C. D'Amour, Ericka Simpson, D. Aufauvre, P. MacDonald, Orell Mielke, David R. Cornblath, Masahiro Iijima, Janneke G. J. Hoeijmakers, Nora A. Visser, Takashi Kanda, K. Kanai, Jeffrey A. Allen, Richard A. Lewis, Anne D. Sperfeld, J. Sussova, D. Mueller, A. Algom, Fabian Klostermann, I. Melamed, David Yarnitsky, J. Haas, Josep Gamez, A Schenone, P. Kunc, Ingemar S. J. Merkies, C. Trebst, F. Ciccocioppo, Ralf Gold, Vivian E. Drory, H. Onoue, Stefan Blum, P. Berlit, S. Muley, Tsugio Akutsu, T. Kalous, Michael P. Lunn, Alessandro Testori, Dale J. Lange, Giuseppe Lauria, D. Liebetanz, A. Jaspert-Grehl, Giovanni Antonini, Masahiro Mori, S. Larue, John-Philip Lawo, C. Goerlitz, H. Johl, M. Kawai, Nicolette C. Notermans, U. Sorro, R. Yoon, Daniela M. Menichella, T. Lavin, Billie L. Durn, J. Morrow, Richard J. Barohn, Dario Cocito, T. Rao, Martin Stangel, Satoshi Kuwabara, Jean Pouget, Emilien Delmont, David Gosal, Alexander Shtilbans, Sandro Sorbi, Florian Then Bergh, J. Schmidt, Shahram Attarian, Pierre Clavelou, Andreas Meisel, Sabrina Matà, Russell L. Chin, Mazen M. Dimachkie, Juliane Klehmet, K. Ohyama, Martin Vališ, Filip Eftimov, Shafeeq Ladha, A. Sabet, P. Baum, Claude Desnuelle, Kenichi Kaida, D. Kramer, Olaf Hoffmann, C. Casanovas Pons, A. Di Muzio, Ivo N. van Schaik, Toomas Toomsoo, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, AII - Inflammatory diseases, CSL Behring, Meridian HealthComms, and Demeestere, Jelle
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Research Report ,Male ,Outcome Assessment ,inflammatory neuropathy cause and treatment (INCAT) ,chronic inflammatory demyelinating polyneuropathy (CIDP) ,intravenous immunoglobulin (IVIG) ,polyneuropathy and treatment with Hizentra (PATH) ,Privigen ,Neuroscience (all) ,Neurology (clinical) ,Medizin ,Polyneuropathy and treatment with Hizentra (PATH) ,Chronic inflammatory demyelinating polyneuropathy ,law.invention ,Chronic inflammatory demyelinating polyneuropathy (CIDP) ,0302 clinical medicine ,Randomized controlled trial ,law ,hemic and lymphatic diseases ,Outcome Assessment, Health Care ,80 and over ,Young adult ,Chronic Inflammatory Demyelinating ,Aged, 80 and over ,biology ,Intravenous immunoglobulin (IVIG) ,General Neuroscience ,Immunoglobulins, Intravenous ,Middle Aged ,3. Good health ,Methylprednisolone ,chronic inflammatory demyelinating polyneuropathy (cidp) ,inflammatory neuropathy cause and treatment (incat) ,intravenous immunoglobulin (ivig) ,polyneuropathy and treatment with hizentra (path) ,privigen ,030220 oncology & carcinogenesis ,Anesthesia ,Female ,Antibody ,Intravenous ,Polyneuropathy ,Adult ,Aged ,Follow-Up Studies ,Humans ,Immunoglobulin G ,Immunologic Factors ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,Young Adult ,medicine.drug ,Randomization ,Neuroscience(all) ,Clinical Neurology ,Polyradiculoneuropathy ,Immunoglobulins ,Inflammatory neuropathy cause and treatment (INCAT) ,03 medical and health sciences ,medicine ,Journal Article ,business.industry ,Research Reports ,medicine.disease ,Health Care ,biology.protein ,business ,030217 neurology & neurosurgery - Abstract
PATH study group., In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre‐randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow‐up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post‐study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal., Editorial support was provided by Meridian HealthComms Ltd, funded by CSL Behring.
