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1. A cross-sectional study investigating frequency and features of definitely diagnosed diabetic painful polyneuropathy

Author

Truini, A, Spallone, V, Morganti, R, Tamburin, S, Zanette, G, Schenone, A, De Michelis, C, Tugnoli, V, Simioni, V, Manganelli, F, Dubbioso, R, Lauria, G, Lombardi, R, Jann, S, De Toni Franceschini, L, Tesfaye, S, Fiorelli, M, Spagnoli, A, Cruccu, G, Marfia, Ga, Truini, Andrea, Spallone, Vincenza, Morganti, Roberto, Tamburin, Stefano, Zanette, Giampietro, Schenone, Angelo, De Michelis, Chiara, Tugnoli, Valeria, Simioni, Valentina, Manganelli, Fiore, Dubbioso, Raffaele, Lauria, Giuseppe, Lombardi, Roberta, Jann, Stefano, De Toni Franceschini, Luisa, Tesfaye, Solomon, Fiorelli, Marco, Spagnoli, Alessandra, and Cruccu, Giorgio

Subjects
Male, Pediatrics, Diabetic neuropathy, Biopsy, Neural Conduction, Neuropathic pain, Settore MED/13 - Endocrinologia, 0302 clinical medicine, Diabetic Neuropathies, Outpatient clinic, Prospective Studies, Prospective cohort study, Pain Measurement, Skin, Aged, 80 and over, Neurologic Examination, Small-fibre neuropathy, medicine.diagnostic_test, small fibre neuropathy, Diabetes, Middle Aged, Neurology, Nerve conduction study, Settore MED/26 - Neurologia, Polyneuropathy, Adult, medicine.medical_specialty, neuropathic pain, peripheral neuropathy, diabetes, Small Fiber Neuropathy, 030209 endocrinology & metabolism, Physical examination, Young Adult, 03 medical and health sciences, Diabetes mellitus, medicine, Humans, Aged, business.industry, medicine.disease, Neurology (clinical), Anesthesiology and Pain Medicine, Cross-Sectional Studies, diabete, Skin biopsy, Neuralgia, diabetic neuropathy, neuropathic pain, small fibre neuropathy, Complication, business, 030217 neurology & neurosurgery
Abstract

This cross-sectional multicentre study aimed at investigating frequency and features of painful diabetic polyneuropathyWe consecutively enrolled 816 patients attending hospital diabetic outpatient clinics. We first definitely diagnosed diabetic polyneuropathy and pure small-fibre polyneuropathy using clinical examination, nerve conduction study, and skin biopsy or quantitative sensory testing. Adhering to widely agreed criteria, we then identified neuropathic pain and diagnosed painful polyneuropathy using a combined approach of clinical examination and diagnostic testsOut of the 816 patients, 36% had a diabetic polyneuropathy associated with male gender, age and diabetes severity; 2.5% of patients had a pure small-fibre polyneuropathy, unrelated to demographic variables and diabetes severity. Of the 816 patients, 115 (13%) suffered from a painful polyneuropathy, with female gender as the only risk factor for suffering from painful polyneuropathyIn this large study, providing a definite diagnosis of diabetic polyneuropathy and pure small-fibre polyneuropathy, we show the frequency of painful polyneuropathy, and demonstrate that this difficult to treat complication is more common in women than in men.

Published
2018

2. A Multicentric Prospective Incidence Study of Guillain-Barré Syndrome in Italy. The ITANG Study

Author

Benedetti, M, Pugliatti, M, Dalessandro, R, BEGHI, ETTORE, Chiò, A, Logroscino, G, Filippini, G, Galeotti, F, Massari, M, Santuccio, C, Raschetti, R, Abruzzi, L, Agazzi, E, Agostoni, E, Ambrogio, L, Amidei, S, Arbasino, C, Argentiero, V, Arnaboldi, M, Baldini, D, Barki, R, Bassi, P, Basso, F, Belcastro, V, Bellotti, M, Bersano, E, Besana, R, Bettoni, L, Bezzi, G, Bianconi, C, Bondavalli, M, Bonometti, A, Borghi, AM, Borsato, C, Bortolotto, S, Bottacchi, EF, Bresolin, N, Bruno, S, Burlina, A, Cafasso, G, Callegarini, C, Calvo, A, Candeloro, E, Casano, A, Cattaneo, SI, Cavallo, R, Cheldi, A, Ciardo, G, Cirignotta, F, Clerici, AM, Clerici, R, Comi, G, Conti, R, Coppo, F, Covelli, V, Crespi, V, Currò Dossi, M, Curtò, NA, D'Adda, E, Dallocchio, C, D'Anna, S, De Massis, P, De Toni Franceschini, L, Di Vito, N, Didonè, G, Dileone, M, Donati, E, Dotta, M, Fazio, R, Federico, F, FERRARESE, CARLO, Ferrazzini, F, Ferrero, B, Filosto, M, Frasson, E, Fusina, S, Galbussera, A, Gastaldo, E, Geda, C, Ghiglione, P, Giometto, B, Gionco, M, Giorgetti, A, Giussani, G, Gobbin, F, Grampa, G, Granieri, E, Greco, G, Guidetti, D, Guidi, C, Guidotti, M, Gusmaroli, G, Imperiale, D, Internò, S, Jann, S, La Spina, I, Leo, A, Leone, M, Leoni, S, Leotta, D, Lerario, R, Liotta, G, Livrea, P, Luda di Cortemiglio, E, Maggio, B, Magni, E, Magnoni, A, Maistrelli, J, Manca, D, Mandrioli, J, Manera, U, Marcello, N, Marchi, P, Marchini, C, Marconi, S, Mattioli, M, Mauro, A, Mazzaglia, G, Medici, D, Meineri, P, Meola, G, Micaglio, G, Michelucci, R, Michieli, G, Micieli, G, Minardi, C, Moglia, C, Monaco, S, Montanari, E, Moretto, G, Munerati, V, Mura, G, Mussutto, V, Nascimbene, C, Neri, W, Nichelli, P, Nobile Orazio, E, Oddenino, E, Onorato, S, Padovani, A, Palermo, M, Papurello, DM, Passarella, B, Pavesi, G, Penza, MT, Perini, M, Perini, F, Perla, F, Perlotto, N, Perrone, P, Pignatta, P, Pisano, F, Poglio, F, Polo, A, Poloni, M, Porazzi, D, Pradotto, L, Previdi, P, Quatrale, R, Rasi, F, Ravasio, A, Ravetti, C, Repaci, M, Riccardi, T, Riguzzi, P, Rinaldi, R, Riva, M, Romeo, V, Romorini, A, Rosso, T, Rotondo, G, Sacquegna, T, Sanson, F, Santamato, V, Santoro, D, Sartori, V, Sasanelli, F, Savio, K, Serena, M, Silani, V, Silvestri, L, Simioni, V, Squintani, GM, Suardelli, M, Tartagla, L, Terenghi, F, Terlizzi, E, Terzano, M, Tesser, F, Testa, L, Ticca, A, Ticozzi, N, Tiriticco, M, Tola, MR, Tonietti, S, Trianni, G, Trojano, M, Trotta, F, Turatti, M, Ursino, E, Vanotti, A, Vercellino, M, Villani, A, Vitelli, E, Zambito Marsala, S, Zanette, G, Zarcone, D, Zimatore, G, Zoccolella, S., Benedetti, Md, Pugliatti, M, D'Alessandro, R, Beghi, E, Chiò, A, Logroscino, G, Filippini, G, Galeotti, F, Massari, M, Santuccio, C, Comi, Giancarlo, Raschetti, R, ITANG Study, Group, Giometto, B, Benedetti, M, Dalessandro, R, Abruzzi, L, Agazzi, E, Agostoni, E, Ambrogio, L, Amidei, S, Arbasino, C, Argentiero, V, Arnaboldi, M, Baldini, D, Barki, R, Bassi, P, Basso, F, Belcastro, V, Bellotti, M, Bersano, E, Besana, R, Bettoni, L, Bezzi, G, Bianconi, C, Bondavalli, M, Bonometti, A, Borghi, A, Borsato, C, Bortolotto, S, Bottacchi, E, Bresolin, N, Bruno, S, Burlina, A, Cafasso, G, Callegarini, C, Calvo, A, Candeloro, E, Casano, A, Cattaneo, S, Cavallo, R, Cheldi, A, Ciardo, G, Cirignotta, F, Clerici, A, Clerici, R, Comi, G, Conti, R, Coppo, F, Covelli, V, Crespi, V, Currò Dossi, M, Curtò, N, D'Adda, E, Dallocchio, C, D'Anna, S, De Massis, P, De Toni Franceschini, L, Di Vito, N, Didonè, G, Dileone, M, Donati, E, Dotta, M, Fazio, R, Federico, F, Ferrarese, C, Ferrazzini, F, Ferrero, B, Filosto, M, Frasson, E, Fusina, S, Galbussera, A, Gastaldo, E, Geda, C, Ghiglione, P, Gionco, M, Giorgetti, A, Giussani, G, Gobbin, F, Grampa, G, Granieri, E, Greco, G, Guidetti, D, Guidi, C, Guidotti, M, Gusmaroli, G, Imperiale, D, Internò, S, Jann, S, La Spina, I, Leo, A, Leone, M, Leoni, S, Leotta, D, Lerario, R, Liotta, G, Livrea, P, Luda di Cortemiglio, E, Maggio, B, Magni, E, Magnoni, A, Maistrelli, J, Manca, D, Mandrioli, J, Manera, U, Marcello, N, Marchi, P, Marchini, C, Marconi, S, Mattioli, M, Mauro, A, Mazzaglia, G, Medici, D, Meineri, P, Meola, G, Micaglio, G, Michelucci, R, Michieli, G, Micieli, G, Minardi, C, Moglia, C, Monaco, S, Montanari, E, Moretto, G, Munerati, V, Mura, G, Mussutto, V, Nascimbene, C, Neri, W, Nichelli, P, Nobile Orazio, E, Oddenino, E, Onorato, S, Padovani, A, Palermo, M, Papurello, D, Passarella, B, Pavesi, G, Penza, M, Perini, M, Perini, F, Perla, F, Perlotto, N, Perrone, P, Pignatta, P, Pisano, F, Poglio, F, Polo, A, Poloni, M, Porazzi, D, Pradotto, L, Previdi, P, Quatrale, R, Rasi, F, Ravasio, A, Ravetti, C, Repaci, M, Riccardi, T, Riguzzi, P, Rinaldi, R, Riva, M, Romeo, V, Romorini, A, Rosso, T, Rotondo, G, Sacquegna, T, Sanson, F, Santamato, V, Santoro, D, Sartori, V, Sasanelli, F, Savio, K, Serena, M, Silani, V, Silvestri, L, Simioni, V, Squintani, G, Suardelli, M, Tartagla, L, Terenghi, F, Terlizzi, E, Terzano, M, Tesser, F, Testa, L, Ticca, A, Ticozzi, N, Tiriticco, M, Tola, M, Tonietti, S, Trianni, G, Trojano, M, Trotta, F, Turatti, M, Ursino, E, Vanotti, A, Vercellino, M, Villani, A, Vitelli, E, Zambito Marsala, S, Zanette, G, Zarcone, D, Zimatore, G, and Zoccolella, S

