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526 results on '"Bisulli, F."'

1. Detection of somatic and germline pathogenic variants in adult cohort of drug-resistant focal epilepsies

Author: Ferri, L., Menghi, V., Licchetta, L., Dimartino, P., Minardi, R., Davì, C., Di Vito, L., Cifaldi, E., Zenesini, C., Gozzo, F., Pelliccia, V., Mariani, V., de Spelorzi, Y.C.C., Gustincich, S., Seri, M., Tassi, L., Pippucci, T., and Bisulli, F.
Published: 2024
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2. Neurological Manifestations of Long COVID: A Single-Center One-Year Experience

Author: Taruffi L, Muccioli L, Mitolo M, Ferri L, Descovich C, Mazzoni S, Michelucci R, Lodi R, Liguori R, Cortelli P, Tonon C, and Bisulli F
Subjects: covid 19, neurocovid, follow-up, cognitive disorders, neuropsychology, hypo/anosmia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Lisa Taruffi,1,&ast; Lorenzo Muccioli,1,&ast; Micaela Mitolo,2,3 Lorenzo Ferri,1 Carlo Descovich,4 Stefania Mazzoni,2 Roberto Michelucci,2 Raffaele Lodi,1,2 Rocco Liguori,1,2 Pietro Cortelli,1,2 Caterina Tonon,1,2 Francesca Bisulli1,2 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 3Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 4Clinical Governance, Research, Education and Quality Improvement Unit, AUSL Bologna, Bologna, Italy&ast;These authors contributed equally to this workCorrespondence: Francesca Bisulli, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, Tel +39 0514966937, Fax +39 05149669993, Email francesca.bisulli@unibo.itPurpose: We report our single-center experience on the neurological manifestations of long COVID.Patients and Methods: This is a retrospective observational study. All consecutive patients referred to the neurological long COVID outpatient clinic of our institute from January 21 2021 to December 9 2021 underwent a general neurological objective examination. Treatments and investigations (brain MRI, neuropsychological evaluation, or others) were prescribed on an individual basis as per standard clinical practice. A follow-up visit was performed when appropriate. Descriptive statistics were presented as absolute and relative frequencies for categorical variables and as means, median, and ranges for continuous variables.Results: One hundred and three patients were visited (mean age 50.5 ± 36 years, 62 females). The average time from acute COVID-19 infection to the first visit to our outpatient clinic was 243 days. Most patients presented with a mild form of acute COVID-19, with only 24 cases requiring hospitalization. The neurological symptoms mostly (n=70/103, 68%) started during the acute phase (before a negative swab for SARS-CoV-2). The most frequent acute manifestations reported, which lately became persistent, were fatigue (n=58/103, 56%), olfactory/taste dysfunction (n=58/103, 56%), headache (n=47/103, 46%), cognitive disorders (n=46/103, 45%), sleep disorders (n=30/103, 29%), sensitivity alterations (n=29/103, 28%), and dizziness (n=7/103, 7%). Tremor was also reported (n=8/103, 7%). Neuropsychological evaluation was performed in 30 patients and revealed alterations in executive functions (n=6/30, 20%), memory (n=11/30, 37%), with pathological depressive (n=9/30, 30%) and anxiety (n=8/30, 27%) scores. Brain MRIs have been performed in 41 cases, revealing nonspecific abnormal findings only in 4 cases. Thirty-six patients underwent a follow-up, where a general improvement was observed but rarely (n=2/36) a complete recovery.Conclusion: The majority of patients presenting persistent neurological symptoms (most frequently fatigue, cognitive disorders, and olfactory dysfunctions) developed a previous mild form of COVID-19. Further studies are required to develop therapeutic strategies.Keywords: COVID 19, neuroCOVID, follow-up, cognitive disorders, neuropsychology, hypo/anosmia
Published: 2023

3. fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study

Author: Vaudano, A. E., Mirandola, L., Talami, F., Giovannini, G., Monti, G., Riguzzi, P., Volpi, L., Michelucci, R., Bisulli, F., Pasini, E., Tinuper, P., Di Vito, L., Gessaroli, G., Malagoli, M., Pavesi, G., Cardinale, F., Tassi, L., Lemieux, L., and Meletti, S.
Published: 2021
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4. Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic : a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Author: Schumacher, A. E., Kyu, H. H., Antony, C. M., Aravkin, A. Y., Azhar, G. S., Bisignano, C., Burkart, K., Cercy, K. M., Chung, E., Coberly, K., Comfort, H., Cousin, E., Culbreth, G. T., Cunningham, M., Weaver, N. D., Degenhardt, L., Deitesfeld, L., Dirac, M. A., Estep, K., Feigin, V. L., Flaxman, A. D., Flor, L. S., Force, L. M., Fuller, J. E., Gakidou, E., Hay, S. I., Ikuta, K. S., Jones, D. P., Kassebaum, N. J., Kassel, M. B., Keller, C., Kinzel, K. E., Krohn, K. J., Lozano, R., May, E. A., McKowen, A. W., McLaughlin, S. A., Mehlman, M. L., Mestrovic, T., Mokdad, A. H., Mosser, J. F., Mougin, V., Naghavi, M., Nesbit, O. D., Novotney, A., Ozten, Y., Pease, S. A., Pigott, D. M., Reiner, R. C., Robinson-Oden, H. E., Shaw, D. H., Slepak, E. L. N., Sorensen, R. J. D., Verghese, N. A., Vollset, S., Vongpradith, A., Vos, T., Wang, D., Watson, S., Weaver, M. R., Wells, K. M., Wilson, S., Wool, E. E., Zheng, P., Lim, S. S., Murray, C. J. L., Boyko, E. J., Chahine, Y., Kalani, R., Krishnamoorthy, V., Khalil, I. A., Minja, N. W., Morrison, S. D., Nafukho, F. M., Olivas-Martinez, A., Orellana, E., Tram, K., Aali, A., Rahnavard, N., Ahmadzade, A., Mohammad-Pour, S., Morovatdar, N., Pourali, G., Zafari, N., Abbafati, C., Cattaruzza, M. S., Abbas, J., Phillips, M. R., Abbasgholizadeh, R., Emamverdi, M., Friedman, J., Abbasi, M. A., Daneshvar, S., Dashti, M., Ghasemzadeh, A., Mirza-Aghazadeh-Attari, M., Doshmangir, L., Ghafourifard, M., Lotfi, M., Hosseini, M., Jadidi-Niaragh, F., Kalankesh, L. R., Karimi, S., Mohammad-Alizadeh-Charandabi, S., Khalafi, M., Mirghafourvand, M., Mirinezhad, S., Heris, R. M., Mousavi, S., Kafil, H. S., Abbasian, M., Momenzadeh, K., Santos, F. C. D., Carr, S., Chi, G., Elgendy, I. Y., Feroze, A. H., Kempen, J. H., Kubeisy, C. M., Li, Z., Rohloff, P., Liu, X., Natto, Z. S., Olanipekun, T. O., Pigeolet, M., Pradhan, P. M. S., Zweck, E., Sharfaei, S., Sheikh, A., Abtahi, D., Salimi, S., Shakeri, A., Tajbakhsh, A., Aghamiri, S., Ahmadzade, M., Hashemi, M. B., Ajami, M., Asgary, S., Ghasemi, M., Hassanian-Moghaddam, H., Kolahi, A., Nikoobar, A., Heidari-Foroozan, M., Montazeri, F., Nejadghaderi, S., Rahmani, S., Ziaeefar, P., Hesami, H., Zahir, M., Jahankhani, K., Rasouli-Saravani, A., Jahanmehr, N., Kashani, H. K., Nasiri, M., Raee, P., Rezaee, M., Safi, S., Shool, S., Tabatabai, S., ElHafeez, S. A., Tantawi, M. E., Elmeligy, O. A. A., Ghazy, R. M., Talaat, I. M., Abdelmasseh, M., Sanabria, J., Abd-Elsalam, S., Abdelwahab, A., Abdollahi, M., Abolhassani, H., Rezaei, N., Saghazadeh, A., Ala, M., Noroozi, N., Bahri, R. A., Khatami, F., Ayyoubzadeh, S., Azadnajafabad, S., Keykhaei, M., Momtazmanesh, S., Mousavi, P., Behnoush, A., Farrokhpour, H., Karimi, H., Khalaji, A., Khanmohammadi, S., Mayeli, M., Mohammadi, S., Eskandarieh, S., Sahraian, M., Fahimi, S., Malekzadeh, R., Mansouri, V., Sepanlou, S. G., Ghassemi, F., Haddadi, M., Kazemian, S., Khadembashiri, M., Khamesipour, F., Khavandegar, A., Khormali, M., Salamati, P., Kompani, F., Larijani, B., Mirdamadi, N., Seyedi, S., Malazy, O. T., Mahmoudi, E., Rashedi, S., Rad, E. M., Mansournia, M., Nasab, E. M., Mohammadshahi, M., Mostafavi, H., SeyedAlinaghi, S., Shafie, M., Shahbandi, A., Vahdani, A. M., Sharifan, A., Shirkoohi, R., Sohrabi, H., Tavangar, S., Heidari-Soureshjani, R., Abdoun, M., Abdullahi, A., Awotidebe, A. W., Borodo, S. B., Gadanya, M. A., Ladan, M., Ali, M. U., Tyrovolas, S., Abdurehman, A. M., Debele, A. T., Getachew, T., Gudeta, M. D., Misgana, T., Sertsu, A., Abebe, M., Ayele, G. M., Afework, A., Lerango, T. L., Tebeje, T. M., Sibhat, M. M., Tesfaye, S. H., Abedi, A., Gholamrezanezhad, A., Salehi, S., Athari, S., Hanifi, N., Abegaz, T. M., Kifle, Z. D., Zuñiga, R. A. A., Abhilash, E. S., Abiodun, O. O., Aboagye, R. G., Amu, H., Ayanore, M. A., Dowou, R. K., Immurana, M., Klu, D., Orish, V. N., Carrero, J. J., Cederroth, C. R., Deuba, K., Laflamme, L., Fereshtehnejad, S., Kauppila, J. H., Abouzid, M., Abreu, L. G., Malta, D. C., Prates, E. J. S., Nascimento, B. R., Abrha, W. A., Weldemariam, A. H., Girmay, A., Abrigo, M. R. M., Rumeileh, S. A., Abu-Rmeileh, N. M., Aburuz, S., Ahmed, L. A., Alam, Z., Elbarazi, I., Grivna, M., Nauman, J., Khan, G., Khan, M. A., Zaki, N., Ahmad, M. M., Abu-Zaid, A., Temsah, R. M. H., Zand, R., Acuna, J. M., Gautam, P., Chowdhury, R., Adair, T., Jiang, H., Babu, A. S., Borschmann, R., Meretoja, A., Wijeratne, T., Addo, I. Y., Okeke, S. R., Dai, Z., Xu, X., Huda, M., Mitchell, P. B., Peden, A. E., Resnikoff, S., Sharma, S., Si, Y., Sitas, F., Ye, P., Adebayo, O. M., Aladelusi, T. O., Salami, A. A., Ilesanmi, O. S., Owolabi, M. O., Adegboye, O. A., Adekanmbi, V., AlBataineh, M. T., Almahmeed, W., Aden, B., Adepoju, A. V., Adetunji, C. O., Adeyeoluwa, T. E., Oyeyemi, I. T., Oyeyemi, O. T., Udoakang, A. J., Adeyomoye, O. I., Anuoluwa, I. A., Bello, O. O., Oluwafemi, Y. D., Ekundayo, T. C., Idowu, O. O., Oluwatunase, G. O., Afolabi, A. A., Ekholuenetale, M., Fagbamigbe, A. F., Olufadewa, I. I., Ibitoye, S. E., Okekunle, A. P., Adha, R., Adikusuma, W., Adibi, A., Chen, M., Hossain, M., Rasali, D. P., Pashaei, A., Adnani, Q. E. S., Postma, M. J., Adra, S., Barqawi, H. J., Dash, N. R., Halwani, R., Maghazachi, A. A., Saber-Ayad, M. M., Sharif-Askari, N. S., Ahmad, F., Saddik, B., Saleh, M. A., Alzoubi, K. H., Omar, H. A., Arumugam, A., Bustanji, Y., Elemam, N. M., Faris, M. E. M., Karim, A., Qaisar, R., Semreen, M. H., Soliman, S. S. M., Altirkawi, K. A., Afraz, A., Ilaghi, M., Nematollahi, M., Afyouni, S., Amindarolzarbi, A., Zandieh, G. G. Z., Columbus, A., Kamireddy, A., Shafaat, O., Kazemi, F., Vervoort, D., Zhang, H., Jamshidi, E., Afzal, S., Agasthi, P., Agodi, A., Barchitta, M., D'Amico, E., Maugeri, A., Veroux, M., Biondi, A., Isola, G., Vacante, M., Falzone, L., Libra, M., Agyemang-Duah, W., Nikpoor, A., Ahinkorah, B. O., Demant, D., Ahmad, A., Mustafa, G., Pathan, A. R., Tabish, M., Ahmad, D., Bagheri, N., Burns, R. A., Cherbuin, N., Ahmad, T., Ahmadi, K., Saxena, S., Beaney, T., Palladino, R., Rawaf, S., Mossialos, E., Rawaf, D. L., Ahmed, A., Siddig, E. E., Ahmed, H., Ahmed, M. B., Shiferaw, D., Ashemo, M. Y., Gerema, U., Getachew, M. E., Bayileyegn, N. S., Mohamed, A. I., Eshetie, T. C., Tiruye, T. Y., Ahmed, S., Ali, H., Bodunrin, A. O., Tumurkhuu, M., Tung, K., Ubah, C. S., Aruleba, R. T., Aji, B., Ajumobi, O., Akalu, G. T., Beyene, H. B., Deribe, K., Ijo, D., Kassaw, N. A., Akara, E., Akinosoglou, K., Akkala, S., Asaad, M., Hassan, A. M., Bleyer, A., Akyirem, S., Bell, M. L., Song, Y., Etaee, F., Goldust, M., Li, W., Pawar, S., Hamad, H. A., Sathian, B., Hasan, S. A., Homsi, A. A., Almidani, O., Göbölös, L., Qadire, M. A., AL-Ahdal, T. M. A., Chen, S., Moazen, B., Alalalmeh, S. O., Hegazi, O. E., Shahwan, M. J., Shamsi, M. A., Zyoud, S. H., Al-Aly, Z., Wang, C., Alam, K., Alam, M., Al-Amer, R. M., Naik, G. R., Alanzi, T. M., Bah, S., Menezes, R. G., Alanezi, F. M., Albashtawy, M., Aldridge, R. W., Chung, S., Hossain, S., Kim, J., Kivimäki, M., Sunkersing, D., Umar, T., Zumla, A., Alemi, S., Al-Eyadhy, A., Temsah, M., Alhabib, K. F., ElGohary, G. M. T., Meo, S. A., Al-Gheethi, A. A. S., Kiross, G. T., Alhalaiqa, F. A. N., Al-Maweri, S. A. A., Alomari, M. A., Mohammed, M., Al-Hanawi, M. K., Binmadi, N., Malik, A. A., Samargandy, S., Ali, A., Khan, I., Sawyer, S. M., Ali, B. A., Ali, R., Ali, S. S., Ali, Z., Samakkhah, S. A., Alicandro, G., Alif, S. M., Maharjan, P., Rai, P., Hasan, M., Thapa, R., Thrift, A. G., Aligol, M., Alimi, R., Aliyi, A. A., Jema, A., Al-Jumaily, A., Hankey, G. J., Kujan, O., Mansour, A., Aljunid, S. M., Al-Sabah, S. K., Al-Marwani, S., Almazan, J. U., Poddighe, D., Al-Mekhlafi, H. M., Ariffin, H., Lim, L., Bandyopadhyay, S., Basnyat, B., Maude, R. J., Bennett, D. A., Browne, A. J., Dolecek, C., Dunachie, S. J., Newton, C. R. J., Rodriguez, J. A. B., Kheirallah, K. A., Alonso, N., Bensenor, I. M., Brunoni, A. R., Castaldelli-Maia, J., Peres, M. F. P., Wang, Y., Alqahtani, J. S., Alqutaibi, A., Altaf, A., Alvi, F. J., Nargus, S., Arooj, M., Latif, M., Shahid, S., Shahid, W., Ashraf, M., Riaz, M. A., Al-Tawfiq, J. A., Alwafi, H., Rehman, F., Al-Worafi, Y. M., Aly, H., Ali, A. H., Amare, A., Gill, T. K., Yadav, L., Noubiap, J., Opio, J., Mengesha, E. W., Ameyaw, E. K., Amhare, A., Lin, S., Amin, T. T., Elhabashy, H. R., Hassan, A., Dehkordi, J. A., Kabir, H., Amiri, S., Amugsi, D. A., Wado, Y. D., Amzat, J., Bello, M. B., Shittu, A., Aruleba, I. T., Ancuceanu, R., Andrei, C., Florin, B. T., Negoi, I., Serban, D., Hostiuc, M., Hostiuc, S., Matei, C. N., Negoi, R. I., Anderlini, D., Begum, T., Kanmiki, E., Maravilla, J. C., Khan, A., Moni, M., Lalloo, R., McGrath, J. J., Veerman, L. J., Andrade, P. P., Busse, R., Mohammed, S., Andrei, T., Herteliu, C., Mirica, A., Otoiu, A., Petcu, I., Dima, A., Stefan, S., Angappan, D., Anil, A., Charan, J., Shamim, M., Singh, S., Varthya, S. B., Baskaran, P., Bhardwaj, P., Bhardwaj, N., Dixit, S. G., Krishna, H., Nayyar, A. K., Choudhary, R., Dixit, A., Misra, S., Mittal, M., Saravanan, A., Singh, M., Ram, P., Anjum, A., Antriyandarti, E., Anwar, S., Anyasodor, A. E., Appiah, S., Boampong, M. S., Aqeel, M., Arabloo, J., Eghdami, S., Panahi, P., Kabir, A., Salahi, S., Behnagh, A. K., Kasraei, H., Khodadoust, E., Latifinaibin, K., Moradi-Lakeh, M., Toroudi, H. P., Sarveazad, A., Zahedi, M., Moradi, M., Arab-Zozani, M., Ghalibaf, A. M., Rajabpour-Sanati, A., Arafat, M., Araújo, A. M., Belo, L., Carvalho, F., Costa, V. M., da Silva, D. D., Silva, J. P., Carvalho, M., Cruz-Martins, N., Freitas, A., Vieira, R. J., Pinheiro, M., Ribeiro, A., Aremu, A., Odetokun, I. A., Aripov, T., Armocida, B., Unim, B., Sabbatucci, M., Artamonov, A. A., Artanti, K. D., Efendi, F., Purnobasuki, H., Wulandari, R. D., Arulappan, J., Chavula, M. P., Edvardsson, D., Orru, H., Fattahi, H., Asika, M. O., Onwujekwe, O. E., Atout, M. M. W., Atreya, A., Attia, S., Aujayeb, A., Avan, A., Hachinski, V., Stranges, S., Bolarinwa, O. A., Ginindza, T. G., Ogunsakin, R. E., Quintanilla, B. A., Rahman, M., Ayuso-Mateos, J. L., Ortiz, A., Soriano, J. B., Catalá-López, F., Aziz, S., Azzam, A. Y., Babashahi, M., Bayati, M., Kouhanjani, M. F., Fazeli, P., Karajizadeh, M., Ghahramani, S., Sarikhani, Y., Shahabi, S., Iravanpour, F., Jafarinia, M., Oliaee, R. T., Ravangard, R., Razeghian-Jahromi, I., Roshanzamir, S., Mansoori, Y., Bakkannavar, S. M., Nayak, V. C., Holla, R., Kamath, A., Rao, M., Ligade, V. S., Rao, C. R., Shetty, R. S., Rao, I., Reshmi, B., Badar, M., Badawi, A., Bhutta, Z. A., Chattu, V., Malhotra, A. K., Mostofinejad, A., Shakil, H., Badiye, A. D., Bansal, H., Kapoor, N., Baghdadi, S., Bagherieh, S., Fatehizadeh, A., Mehrabani-Zeinabad, K., Sadeghi, M., Mirmosayyeb, O., Saber, K., Shafaat, A., Bahadorikhalili, S., Bai, J., Yu, C., Bai, R., Baker, J. L., Bako, A. T., Makram, O. M., Balakrishnan, S., Balogun, S. A., Singh, A., Tian, J., Jatau, A., Baltatu, O. C., Baltatu, O., Campos, L. A., Bam, K., Olaiya, M. T., Bhandari, D., Dalli, L. L., Banach, M., Banik, B., Banik, P. C., Barati, S., Saeedi, M., Bardhan, M., Barker-Collo, S. L., Beyene, K. A., Barone-Adesi, F., Barr, R. D., Kurmi, O. P., Mannan, F., Olagunju, A. T., Barrero, L. H., Basharat, Z., Bashir, A. I. J., Bashiru, H. A., Folayan, M. O., Bassat, Q., Basso, J. D., Silva, S., Rodrigues, M., Basu, S., Batra, K., Batra, R., Sharma, M., Baune, B. T., Bedi, N., Ghailan, K. Y., Khan, M., Halboub, E. S., Shanawaz, M., Sayeed, A., Siraj, M., Behboudi, E., Soleimani, H., Beiranvand, M., Ramirez, D. F. B., Malagón-Rojas, J. N., Belgaumi, U. I., Bello, A. K., Ebenezer, O., Eboreime, E., Umair, M., Beloukas, A., Lunevicius, R., Bendak, S., Benzian, H., Friedman, S. D., Peprah