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- 2019
28. COL6A5 variants in familial neuropathic chronic itch
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Daniele Cazzato, Stephen G. Waxman, Raffaella Lombardi, Paola Grammatico, Nicoletta Zoppi, Margherita Marchi, Sulayman D. Dib-Hajj, Roberto Eleopra, Jenny Sassone, Hassan Fadavi, Marco Ritelli, Claudio Doglioni, Catharina G. Faber, Monique M. Gerrits, Daniela Toniolo, Grazia Devigili, Ingemar S. J. Merkies, Silvia Santoro, Marina Colombi, Chiara Dordoni, Massimiliano Cocca, Marco Castori, Michela Taiana, Giuseppe Lauria, Filippo Martinelli-Boneschi, Andrea Zauli, Rowida Almomani, Rayaz A. Malik, Melissa Sorosina, Martinelli Boneschi, Filippo, Colombi, Marina, Castori, Marco, Devigili, Grazia, Eleopra, Roberto, Malik, Rayaz A, Ritelli, Marco, Zoppi, Nicoletta, Dordoni, Chiara, Sorosina, Melissa, Grammatico, Paola, Fadavi, Hassan, Gerrits, Monique M, Almomani, Rowida, Faber, Catharina G, Merkies, Ingemar S. J, Toniolo, Daniela, Cocca, Massimiliano, Doglioni, Claudio, Waxman, Stephen G, Dib Hajj, Sulayman D, Taiana, Michela M, Sassone, Jenny, Lombardi, Raffaella, Cazzato, Daniele, Zauli, Andrea, Santoro, Silvia, Marchi, Margherita, Lauria, Giuseppe, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Klinische Neurowetenschappen, Filippo, Martinelli Boneschi, Marina, Colombi, Marco, Castori, Grazia, Devigili, Roberto, Eleopra, Rayaz, Malik, Marco, Ritelli, Nicoletta, Zoppi, Chiara, Dordoni, Melissa, Sorosina, Paola, Grammatico, Hassan, Fadavi, Monique, M. Gerrit, Rowida, Almomani, Catharina, G. Faber, Ingemar, S. J. Merkie, Daniela, Toniolo, Massimiliano, Cocca, Stephen, G. Waxman, Sulayman, D. Dib Hajj, Michela, M. Taiana, SASSONE PAGANO, Jenny, Raffaella, Lombardi, Daniele, Cazzato, Andrea, Zauli, Silvia, Santoro, Margherita, Marchi, and Giuseppe, Lauria
- Subjects
0301 basic medicine ,Male ,Pathology ,Diabetic neuropathy ,SYMPTOMS ,NOCICEPTORS ,DNA Mutational Analysis ,0302 clinical medicine ,Missense mutation ,ATOPIC-DERMATITIS ,CHAINS ,itch ,Exome sequencing ,Skin ,medicine.diagnostic_test ,small fibre neuropathy ,Medicine (all) ,COL6A5 ,neuropathic pain ,PAIN ,Peripheral Nervous System Diseases ,SODIUM-CHANNELS ,Middle Aged ,Itch ,Neuropathic pain ,Small fibre neuropathy ,Arts and Humanities (miscellaneous) ,Neurology (clinical) ,GABAPENTIN ,Female ,Haploinsufficiency ,medicine.drug ,Joint hypermobility ,Adult ,medicine.medical_specialty ,Gabapentin ,Collagen Type VI ,03 medical and health sciences ,CHRONIC PRURITUS ,medicine ,Humans ,Family Health ,business.industry ,Pruritus ,Genetic Variation ,SMALL FIBER NEUROPATHY ,medicine.disease ,030104 developmental biology ,Immunology ,Skin biopsy ,SENSORY NEURONS ,business ,030217 neurology & neurosurgery - Abstract
Itch is thought to represent the peculiar response to stimuli conveyed by somatosensory pathways shared with pain through the activation of specific neurons and receptors. It can occur in association with dermatological, systemic and neurological diseases, or be the side effect of certain drugs. However, some patients suffer from chronic idiopathic itch that is frequently ascribed to psychological distress and for which no biomarker is available to date. We investigated three multigenerational families, one of which diagnosed with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), characterized