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Epidemiology, Population, Guillain-Barre Syndrome, Rate ratio, NO, Young Adult, Axonal and demyelinating GBS, Guillain-Barré syndrome, Incidence, Prospective study, Trend, Neurology (clinical), Aged, Aged, 80 and over, Female, Humans, Italy, Middle Aged, 80 and over, medicine, Young adult, education, Prospective cohort study, education.field_of_study, Guillain-Barre syndrome, business.industry, Medicine (all), Incidence (epidemiology), medicine.disease, Vaccination, Settore MED/26 - NEUROLOGIA, business, Human
Abstract

Background: To assess Guillain-Barré syndrome (GBS) incidence we relied on the Italian Network for the study of GBS (ITANG) established in 2010 in 7 Italian regions to analyse the association between influenza vaccination and GBS. Methods: All individuals aged ≥18 years, presenting with clinical manifestations that suggested GBS according to the universally accepted Asbury's diagnostic criteria (1990) were prospectively notified to a centralised database by ITANG neurologists over the period October 1, 2010-September 30, 2011. Through a telephone survey, 9 trained interviewers followed up the cases to diagnosis and then for 1 year since hospital discharge. Validation of case reporting was performed with the support of administrative data in 5 regions. Results: We found 365 cases fulfilling the definition for GBS or one of its variants over 19,846,068 population ≥18 years of age, yielding an annual incidence rate of 1.84 per 100,000 (95% CI 1.65-2.03), 2.30 (95% CI 1.99-2.60) in men and 1.41 (95% CI 1.18-1.64) in women. A highly significant peak of incidence was observed in February 2011 as compared to reference month (September 2011, rate ratio 3.3:1, p < 0.01). Conclusions: In Italy, GBS incidence was among the highest reported in Europe and higher than previously observed in Italian studies.

Published
2015

3. Multicenter case-control study on restless legs syndrome in multiple sclerosis: The REMS Study

Author

Rems, Italian Study Group, Manconi M, Ferini-Strambi L, Filippi M, Bonanni E, Iudice A, Murri L, Gl, Gigli, Fratticci L, Merlino G, Terzano G, Granella F, Parrino L, Silvestri R, Aricò I, Dattola V, Russo G, Luongo C, Cicolin A, Tribolo A, Cavalla P, Savarese M, Trojano M, Ottaviano S, Cirignotta F, Simioni V, Salvi F, Mondino F, Perla F, Chinaglia G, Zuliani C, Cesnik E, Enrico Granieri, Placidi F, Mg, Palmieri, Manni R, Terzaghi M, Bergamaschi R, Rocchi R, Ulivelli M, Bartalini S, Ferri R, Lo Fermo S, Ubiali E, Viscardi M, Rottoli M, Nobili L, Protti A, Ferrillo F, Allena M, Mancardi G, Guarnieri B, Londrillo F, Manconi, M, FERINI STRAMBI, Luigi, Filippi, Massimo, Bonanni, E, Iudice, A, Murri, L, Gigli, Gl, Fratticci, L, Merlino, G, Terzano, G, Granella, F, Parrino, L, Silvestri, R, Arico, I, Dattola, V, Russo, G, Luongo, C, Cicolin, A, Tribolo, A, Cavalla, P, Savarese, M, Trojano, M, Ottaviano, S, Cirignotta, F, Simioni, V, Salvi, F, Mondino, F, Perla, F, Chinaglia, G, Zuliani, C, Cesnik, E, Granieri, E, Placidi, F, Palmieri, Mg, Manni, R, Terzaghi, M, Bergamaschi, R, Rocchi, R, Ulivelli, M, Bartalini, S, Ferri, R, Lo Fermo, S, Ubiali, E, Viscardi, M, Rottoli, M, Nobili, L, Protti, A, Ferrillo, F, Allena, M, Mancardi, G, Guarnieri, B, and Londrillo, F.