, E. K., Berezvai, Z., Berman, A. E., Bermudez, A. C., Loreche, A., Liu, S., Mohamed, M. F. H., Bettencourt, P. J. G., Bhagat, D. S., Bhagavathula, A. S., Bhala, N., Dehbandi, R., Glasbey, J. C., Bhalla, A., Marasini, B. P., Paudel, U., Poudel, L., Bhardwaj, P. V., Bhargava, A., Kahe, F., Bhaskar, S., Bhat, V., Bhatti, G. K., Kalra, S., Bhatti, J. S., Senapati, S., Bhatti, M. S., Bhatti, R., Das, J. K., Bikbov, B., Bintoro, B., Bisulli, F., Golinelli, D., Guicciardi, S., Lenzi, J., Mazzotti, A., Muccioli, L., Sanmarchi, F., Violante, F. S., Biswas, A., Dhali, A., Biswas, R., Chen, L., Driscoll, T. R., Tang, H. K., Islam, S., Kandel, H., You, Y., Leigh, J., Singh, B. B., Visontay, R., Bitaraf, S., Kaydi, N., Eini, E., Khafaie, M. A., Sadeghian, S., Bjørge, T., Dadras, O., Wojewodzic, M. W., Bodolica, V., Bonny, A., Bora, K., Basara, B. B., Francis, K. L., Kerr, J. A., Carvajal, A. B., Bouaoud, S., Ouyahia, A., Boudalia, S., Lanfranchi, F., Bragazzi, N. L., Braithwaite, D., Ding, D. D., Karanth, S. D., Naghavi, P., Brenner, H., Britton, G., Bulamu, N. B., Bulto, L. N., Foley, K. M., Jemere, D., Kaambwa, B., Mpundu-Kaambwa, C., Buonsenso, D., Villani, L., Nagaraja, S. B., Butt, Z. A., Cai, T., Calina, D., Cámera, L. A., Campos-Nonato, I. R., Denova-Gutiérrez, E., Ortega-Altamirano, D. V., Rios-Blancas, M., Pando-Robles, V., Cao, C., Cardenas, C. A., Cárdenas, R., Carreras, G., Carugno, A., Castañeda-Orjuela, C. A., Castelpietra, G., Catapano, A. L., Damiani, G., Vecchia, C. L., Caye, A., Duncan, B. B., Schmidt, M. I., Hugo, F. N., Cembranel, F., Cenderadewi, M., Emeto, T. I., Obamiro, K. O., Cerin, E., Poudel, G. R., Guo, C., Sarkar, C., Yip, P., Cevik, M., Chacón-Uscamaita, P. R., Chirinos-Caceres, J. L., Chakraborty, C., Chan, J., Chang, C., Douiri, A., Wafa, H. A., Hbid, Y., Mazidi, M., Urso, D., Charalampous, P., Volovici, V., Chatzimavridou-Grigoriadou, V., Johnson, O., Mathioudakis, A. G., Mughal, F., Cheema, H. A., Chen, A., Chen, H., Zhu, Z., Chew, D. S., Tonelli, M., Yang, L., Chitheer, A., Cho, S. J., Ebrahimi, A., Nguyen, D. H., Cho, W. C. S., Chong, B., Ma, S., Ramazanu, S., Tan, K., Venketasubramanian, N., Chopra, H., Mini, G., Tovani-Palone, M. R., Pantazopoulos, I., Pilgrim, T., Stortecky, S., Chu, D., Chukwu, I. S., Cini, K. I., Clark, C. C. T., Conde, J., Conti, S., Cortesi, P. A., Fornari, C., Mantovani, L. G., Ferrara, P., Cowden, R. G., Criqui, M. H., Cullen, P., Jarlais, D. C. D., Gunturu, S., Dadana, S., Dalal, Koustuv, Kurmanova, A., Guha, A., Qattea, I., Darwesh, A. M., Hosseinzadeh, M., Das, S., Dávila-Cervantes, C. A., Davletov, K., Leo, D. D., Delgado-Enciso, I., Delgado-Ortiz, L., Morawska, L., Demessa, B. H., Demetriades, A. K., Eze, U. A., Simpson, C. 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Abstract: Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, ant
Published: 2024
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5. Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Author: Schumacher, A, Kyu, H, Aali, A, Abbafati, C, Abbas, J, Abbasgholizadeh, R, Abbasi, M, Abbasian, M, Abd ElHafeez, S, Abdelmasseh, M, Abd-Elsalam, S, Abdelwahab, A, Abdollahi, M, Abdoun, M, Abdullahi, A, Abdurehman, A, Abebe, M, Abedi, A, Abegaz, T, Abeldaño Zuñiga, R, Abhilash, E, Abiodun, O, Aboagye, R, Abolhassani, H, Abouzid, M, Abreu, L, Abrha, W, Abrigo, M, Abtahi, D, Abu Rumeileh, S, Abu-Rmeileh, N, Aburuz, S, Abu-Zaid, A, Acuna, J, Adair, T, Addo, I, Adebayo, O, Adegboye, O, Adekanmbi, V, Aden, B, Adepoju, A, Adetunji, C, Adeyeoluwa, T, Adeyomoye, O, Adha, R, Adibi, A, Adikusuma, W, Adnani, Q, Adra, S, Afework, A, Afolabi, A, Afraz, A, Afyouni, S, Afzal, S, Agasthi, P, Aghamiri, S, Agodi, A, Agyemang-Duah, W, Ahinkorah, B, Ahmad, A, Ahmad, D, Ahmad, F, Ahmad, M, Ahmad, T, Ahmadi, K, Ahmadzade, A, Ahmadzade, M, Ahmed, A, Ahmed, H, Ahmed, L, Ahmed, M, Ahmed, S, Ajami, M, Aji, B, Ajumobi, O, Akalu, G, Akara, E, Akinosoglou, K, Akkala, S, Akyirem, S, Al Hamad, H, Al Hasan, 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Shubha, Jeganathan, Jayakumar, Jema, Alelign Tasew, Jemere, Digisie Mequanint, Jeong, Wonjeong, Jha, Anil K, Jha, Ravi Prakash, Ji, John S, Jiang, Heng, Jin, Yingzhao, Jin, Yinzi, Johnson, Olatunji, Jomehzadeh, Nabi, Jones, Darwin Phan, Joo, Tamas, Joseph, Abel, Joseph, Nitin, Joshua, Charity Ehimwenma, Jozwiak, Jacek Jerzy, Jürisson, Mikk, Kaambwa, Billingsley, Kabir, Ali, Kabir, Hannaneh, Kabir, Zubair, Kadashetti, Vidya, Kahe, Farima, Kakodkar, Pradnya Vishal, Kalani, Rizwan, Kalankesh, Leila R, Kaliyadan, Feroze, Kalra, Sanjay, Kamath, Ashwin, Kamireddy, Arun, Kanagasabai, Thanigaivelan, Kandel, Himal, Kanmiki, Edmund Wedam, Kanmodi, Kehinde Kazeem, Kantar, Rami S, Kapoor, Neeti, Karajizadeh, Mehrdad, Karami Matin, Behzad, Karanth, Shama D, Karaye, Ibraheem M, Karim, Asima, Karimi, Hanie, Karimi, Salah Eddin, Karimi Behnagh, Arman, Karkhah, Samad, Karna, Ajit K, Kashoo, Faizan Zaffar, Kasraei, Hengameh, Kassaw, Nigussie Assefa, Kassebaum, Nicholas J, Kassel, Molly B, Katamreddy, 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Published: 2024

6. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Author: Naghavi, M, Ong, K, Aali, A, Ababneh, H, Abate, Y, Abbafati, C, Abbasgholizadeh, R, Abbasian, M, Abbasi-Kangevari, M, Abbastabar, H, Abd ElHafeez, S, Abdelmasseh, M, Abd-Elsalam, S, Abdelwahab, A, Abdollahi, M, Abdollahifar, M, Abdoun, M, Abdulah, D, Abdullahi, A, Abebe, M, Abebe, S, Abedi, A, Abegaz, K, Abhilash, E, Abidi, H, Abiodun, O, Aboagye, R, Abolhassani, H, Abolmaali, M, Abouzid, M, Aboye, G, Abreu, L, Abrha, W, Abtahi, D, Abu Rumeileh, S, Abualruz, H, Abubakar, B, Abu-Gharbieh, E, Abu-Rmeileh, N, Aburuz, S, Abu-Zaid, A, Accrombessi, M, Adal, T, Adamu, A, Addo, I, Addolorato, G, Adebiyi, A, Adekanmbi, V, Adepoju, A, Adetunji, C, Adetunji, J, Adeyeoluwa, T, Adeyinka, D, Adeyomoye, O, Admass, B, Adnani, Q, Adra, S, Afolabi, A, Afzal, M, Afzal, S, Agampodi, S, Agasthi, P, Aggarwal, M, Aghamiri, S, Agide, F, Agodi, A, Agrawal, A, Agyemang-Duah, W, Ahinkorah, B, Ahmad, A, Ahmad, D, Ahmad, F, Ahmad, M, Ahmad, S, Ahmad, T, Ahmadi, K, Ahmadzade, A, Ahmed, A, Ahmed, H, Ahmed, L, Ahmed, M, Ahmed, S, Ajami, M, Aji, B, Akara, E, Akbarialiabad, H, Akinosoglou, K, Akinyemiju, T, Akkaif, M, Akyirem, S, Al Hamad, H, Al Hasan, S, Alahdab, F, Alalalmeh, S, Alalwan, T, Al-Aly, Z, Alam, K, Alam, M, Alam, N, Al-amer, R, Alanezi, F, Alanzi, T, Al-Azzam, S, Albakri, A, Albashtawy, M, Albataineh, M, Alcalde-Rabanal, J, Aldawsari, K, Aldhaleei, W, Aldridge, R, Alema, H, Alemayohu, M, Alemi, S, Alemu, Y, Al-Gheethi, A, Alhabib, K, Alhalaiqa, F, Al-Hanawi, M, Ali, A, Ali, L, Ali, M, Ali, R, Ali, S, Alicandro, G, Alif, S, Alikhani, R, Alimohamadi, Y, Aliyi, A, Aljasir, M, Aljunid, S, Alla, F, Allebeck, P, Al-Marwani, S, Al-Maweri, S, Almazan, J, Al-Mekhlafi, H, Almidani, L, Almidani, O, Alomari, M, Al-Omari, B, Alonso, J, Alqahtani, J, Alqalyoobi, S, Alqutaibi, A, Al-Sabah, S, Altaany, Z, Altaf, A, Al-Tawfiq, J, Altirkawi, K, Aluh, D, Alvis-Guzman, N, Alwafi, H, Al-Worafi, Y, Aly, H, Aly, S, Alzoubi, K, Amani, R, Amare, A, Amegbor, P, Ameyaw, E, Amin, T, Amindarolzarbi, A, 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Francesca, Santomauro, Damian Francesco, Santos, Itamar S, Santric-Milicevic, Milena M, Sao Jose, Bruno Piassi, Sarasmita, Made Ary, Saraswathy, Sivan Yegnanarayana Iyer, Saravanan, Aswini, Saravi, Babak, Sarikhani, Yaser, Sarkar, Tanmay, Sarmiento-Suárez, Rodrigo, Sarode, Gargi Sachin, Sarode, Sachin C, Sarveazad, Arash, Sathian, Brijesh, Sathish, Thirunavukkarasu, Satpathy, Maheswar, Sayeed, Abu, Sayeed, Md Abu, Saylan, Mete, Sayyah, Mehdi, Scarmeas, Nikolaos, Schaarschmidt, Benedikt Michael, Schlaich, Markus P, Schlee, Winfried, Schmidt, Maria Inês, Schneider, Ione Jayce Ceola, Schuermans, Art, Schumacher, Austin E, Schutte, Aletta Elisabeth, Schwarzinger, Michaël, Schwebel, David C, Schwendicke, Falk, Šekerija, Mario, Selvaraj, Siddharthan, Senapati, Sabyasachi, Senthilkumaran, Subramanian, Sepanlou, Sadaf G, Serban, Dragos, Sethi, Yashendra, Sha, Feng, Shabany, Maryam, Shafaat, Amir, Shafie, Mahan, Shah, Nilay S, Shah, Pritik A, Shah, Syed Mahboob, Shahabi, Saeed, Shahbandi, Ataollah, Shahid, Izza, Shahid, Samiah, Shahid, Wajeehah, Shahsavari, Hamid R, Shahwan, Moyad Jamal, Shaikh, Ahmed, Shaikh, Masood Ali, Shakeri, Alireza, Shalash, Ali S, Sham, Sunder, Shamim, Muhammad Aaqib, Shams-Beyranvand, Mehran, Shamshad, Hina, Shamsi, Mohammad Anas, Shanawaz, Mohd, Shankar, Abhishek, Sharfaei, Sadaf, Sharifan, Amin, Sharifi-Rad, Javad, Sharma, Rajesh, Sharma, Saurab, Sharma, Ujjawal, Sharma, Vishal, Shastry, Rajesh P, Shavandi, Amin, Shayan, Maryam, Shehabeldine, Amr Mohamed Elsayed, Sheikh, Aziz, Sheikhi, Rahim Ali, Shen, Jiabin, Shetty, Adithi, Shetty, B Suresh Kumar, Shetty, Pavanchand H, Shi, Peilin, Shibuya, Kenji, Shiferaw, Desalegn, Shigematsu, Mika, Shin, Min-Jeong, Shin, Youn Ho, Shiri, Rahman, Shirkoohi, Reza, Shitaye, Nebiyu Aniley, Shittu, Aminu, Shiue, Ivy, Shivakumar, K M, Shivarov, Velizar, Shokraneh, Farhad, Shokri, Azad, Shool, Sina, Shorofi, Seyed Afshin, Shrestha, Sunil, Shuval, Kerem, Siddig, Emmanuel Edwar, Silva, João Pedro, Silva, Luís Manuel Lopes Rodrigues, Silva, Soraia, Simpson, Colin R, Singal, Anjali, Singh, Abhinav, Singh, Balbir Bagicha, Singh, Garima, Singh, Jasbir, Singh, Narinder Pal, Singh, Paramdeep, Singh, Surjit, Sinha, Dhirendra Narain, Sinto, Robert, Siraj, Md Shahjahan, Sirota, Sarah Brooke, Sitas, Freddy, Sivakumar, Shravan, Skryabin, Valentin Yurievich, Skryabina, Anna Aleksandrovna, Sleet, David A, Socea, Bogdan, Sokhan, Anton, Solanki, Ranjan, Solanki, Shipra, Soleimani, Hamidreza, Soliman, Sameh S M, Song, Suhang, Song, Yimeng, Sorensen, Reed J D, Soriano, Joan B, Soyiri, Ireneous N, Spartalis, Michael, Spearman, Sandra, Sreeramareddy, Chandrashekhar T, Srivastava, Vijay Kumar, Stanaway, Jeffrey D, Stanikzai, Muhammad Haroon, Stark, Benjamin A, Starnes, Joseph R, Starodubova, Antonina V, Stein, Caroline, Stein, Dan J, Steinbeis, Fridolin, Steiner, Caitlyn, Steinmetz, Jaimie D, Steiropoulos, Paschalis, Stevanović, Aleksandar, Stockfelt, Leo, Stokes, Mark A, Stortecky, Stefan, Subramaniyan, 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Pugazhenthan, Thankappan, Kavumpurathu Raman, Tharwat, Samar, Thayakaran, Rasiah, Thomas, Nihal, Thomas, Nikhil Kenny, Thomson, Azalea M, Thrift, Amanda G, Thum, Chern Choong Chern, Thygesen, Lau Caspar, Tian, Jing, Tichopad, Ales, Ticoalu, Jansje Henny Vera, Tillawi, Tala, Tiruye, Tenaw Yimer, Titova, Mariya Vladimirovna, Tonelli, Marcello, Topor-Madry, Roman, Toriola, Adetunji T, Torre, Anna E, Touvier, Mathilde, Tovani-Palone, Marcos Roberto, Tran, Jasmine T, Tran, Nghia