by idiopathic chronic itch with predominantly proximal distribution. Skin biopsy was performed in all eight affected members and revealed in six of them reduced intraepidermal nerve fibre density consistent with small fibre neuropathy. Whole exome sequencing identified two COL6A5 rare variants co-segregating with chronic itch in eight affected members and absent in non-affected members, and in one unrelated sporadic patient with type 1 painless diabetic neuropathy and chronic itch. Two families and the diabetic patient carried the nonsense c.6814G>T (p.Glu2272*) variant and another family carried the missense c.6486G>C (p.Arg2162Ser) variant. Both variants were predicted as likely pathogenic by in silico analyses. The two variants were rare (minor allele frequency < 0.1%) in 6271 healthy controls and absent in 77 small fibre neuropathy and 167 JHS/EDS-HT patients without itch. Null-allele test on cDNA from patients' fibroblasts of both families carrying the nonsense variant demonstrated functional haploinsufficiency due to activation of nonsense mediated RNA decay. Immunofluorescence microscopy and western blotting revealed marked disorganization and reduced COL6A5 synthesis, respectively. Indirect immunofluorescence showed reduced COL6A5 expression in the skin of patients carrying the nonsense variant. Treatment with gabapentinoids provided satisfactory itch relief in the patients carrying the mutations. Our findings first revealed an association between COL6A5 gene and familiar chronic itch, suggesting a new contributor to the pathogenesis of neuropathic itch and identifying a new candidate therapeutic target.
- Published
- 2017
29. Expanding clinical spectrum of Caspr2 antibody-associated disease: warning on brainstem involvement and respiratory failure
- Author
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Paolo Pozzi, Davide Rossi Sebastiano, Daniele Cazzato, Silvia Cenciarelli, Francesco Deleo, Roberta Di Giacomo, Francesca Andreetta, Giuseppe Didato, Flavio Villani, Marco de Curtis, and Chiara Pastori
- Subjects
Autoimmune encephalitis ,medicine.medical_specialty ,Ataxia ,business.industry ,Limbic encephalitis ,Dysautonomia ,Disease ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Neurology ,Respiratory failure ,Internal medicine ,Medicine ,030212 general & internal medicine ,Neurology (clinical) ,Respiratory system ,medicine.symptom ,Cognitive decline ,business ,030217 neurology & neurosurgery - Abstract
We report the case of a 68-year-old man who presented with ataxia, insomnia, rapidly developing cognitive decline, seizures and small vessel vasculitis. Both serum and cerebro-spinal fluid samples showed positive titre of anti-CASPR2 antibodies. Limbic encephalitis was diagnosed and immunomodulatory therapy was started with benefit. After one-year follow-up, the patient relapsed with a difficult-to-treat respiratory failure, brainstem involvement, neuropathic pain and severe dysautonomia with esophageal dysfunction. We discuss here the occurrence of life-threating complication such as respiratory dysfunction in CASPR2 limbic encephalitis. Furthermore, we showed different phenotype and treatment response during disease onset compared to relapse. This case expands the clinical spectrum of anti-CASPR2 associated disease, underlying the need for respiratory and sleep evaluation.