Subjects
Male, demography, trazodone, insomnia, amitriptyline, Comorbidity, Relapsing-Remitting, Sleep medicine, Hypnotic, alprazolam, Restless legs syndrome, multiple sclerosis, sleep, Sleep Initiation and Maintenance Disorders, Insomnia, citalopram, Prospective Studies, Prospective cohort study, diazepam, lorazepam, prazepam, zolpidem, adult, article, blood examination, clinical trial, controlled study, disease course, disease duration, disease severity, female, health survey, human, major clinical study, male, multicenter study, priority journal, restless legs syndrome, risk factor, Adult, Case-Control Studies, Cross-Sectional Studies, Female, Health Surveys, Humans, Italy, Middle Aged, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting, Restless Legs Syndrome, Chronic Progressive, Settore MED/26 - Neurologia, Sleep onset, medicine.symptom, medicine.medical_specialty, Multiple Sclerosis, medicine.drug_class, Multiple sclerosis, Sleep, NO, Physiology (medical), Internal medicine, mental disorders, medicine, Multiple Sclerosis and Restless Legs Syndrome, diagnosis/epidemiology, business.industry, medicine.disease, Adult, Case-Control Studies, Comorbidity, Cross-Sectional Studies, Female, Health Surveys, Humans, Italy, Male, Middle Aged, Multiple Sclerosis, diagnosis/epidemiology, Multiple Sclerosis, diagnosis/epidemiology, Prospective Studies, Restless Legs Syndrome, diagnosis/epidemiology, Sleep Initiation and Maintenance Disorders, Physical therapy, Neurology (clinical), business
Abstract

Study objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. Design: Prospective, multicenter, case-control epidemiologic survey. Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine. Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects. Interventions: N/A. Measures and results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.

4. Report of a novel ATP7A mutation causing distal motor neuropathy

Author

Alessandra Ferlini, Francesca Gualandi, Mert Karakaya, Rocco Liguori, Stefano Squarzoni, Fernanda Fortunato, V. Simioni, Marcella Neri, Elisabetta Sette, Domenico De Grandis, Alex Incensi, Vincent Timmerman, Markus Storbeck, Rita Selvatici, Valeria Tugnoli, C. Scotton, Brunhilde Wirth, Stefania Bigoni, Vincenzo Donadio, Gualandi F., Sette E., Fortunato F., Bigoni S., De Grandis D., Scotton C., Selvatici R., Neri M., Incensi A., Liguori R., Storbeck M., Karakaya M., Simioni V., Squarzoni S., Timmerman V., Wirth B., Donadio V., Tugnoli V., and Ferlini A.

Subjects
Male, 0301 basic medicine, Proband, Retrograde ejaculation, Pathology, medicine.medical_specialty, Peripheral neuropathy, ATP7A, Occipital horn syndrome, Socio-culturale, medicine.disease_cause, Cutis Laxa, Muscular Atrophy, Spinal, Autonomic neuropathy, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Missense mutation, ATP7A mutation, Motor Neuron Disease, Menkes Kinky Hair Syndrome, Genetic Association Studies, Genetics (clinical), Aged, Adenosine Triphosphatases, Mutation, business.industry, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, Neurology, Copper-Transporting ATPases, Pediatrics, Perinatology and Child Health, Ehlers-Danlos Syndrome, Menkes disease, Human medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

We describe a novel ATP7A gene mutation associated with distal motor neuropathy, mild connective tissue abnormalities and autonomic disturbances. Next-generation sequencing analysis of a lower-motor neuron diseases gene panel was performed in two sibs presenting with distal motor neuropathy plus an autonomic dysfunction, which main manifestations were retrograde ejaculation, diarrhea and hyperhydrosis. Probands underwent dysmorphological, neurological, electrophysiological as well as biochemical evaluations and somatic and autonomic innervation studies on skin biopsies. A novel missense mutation (p.A991D) was identified in the X-linked ATP7A gene, segregating in both brothers and inherited from their healthy mother. Biochemical studies on patients’ blood samples showed reduced serum copper and ceruloplasmin levels. Clinical and neurophysiological evaluation documented dysautonomic signs. Quantitative evaluation of skin innervation disclosed a small fiber neuropathy with prevalent autonomic involvement. Mutations in the ATP7A gene, encoding for a copper-transporting ATPase, have been associated with the severe infantile neurodegenerative Menkes disease and in its milder variant, the Occipital Horn Syndrome. Only two ATP7A mutations were previously reported as causing, a pure axonal distal motor neuropathy (dHMN-SMAX3). The phenotype we report represents a further example of this rare genotype-phenotype correlation and highlights the possible occurrence in SMAX3 of autonomic disturbances, as described for Menkes disease and Occipital Horn Syndrome.

Published
2019
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