Minh, Trico, Domenico, Tromans, Samuel Joseph, Truyen, Thien Tan Tri Tai, Tsatsakis, Aristidis, Tsegay, Guesh Mebrahtom, Tsermpini, Evangelia Eirini, Tumurkhuu, Munkhtuya, Tung, Kang, Tyrovolas, Stefanos, Uddin, Sayed Mohammad Nazim, Udoakang, Aniefiok John, Udoh, Arit, Ullah, Atta, Ullah, Irfan, Ullah, Saeed, Ullah, Sana, Umakanthan, Srikanth, Umeokonkwo, Chukwuma David, Unim, Brigid, Unnikrishnan, Bhaskaran, Unsworth, Carolyn Anne, Upadhyay, Era, Urso, Daniele, Usman, Jibrin Sammani, Vahabi, Seyed Mohammad, 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Taweewat, Wickramasinghe, Dakshitha Praneeth, Wickramasinghe, Nuwan Darshana, Wilandika, Angga, Wilkerson, Caroline, Willeit, Peter, Wilson, Shadrach, Wojewodzic, Marcin W, Woldegebreal, Demewoz H, Wolf, Axel Walter, Wolfe, Charles D A, Wondimagegene, Yohannes Addisu, Wong, Yen Jun, Wongsin, Utoomporn, Wu, Ai-Min, Wu, Chenkai, Wu, Felicia, Wu, Xinsheng, Wu, Zenghong, Xia, Juan, Xiao, Hong, Xie, Yang, Xu, Suowen, Xu, Wang-Dong, Xu, Xiaoyue, Xu, Yvonne Yiru, Yadollahpour, Ali, Yamagishi, Kazumasa, Yang, Danting, Yang, Lin, Yano, Yuichiro, Yao, Yao, Yaribeygi, Habib, Ye, Pengpeng, Yehualashet, Sisay Shewasinad, Yesiltepe, Metin, Yesuf, Subah Abderehim, Yezli, Saber, Yi, Siyan, Yigezu, Amanuel, Yiğit, Arzu, Yiğit, Vahit, Yip, Paul, Yismaw, Malede Berihun, Yismaw, Yazachew, Yon, Dong Keon, Yonemoto, Naohiro, Yoon, Seok-Jun, You, Yuyi, Younis, Mustafa Z, Yousefi, Zabihollah, Yu, Chuanhua, Yu, Yong, Yuh, Faith H, Zadey, Siddhesh, Zadnik, Vesna, Zafari, Nima, Zakham, Fathiah, Zaki, Nazar, Zaman, Sojib Bin, Zamora, Nelson, Zand, Ramin, Zangiabadian, Moein, Zar, Heather J, Zare, Iman, Zarrintan, Armin, Zeariya, Mohammed G M, Zeinali, Zahra, Zhang, Haijun, Zhang, Jianrong, Zhang, Jingya, Zhang, Liqun, Zhang, Yunquan, Zhang, Zhi-Jiang, Zhao, Hanqing, Zhong, Chenwen, Zhou, Juexiao, Zhu, Bin, Zhu, Lei, Ziafati, Makan, Zielińska, Magdalena, Zitoun, Osama A, Zoladl, Mohammad, Zou, Zhiyong, Zuhlke, Liesl J, Zumla, Alimuddin, Zweck, Elric, Zyoud, Samer H, Wool, Eve E, and Murray, Christopher J L
Published: 2024

7. Effectiveness of perampanel as the only add‐on: Retrospective, multicenter, observational real‐life study on epilepsy patients

Author: Gasparini S., Ferlazzo E., Neri S., Cianci V., Iudice A., Bisulli F., Bonanni P., Caggia E., D'Aniello A., Di Bonaventura C., Di Francesco J. C., Domina E., Dono F., Gambardella A., Marini C., Marrelli A., Matricardi S., Morano A., Paladin F., Renna R., Striano P., Pascarella A., Ascoli M., Aguglia U., PEROC Study Group, Gasparini S., Ferlazzo E., Neri S., Cianci V., Iudice A., Bisulli F., Bonanni P., Caggia E., D'Aniello A., Di Bonaventura C., Di Francesco J.C., Domina E., Dono F., Gambardella A., Marini C., Marrelli A., Matricardi S., Morano A., Paladin F., Renna R., Striano P., Pascarella A., Ascoli M., Aguglia U., and PEROC Study Group
Subjects: real-world, perampanel, Neurology, seizure freedom, early add-on, Neurology (clinical)
Abstract: Objective: Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add-on treatment. Methods: We performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add-on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency, and adverse events were recorded at 3, 6, and 12months after PER introduction. Subanalyses by early or late use of PER and by concomitant ASM were also conducted. Results: Five hundred and three patients were included (age 36.5 ± 19.9 years). Eighty-one percent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12months) according with efficacy measures. No major differences were observed in the subanalyses, although patients who used PER as early add-on, as compared with late add-on, more often reached early seizure freedom at 3-month follow-up (66% vs 53%, P=.05). Treatment-emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. Significance: This study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real-life conditions. We provide robust data about its effectiveness as only add-on treatment even in patients with a long-standing history of epilepsy and previously treated with many ASMs.
Published: 2022

8. The Prognostic Roles of Gender and O6-Methylguanine-DNA Methyltransferase Methylation Status in Glioblastoma Patients: The Female Power

Author: Baruzzi, A., Albani, F., Calbucci, F., D'Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, E., Biasini, C., Cavanna, L., Guidetti, D., Marcello, N., Pisanello, A., Cremonini, A.M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall'Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall'Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Faedi, M., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A.R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, M., Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M.R., Urbini, B., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E.M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., Franceschi, Enrico, Tosoni, Alicia, Minichillo, Santino, Depenni, Roberta, Paccapelo, Alexandro, Bartolini, Stefania, Michiara, Maria, Pavesi, Giacomo, Urbini, Benedetta, Crisi, Girolamo, Cavallo, Michele A., Tosatto, Luigino, Dazzi, Claudio, Biasini, Claudia, Pasini, Giuseppe, Balestrini, Damiano, Zanelli, Francesca, Ramponi, Vania, Fioravanti, Antonio, Giombelli, Ermanno, De Biase, Dario, Baruzzi, Agostino, and Brandes, Alba A.