- Published
- 2020
30. Late-onset and fast progressive neuropathy and cardiomyopathy in Val32Ala transthyretin gene mutation
- Author
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Daniele Cazzato, Eleonora Dalla Bella, Giuseppe Lauria, Gianluca Marucci, Paola Saveri, and Franco Taroni
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Male ,medicine.medical_specialty ,Pathology ,Neurology ,Cardiomyopathy ,Late onset ,Dermatology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Sural Nerve ,medicine ,Humans ,Prealbumin ,030212 general & internal medicine ,Mutation ,Amyloid Neuropathies, Familial ,biology ,business.industry ,Dysautonomia ,General Medicine ,Middle Aged ,medicine.disease ,Pedigree ,Psychiatry and Mental health ,Transthyretin ,biology.protein ,Disease Progression ,Neurology (clinical) ,Neurosurgery ,medicine.symptom ,business ,Cardiomyopathies ,030217 neurology & neurosurgery ,Rare disease - Abstract
More than 100 mutations of the transthyretin gene have been reported in autosomal dominant familial amyloid polyneuropathy. This rare disease causes severe motor and sensory disability, dysautonomia, and in some patients also cardiomyopathy. The diagnosis can be challenging mainly in sporadic adult patients showing clinical, laboratory, and neurophysiological findings overlapping other forms of chronic neuropathy. We describe the clinical features and course of a patient harboring the rare p.V32A (c.155T>C) variant that was previously described in only two patients and whose pathogenicity was unclear.
- Published
- 2018
31. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH) : a randomised, double-blind, placebo-controlled, phase 3 trial
- Author
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Michael Schroeter, Mazen M. Dimachkie, J. Zschuentssch, Takuya Ohkubo, Kenichi Kaida, M. Bednar, M. Tomiyama, J. Sussova, D. Mueller, E. Chi-Ho Lai, Nicolette C. Notermans, Toomas Toomsoo, C. D'Amour, J. Haas, B. Murinson, Masahiro Mori, Richard A. Lewis, Masayuki Baba, Anne D. Sperfeld, Vivian E. Drory, Hans-Peter Hartung, J. Demeestere, Satoshi Kuwabara, Leslie Roberts, S. Mumfrey, David Gosal, Katrin Gross-Paju, M. Zibetti, Martin Vališ, Filip Eftimov, David Yarnitsky, D. Aufauvre, G. Le Masson, Takashi Kanda, Lisa D. Hobson-Webb, I. Melamed, Alexander Shtilbans, Inna Rubanovits, P. MacDonald, Janneke G. J. Hoeijmakers, Vera Bril, Ericka Simpson, Orell Mielke, Michaela Praus, Martin Stangel, Masahiro Iijima, Richard J. Barohn, Robert D. Henderson, P. Baum, Mari Auranen, David Walk, Said R. Beydoun, A. Jaspert-Grehl, Alessandro Testori, Giovanni Antonini, Ingemar S. J. Merkies, Sabrina Matà, A. Di Muzio, Ivo N. van Schaik, T. Kalous, Josep Gamez, Juliane Klehmet, Dario Cocito, Angelo Schenone, R. Carne, P. Kunc, Dale J. Lange, Miriam Freimer, S. Muley, Norman Latov, T. Rao, Jens Ejbye Schmidt, Jasper M. Morrow, Ari Breiner, C. Marquez Infante, C. G. Faber, U. Chyrchel-Paszkiewicz, Anne-Cécile Wielanek-Bachelet, Russell L. Chin, John-Philip Lawo, I. N. van Schaik, C. Goerlitz, M. Chatzopoulos, Tim Hagenacker, Claudia Sommer, H. Johl, D. Kramer, Stefania Morino, R. Yoon, Daniela M. Menichella, M. Alberti Aguiló, K. Nishiyama, Daniele Cazzato, F. Bethke, Helmar C. Lehmann, Konrad Rejdak, T. Lavin, Kazumasa Yokoyama, Olaf Hoffmann, M. Kawai, C. Casanovas Pons, Sandro Sorbi, Takanori Yokota, Nora A. Visser, R. Talab, Eroboghene E. Ubogu, Florian Then Bergh, Stefan Blum, Ginna Gonzalez, J. Oechtering, David R. Cornblath, F. Ciccocioppo, A. Sabet, Fabian Klostermann, Nan van Geloven, K. George, A. Kutschenko, S. Benitez Rivero, Karissa L. Gable, Michael P. Lunn, Senda Ajroud-Driss, Shahram Attarian, Marina Grandis, P. Van Damme, C. Trebst, Jeffrey A. Allen, A. Algom, H. Onoue, D. Liebetanz, Billie L. Durn, Maria Salvado Figueras, Jean Pouget, Emilien Delmont, Khema Sharma, Gen Sobue, K. Ohyama, John T. Kissel, K. Kanai, Tsugio Akutsu, Pierre Clavelou, Andreas Meisel, Giuseppe Lauria, M. Saarela, S. Larue, R. Gold, U. Sorro, Shafeeq Ladha, Claude Desnuelle, P. Berlit, Neurologian yksikkö, Clinicum, HUS Neurocenter, ANS - Neuroinfection & -inflammation, AII - Inflammatory diseases, Other departments, Neurology, AII - Amsterdam institute for Infection and Immunity, Hagenacker, Tim (Beitragende*r), and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience
- Subjects
0301 basic medicine ,Male ,SATISFACTION ,Clinical Trial, Phase III ,Medizin ,Chronic inflammatory demyelinating polyneuropathy ,THERAPY ,3124 Neurology and psychiatry ,law.invention ,MUSCLE STRENGTH ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,law ,QUALITY-OF-LIFE ,Chronic Inflammatory Demyelinating ,Subcutaneous ,Absolute risk reduction ,IGG SELF-INFUSIONS ,Middle Aged ,Clinical Trial ,3. Good health ,Randomized Controlled Trial ,POLYRADICULONEUROPATHY ,Female ,aged ,double-blind method ,female ,humans ,immunoglobulins ,immunologic factors ,injections, subcutaneous ,male ,middle aged ,polyradiculoneuropathy ,chronic inflammatory demyelinating ,outcome assessment (health care) ,neurology (clinical) ,medicine.medical_specialty ,Injections, Subcutaneous ,Clinical Neurology ,Immunoglobulins ,CIDP ,Placebo ,Injections ,03 medical and health sciences ,Outcome Assessment (Health Care) ,Phase III ,Double-Blind Method ,Internal medicine ,medicine ,Journal Article ,Humans ,Immunologic Factors ,HOME ,Adverse effect ,Aged ,business.industry ,ICE ,3112 Neurosciences ,Polyradiculoneuropathy ,medicine.disease ,Surgery ,Clinical trial ,030104 developmental biology ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,PRIMARY ANTIBODY DEFICIENCIES ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Mika Saarela työryhmän jäsenenä. Background Approximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo. Methods Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0.2 g/kg or 0.4 g/kg of a 20% SCIg solution (IgPro20) weekly versus placebo (2% human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1: 1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials. gov, number NCT01545076. Findings In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33%) to the placebo group, 57 (33%) to the low-dose group, and 58 (34%) to the high-dose group. In the intention-to-treat set, 36 (63% [95% CI 50-74]) patients on placebo, 22 (39% [27-52]) on low-dose SCIg, and 19 (33% [22-46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0.0007). Absolute risk reductions were 25% (95% CI 6-41) for low-dose versus placebo (p=0.007), 30% (12-46) for high-dose versus placebo (p=0.001), and 6% (-11 to 23) for high-dose versus low-dose (p=0.32). Causally related adverse events occurred in 47 (27%) patients (ten [18%] in the placebo group, 17 [30%] in the low-dose group, and 20 [34%] in the high-dose group). Six (3%) patients had 11 serious adverse events: one (2%) patient in the placebo group, three (5%) in the low-dose group, and two (3%) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related. Interpretation This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP.
- Published
- 2018
32. Intravenous versus subcutaneous immunoglobulin – Authors' reply
- Author
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Ivo N van Schaik, Orell Mielke, Arman Sabet, Koshy George, Leslie Roberts, Ross Carne, Stefan Blum, Robert Henderson, Philip Van Damme, Jelle Demeestere, Sandrine Larue, Catherine-Andree Pinard D'Amour, Vera Bril, Ari Breiner, Pavel Kunc, Martin Valis, Jana Sussova, Tomas Kalous, Radomir Talab, Michal Bednar, Toomas Toomsoo, Inna Rubanovits, Katrin Gross-Paju, Ulvi Sorro, Mika Saarela, Mari Auranen, Jean Pouget, Shahram Attarian, Gwendal Le Masson, Anne-Cécile Wielanek-Bachelet, Claude Desnuelle, Emilien Delmont, Pierre Clavelou, Dominique Aufauvre, Jens Schmidt, Jana Zschuentssch, Claudia Sommer, Daniela Kramer, Olaf Hoffmann, Carsten Goerlitz, Judith Haas, Marko Chatzopoulos, Min-Suk Yoon, Ralf Gold, Peter Berlit, Andrea Jaspert-Grehl, David Liebetanz, Anna Kutschenko, Martin Stangel, Corinna Trebst, Petra Baum, Florian Then Bergh, Juliane Klehmet, Andreas Meisel, Fabian Klostermann, Johanna Oechtering, Helmar Lehmann, Michael Schroeter, Tim Hagenacker, Daniel Mueller, Anne-Dorte Sperfeld, Florian Bethke, Hans-Peter Hartung, Vivian Drory, Avi Algom, David Yarnitsky, Beth Brianna Murinson, Antonio Di Muzio, Fausta Ciccocioppo, Sandro Sorbi, Sabrina Mata, Angelo Schenone, Marina Grandis, Giuseppe Lauria, Daniele Cazzato, Giovanni Antonini, Stefania Morino, Dario Cocito, Maurizio Zibetti, Takanori Yokota, Takuya Ohkubo, Takashi Kanda, Motoharu Kawai, Kenichi Kaida, Hiroyuki Onoue, Satoshi Kuwabara, Masahiro Mori, Masahiro Iijima, Ken Ohyama, Gen Sobue, Masayuki Baba, Masahiko Tomiyama, Kazutoshi Nishiyama, Tsugio Akutsu, Kazumasa Yokoyama, Kazuaki Kanai, Ivo N. van Schaik, Filip Eftimov, Nicolette. C. Notermans, Nora. A. Visser, Catharina Faber, Janneke. G.J. Hoeijmakers, Ingemar S.J. Merkies, Nan van Geloven, Konrad Rejdak, Urszula Chyrchel-Paszkiewicz, Carlos Casanovas Pons, María Antonia Alberti Aguiló, Josep Gamez, María Figueras, Celedonio Marquez Infante, Sonia Benitez Rivero, Michael Lunn, Jasper Morrow, David Gosal, Timothy Myles Lavin, Isaac Melamed, Alessandro Testori, Senda Ajroud-Driss, Daniela Menichella, Ericka Simpson, Eugene Chi-Ho Lai, Mazen Dimachkie, Richard J. Barohn, Said Beydoun, Harpreet Johl, Dale Lange, Alexander Shtilbans, Suraj Muley, Shafeeq Ladha, Miriam Freimer, John Kissel, Norman Latov, Russell Chin, Eroboghene Ubogu, Sandi Mumfrey, T. Hermanth P. Rao, Paul MacDonald, Khema Sharma, Ginna Gonzalez, Jeffrey Allen, David Walk, Lisa Hobson-Webb, Karissa Gable, Richard A. Lewis, David R. Cornblath, John-Phillip Lawo, Michaela Praus, Billie L. Durn, Hagenacker, Tim (Beitragende*r), Amsterdam Neuroscience - Neuroinfection & -inflammation, AII - Inflammatory diseases, and Neurology
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Medizin ,Immunoglobulins, Intravenous ,Chronic inflammatory demyelinating polyneuropathy ,Subcutaneous immunoglobulin ,medicine.disease ,Gastroenterology ,Pharmacokinetics ,Internal medicine ,biology.protein ,medicine ,Administration, Intravenous ,Neurology (clinical) ,Antibody ,business - Abstract
We thank Ravi Uniyal and colleagues for their comments on our results from the PATH trial1 on subcutaneous immunoglobulin (SCIg) for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). They express concern about the relapse rates in the treatment groups and hypothesise the cause being the pharmacokinetics of SCIg.
- Published
- 2018
33. Neurological Pain
- Author
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Daniele Cazzato and Giuseppe Lauria
- Published
- 2015
34. MOLECULAR INVERSION PROBE-TARGETED GENERATION SEQUENCING TO IDENTIFY GENETIC MARKERS IN PAINFUL NEUROPATHIES - THE PROPANE STUDY
- Author
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Gerrits, M. M., Almomani, R., Lindsey, P., Marchi, M., Hoeijmakers, J. G. J., Merkies, I. S. J., Fadavi, H., Malik, R., Ziegler, D., Boenhof, G., Martinelli-Boneschi, F., Santoro, S., Daniele Cazzato, Lombardi, R., Dib-Hajj, S. D., Waxman, S. G., Smeets, H. J. M., Faber, C. G., and Lauria, G.
35. Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes
- Author
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Giuseppe Lauria, Paola Grammatico, Eleonora Dalla Bella, Francesca Caravello, Chiara Dordoni, Marco Castori, Marina Colombi, Raffaella Lombardi, Antonio Petrucci, and Daniele Cazzato
- Subjects
0301 basic medicine ,Joint hypermobility ,Adult ,Male ,medicine.medical_specialty ,Biopsy ,Small Fiber Neuropathy ,Neural Conduction ,Pain ,Nerve fiber ,Sural nerve ,Medicine (all) ,Neurology (clinical) ,Ehlers-Danlos syndrome ,small fiber neuropathy ,pain ,Nerve conduction velocity ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Sural Nerve ,medicine ,Humans ,Pain Measurement ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Dermatology ,030104 developmental biology ,medicine.anatomical_structure ,Neuropathic pain ,Skin biopsy ,Ehlers-Danlos Syndrome ,Female ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS).Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex- and age-adjusted normative reference values.Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS ≥4 and7) in 8 patients and severe (NRS ≥7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type.SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS.
36. VARIANT-TO-GENE APPROACH: SCOUTING THE GENETIC RISK FACTOR IN AN ITALIAN COHORT WITH PAINFUL SMALL FIBRE NEUROPATHY
- Author
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Marchi, M., Salvi, E., D Amato, I., Daniele Cazzato, Lombardi, R., Paolini, M., Devigili, G., Gerrits, M., Faber, C., and Lauria, G.
37. SIDE AND TIME VARIABILITY OF INTRAEPIDERMAL NERVE FIBER DENSITY
- Author
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Jenny Sassone, Patrizia Dacci, Christian Lettieri, Daniele Cazzato, Sara Rinaldo, Eleonora Dalla Bella, Giuseppe Lauria, Carla Porretta-Serapiglia, Michela Taiana, Grazia Devigili, Roberto Eleopra, Raffaella Lombardi, Lauria, Giuseppe, Dacci, Patrizia, Lombardi, Raffaella, Cazzato, Daniele, Porretta Serapiglia, Carla, Taiana, Michela, SASSONE PAGANO, Jenny, Dalla Bella, Eleonora, Rinaldo, Sara, Lettieri, Christian, Eleopra, Roberto, and Devigili, Grazia
- Subjects
Adult ,Male ,medicine.medical_specialty ,Biopsy ,Neural Conduction ,Sural nerve ,Nerve fiber ,Audiology ,Young Adult ,Nerve Fibers ,Healthy volunteers ,medicine ,Humans ,In patient ,Small Fiber Neuropathy ,Leg ,medicine.diagnostic_test ,business.industry ,Distal site ,Peripheral Nervous System Diseases ,Reproducibility of Results ,Middle Aged ,medicine.anatomical_structure ,Skin biopsy ,Neurology (clinical) ,Epidermis ,business ,Nuclear medicine - Abstract
Objective: To assess the right-to-left and short-term variability of intraepidermal nerve fiber density (IENFD) at the distal site of the leg. Methods: Patients with possible or probable small fiber neuropathy (SFN) and healthy volunteers (HVs) underwent skin biopsies at the right and left distal leg. A subgroup of participants underwent follow-up biopsies 20 days later. Biopsies were immunostained by polyclonal anti-protein gene product 9.5 antibodies, and IENFD was quantified in nonconsecutive sections following published guidelines by operators blinded to the participants9 condition (diagnosis, side, and time of biopsy). Findings were referred to sex- and age-adjusted normative values. Results: Forty patients and 17 HVs underwent bilateral skin biopsies; 15 patients and 8 HVs underwent follow-up skin biopsies. Sural nerve and dorsal sural nerve conduction studies were normal in all participants. Interside IENFD did not differ both in patients (median 2.45 IENF/mm ± 1.45 SD right; 2.2 IENF/mm ± 1.32 SD left) and HVs (median 6.3 IENF/mm ± 2.81 right; 6.2 IENF/mm ± 2.3 SD left). The right-to-left correlation coefficients were excellent (Pearson 0.95 in SFN and 0.97 in HVs). The analysis of IENFD at 20-day follow-up biopsy showed no difference between sides in both groups and yielded excellent correlation coefficients. Conclusions: The diagnosis of SFN can be reliably ascertained by unilateral skin biopsy at the distal site of the leg, and IENFD is not expected to vary within 3 weeks.
38. DEVELOPMENT AND OPTIMIZATION OF A PROTOCOL FOR RNA EXTRACTION FROM HUMAN SKIN BIOPSY OF PATIENTS AFFECTED BY PAINFUL AND PAINLESS PERIPHERAL NEUROPATHY
- Author
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Santoro, S., Lopez, I. D., Daniele Cazzato, Sorosina, M., Zauli, A., Grevendonk, L., Lombardi, R., Marchi, M., Faber, C. G., Gerrits, M. M., Almomani, R., Hoeijmakers, J. G. J., Merkies, I. S. J., Fadavi, H., Malik, R., Ziegler, D., Boenhof, G., Comi, G., Dib-Hajj, S. D., Waxman, S. G., Quattrini, A., Lauria, G., Boneschi, Martinelli F., Santoro, S, Lopez, Id, Cazzato, D, Sorosina, M, Zauli, A, Grevendonk, L, Lombardi, R, Marchi, M, Faber, Cg, Gerrits, Mm, Almomani, R, Hoeijmakers, Jgj, Merkies, Isj, Fadavi, H, Malik, R, Ziegler, D, Boenhof, G, Comi, Giancarlo, Dib Hajj, Sd, Waxman, Sg, Quattrini, A, Lauria, G, and Boneschi, Fm
39. CEREBELLAR ATAXIA, NEUROPATHY, AND VESTIBULAR AREFLEXIA SYNDROME: A SLOWLY PROGRESSIVE DISORDER WITH STEREOTYPICAL PRESENTATION
- Author
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Giuseppe Lauria, Caterina Mariotti, Eleonora Dalla Bella, Daniele Cazzato, and Patrizia Dacci
- Subjects
Adult ,Male ,medicine.medical_specialty ,Neurology ,Cerebellar Ataxia ,Sensory system ,Nystagmus ,Audiology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030223 otorhinolaryngology ,Aged ,Vestibular system ,Aged, 80 and over ,Vestibular areflexia ,Cerebellar ataxia ,Limb ataxia ,Peripheral Nervous System Diseases ,Reflex, Vestibulo-Ocular ,Syndrome ,Middle Aged ,Vestibular Function Tests ,Cerebellar atrophy ,Female ,Neurology (clinical) ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery - Abstract
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a newly described condition with onset in adulthood, characterized by progressive balance impairment and sensory disturbances in the lower limbs, which can severely affect patients' quality of life. Its pathogenesis remains obscure and the diagnosis challenging. We described four patients complaining of slowly progressive gait unbalance and sensory disturbances at the feet followed, after a period ranging 2-6 years, by cerebellar dysfunction. All patients showed gait and limb ataxia, positive Romberg sign, cerebellar dysarthria, gaze-evoked nystagmus, absent deep tendon reflexes, and impaired vibratory sensation. Nerve conduction studies revealed axonal sensory neuropathy, brain magnetic resonance imaging showed cerebellar atrophy, and otoneurological investigation demonstrated bilateral vestibular areflexia with impaired vestibulo-ocular reflexes. The diagnosis of CANVAS should be suspected on clinical ground based on homogeneous course of symptoms and signs, and addressed by video-oculography eye movement recording.
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