Published: 2018
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9. Sleep-related hypermotor epilepsy: prevalence, impact and management strategies

Author: Menghi V, Bisulli F, Tinuper P, and Nobili L
Subjects: epilepsy, parasomnias, sleep-related hypermotor epilepsy, nocturnal frontal lobe epilepsy, epidemiology., Psychiatry, RC435-571, Neurophysiology and neuropsychology, QP351-495
Abstract: Veronica Menghi,1 Francesca Bisulli,2 Paolo Tinuper,2 Lino Nobili3,4 1Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 3“Claudio Munari” Center for Epilepsy Surgery, Niguarda Hospital, Milan, Italy; 4Department of Neuroscience (DINOGMI), IRCCS, Giannina Gaslini Institute, University of Genoa, Genoa, Italy Abstract: Sleep-related hypermotor epilepsy (SHE), previously called nocturnal frontal lobe epilepsy (NFLE), is a focal epilepsy characterized by asymmetric tonic/dystonic posturing and/or complex hyperkinetic seizures occurring mostly during sleep. SHE fulfills the definition of rare disease with an estimated minimum prevalence of 1.8/100,000 individuals, and it represents about 10% of drug-resistant surgical cases. Although SHE and autosomal-dominant SHE (ADSHE) have been considered benign epileptic conditions for a long time, emerging data have shed light on the severity of this disorder and some peculiar features can impact negatively on the quality of life of SHE patients. In fact, seizure frequency can be very high, resulting in nocturnal sleep fragmentation with possible diurnal consequences such as excessive sleepiness and fatigue. Moreover, recent studies, adopting a systematic neuropsychological assessment, have shown deficits in memory, executive functions and visuo-spatial abilities in almost half of SHE patients. Intellectual disabilities and psychiatric disorders have also been reported in some genetic forms. SHE may also exert a negative effect on health-related quality of life, especially in domains pertaining to a patient’s role in the family, social context and patient’s illness experience. Despite a good response to pharmacological treatment, especially with carbamazepine, 30% of SHE patients suffer from drug-resistant seizures. Finally, recent studies suggest a poor prognosis in a high percentage of SHE patients with a 20.4% cumulative probability of achieving terminal remission at 10 years from onset. For selected drug-resistant SHE patients, epilepsy surgery is the only treatment offering high probability of recovery, both for seizures and for epilepsy-related sleep alterations. Keywords: epilepsy, parasomnias, sleep-related hypermotor epilepsy, nocturnal frontal lobe epilepsy, epidemiology
Published: 2018

10. GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Author: Stevelink, R, Campbell, C, Chen, S, Abou-Khalil, B, Adesoji, OM, Afawi, Z, Amadori, E, Anderson, A, Anderson, J, Andrade, DM, Annesi, G, Auce, P, Avbersek, A, Bahlo, M, Baker, MD, Balagura, G, Balestrini, S, Barba, C, Barboza, K, Bartolomei, F, Bast, T, Baum, L, Baumgartner, T, Baykan, B, Bebek, N, Becker, AJ, Becker, F, Bennett, CA, Berghuis, B, Berkovic, SF, Beydoun, A, Bianchini, C, Bisulli, F, Blatt, I, Bobbili, DR, Borggraefe, I, Bosselmann, C, Braatz, V, Bradfield, JP, Brockmann, K, Brody, LC, Buono, RJ, Busch, RM, Caglayan, H, Campbell, E, Canafoglia, L, Canavati, C, Cascino, GD, Castellotti, B, Catarino, CB, Cavalleri, GL, Cerrato, F, Chassoux, F, Cherny, SS, Cheung, C-L, Chinthapalli, K, Chou, I-J, Chung, S-K, Churchhouse, C, Clark, PO, Cole, AJ, Compston, A, Coppola, A, Cosico, M, Cossette, P, Craig, JJ, Cusick, C, Daly, MJ, Davis, LK, de Haan, G-J, Delanty, N, Depondt, C, Derambure, P, Devinsky, O, Di Vito, L, Dlugos, DJ, Doccini, V, Doherty, CP, El-Naggar, H, Elger, CE, Ellis, CA, Eriksson, JG, Faucon, A, Feng, Y-CA, Ferguson, L, Ferraro, TN, Ferri, L, Feucht, M, Fitzgerald, M, Fonferko-Shadrach, B, Fortunato, F, Franceschetti, S, Franke, A, French, JA, Freri, E, Gagliardi, M, Gambardella, A, Geller, EB, Giangregorio, T, Gjerstad, L, Glauser, T, Goldberg, E, Goldman, A, Granata, T, Greenberg, DA, Guerrini, R, Gupta, N, Haas, KF, Hakonarson, H, Hallmann, K, Hassanin, E, Hegde, M, Heinzen, EL, Helbig, I, Hengsbach, C, Heyne, HO, Hirose, S, Hirsch, E, Hjalgrim, H, Howrigan, DP, Hucks, D, Hung, P-C, Iacomino, M, Imbach, LL, Inoue, Y, Ishii, A, Jamnadas-Khoda, J, Jehi, L, Johnson, MR, Kalviainen, R, Kamatani, Y, Kanaan, M, Kanai, M, Kantanen, A-M, Kara, B, Kariuki, SM, Kasperaviciute, D, Trenite, DK-N, Kato, M, Kegele, J, Kesim, Y, Khoueiry-Zgheib, N, King, C, Kirsch, HE, Klein, KM, Kluger, G, Knake, S, Knowlton, RC, Koeleman, BPC, Korczyn, AD, Koupparis, A, Kousiappa, I, Krause, R, Krenn, M, Krestel, H, Krey, I, Kunz, WS, Kurki, MI, Kurlemann, G, Kuzniecky, R, Kwan, P, Labate, A, Lacey, A, Lal, D, Landoulsi, Z, Lau, Y-L, Lauxmann, S, Leech, SL, Lehesjoki, A-E, Lemke, JR, Lerche, H, Lesca, G, Leu, C, Lewin, N, Lewis-Smith, D, Li, GH-Y, Li, QS, Licchetta, L, Lin, K-L, Lindhout, D, Linnankivi, T, Lopes-Cendes, I, Lowenstein, DH, Lui, CHT, Madia, F, Magnusson, S, Marson, AG, May, P, McGraw, CM, Mei, D, Mills, JL, Minardi, R, Mirza, N, Moller, RS, Molloy, AM, Montomoli, M, Mostacci, B, Muccioli, L, Muhle, H, Mueller-Schlueter, K, Najm, IM, Nasreddine, W, Neale, BM, Neubauer, B, Newton, CRJC, Noethen, MM, Nothnagel, M, Nuernberg, P, O'Brien, TJ, Okada, Y, Olafsson, E, Oliver, KL, Ozkara, C, Palotie, A, Pangilinan, F, Papacostas, SS, Parrini, E, Pato, CN, Pato, MT, Pendziwiat, M, Petrovski, S, Pickrell, WO, Pinsky, R, Pippucci, T, Poduri, A, Pondrelli, F, Powell, RHW, Privitera, M, Rademacher, A, Radtke, R, Ragona, F, Rau, S, Rees, MI, Regan, BM, Reif, PS, Rhelms, S, Riva, A, Rosenow, F, Ryvlin, P, Saarela, A, Sadleir, LG, Sander, JW, Sander, T, Scala, M, Scattergood, T, Schachter, SC, Schankin, CJ, Scheffer, IE, Schmitz, B, Schoch, S, Schubert-Bast, S, Schulze-Bonhage, A, Scudieri, P, Sham, P, Sheidley, BR, Shih, JJ, Sills, GJ, Sisodiya, SM, Smith, MC, Smith, PE, Sonsma, ACM, Speed, D, Sperling, MR, Stefansson, H, Stefansson, K, Steinhoff, BJ, Stephani, U, Stewart, WC, Stipa, C, Striano, P, Stroink, H, Strzelczyk, A, Surges, R, Suzuki, T, Tan, KM, Taneja, RS, Tanteles, GA, Tauboll, E, Thio, LL, Thomas, GN, Thomas, RH, Timonen, O, Tinuper, P, Todaro, M, Topaloglu, P, Tozzi, R, Tsai, M-H, Tumiene, B, Turkdogan, D, Unnsteinsdottir, U, Utkus, A, Vaidiswaran, P, Valton, L, van Baalen, A, Vetro, A, Vining, EPG, Visscher, F, von Brauchitsch, S, von Wrede, R, Wagner, RG, Weber, YG, Weckhuysen, S, Weisenberg, J, Weller, M, Widdess-Walsh, P, Wolff, M, Wolking, S, Wu, D, Yamakawa, K, Yang, W, Yapici, Z, Yucesan, E, Zagaglia, S, Zahnert, F, Zara, F, Zhou, W, Zimprich, F, Zsurka, G, Ali, QZ, Stevelink, R, Campbell, C, Chen, S, Abou-Khalil, B, Adesoji, OM, Afawi, Z, Amadori, E, Anderson, A, Anderson, J, Andrade, DM, Annesi, G, Auce, P, Avbersek, A, Bahlo, M, Baker, MD, Balagura, G, Balestrini, S, Barba, C, Barboza, K, Bartolomei, F, Bast, T, Baum, L, Baumgartner, T, Baykan, B, Bebek, N, Becker, AJ, Becker, F, Bennett, CA, Berghuis, B, Berkovic, SF, Beydoun, A, Bianchini, C, Bisulli, F, Blatt, I, Bobbili, DR, Borggraefe, I, Bosselmann, C, Braatz, V, Bradfield, JP, Brockmann, K, Brody, LC, Buono, RJ, Busch, RM, Caglayan, H, Campbell, E, Canafoglia, L, Canavati, C, Cascino, GD, Castellotti, B, Catarino, CB, Cavalleri, GL, Cerrato, F, Chassoux, F, Cherny, SS, Cheung, C-L, Chinthapalli, K, Chou, I-J, Chung, S-K, Churchhouse, C, Clark, PO, Cole, AJ, Compston, A, Coppola, A, Cosico, M, Cossette, P, Craig, JJ, Cusick, C, Daly, MJ, Davis, LK, de Haan, G-J, Delanty, N, Depondt, C, Derambure, P, Devinsky, O, Di Vito, L, Dlugos, DJ, Doccini, V, Doherty, CP, El-Naggar, H, Elger, CE, Ellis, CA, Eriksson, JG, Faucon, A, Feng, Y-CA, Ferguson, L, Ferraro, TN, Ferri, L, Feucht, M, Fitzgerald, M, Fonferko-Shadrach, B, Fortunato, F, Franceschetti, S, Franke, A, French, JA, Freri, E, Gagliardi, M, Gambardella, A, Geller, EB, Giangregorio, T, Gjerstad, L, Glauser, T, Goldberg, E, Goldman, A, Granata, T, Greenberg, DA, Guerrini, R, Gupta, N, Haas, KF, Hakonarson, H, Hallmann, K, Hassanin, E, Hegde, M, Heinzen, EL, Helbig, I, Hengsbach, C, Heyne, HO, Hirose, S, Hirsch, E, Hjalgrim, H, Howrigan, DP, Hucks, D, Hung, P-C, Iacomino, M, Imbach, LL, Inoue, Y, Ishii, A, Jamnadas-Khoda, J, Jehi, L, Johnson, MR, Kalviainen, R, Kamatani, Y, Kanaan, M, Kanai, M, Kantanen, A-M, Kara, B, Kariuki, SM, Kasperaviciute, D, Trenite, DK-N, Kato, M, Kegele, J, Kesim, Y, Khoueiry-Zgheib, N, King, C, Kirsch, HE, Klein, KM, Kluger, G, Knake, S, Knowlton, RC, Koeleman, BPC, Korczyn, AD, Koupparis, A, Kousiappa, I, Krause, R, Krenn, M, Krestel, H, Krey, I, Kunz, WS, Kurki, MI, Kurlemann, G, Kuzniecky, R, Kwan, P, Labate, A, Lacey, A, Lal, D, Landoulsi, Z, Lau, Y-L, Lauxmann, S, Leech, SL, Lehesjoki, A-E, Lemke, JR, Lerche, H, Lesca, G, Leu, C, Lewin, N, Lewis-Smith, D, Li, GH-Y, Li, QS, Licchetta, L, Lin, K-L, Lindhout, D, Linnankivi, T, Lopes-Cendes, I, Lowenstein, DH, Lui, CHT, Madia, F, Magnusson, S, Marson, AG, May, P, McGraw, CM, Mei, D, Mills, JL, Minardi, R, Mirza, N, Moller, RS, Molloy, AM, Montomoli, M, Mostacci, B, Muccioli, L, Muhle, H, Mueller-Schlueter, K, Najm, IM, Nasreddine, W, Neale, BM, Neubauer, B, Newton, CRJC, Noethen, MM, Nothnagel, M, Nuernberg, P, O'Brien, TJ, Okada, Y, Olafsson, E, Oliver, KL, Ozkara, C, Palotie, A, Pangilinan, F, Papacostas, SS, Parrini, E, Pato, CN, Pato, MT, Pendziwiat, M, Petrovski, S, Pickrell, WO, Pinsky, R, Pippucci, T, Poduri, A, Pondrelli, F, Powell, RHW, Privitera, M, Rademacher, A, Radtke, R, Ragona, F, Rau, S, Rees, MI, Regan, BM, Reif, PS, Rhelms, S, Riva, A, Rosenow, F, Ryvlin, P, Saarela, A, Sadleir, LG, Sander, JW, Sander, T, Scala, M, Scattergood, T, Schachter, SC, Schankin, CJ, Scheffer, IE, Schmitz, B, Schoch, S, Schubert-Bast, S, Schulze-Bonhage, A, Scudieri, P, Sham, P, Sheidley, BR, Shih, JJ, Sills, GJ, Sisodiya, SM, Smith, MC, Smith, PE, Sonsma, ACM, Speed, D, Sperling, MR, Stefansson, H, Stefansson, K, Steinhoff, BJ, Stephani, U, Stewart, WC, Stipa, C, Striano, P, Stroink, H, Strzelczyk, A, Surges, R, Suzuki, T, Tan, KM, Taneja, RS, Tanteles, GA, Tauboll, E, Thio, LL, Thomas, GN, Thomas, RH, Timonen, O, Tinuper, P, Todaro, M, Topaloglu, P, Tozzi, R, Tsai, M-H, Tumiene, B, Turkdogan, D, Unnsteinsdottir, U, Utkus, A, Vaidiswaran, P, Valton, L, van Baalen, A, Vetro, A, Vining, EPG, Visscher, F, von Brauchitsch, S, von Wrede, R, Wagner, RG, Weber, YG, Weckhuysen, S, Weisenberg, J, Weller, M, Widdess-Walsh, P, Wolff, M, Wolking, S, Wu, D, Yamakawa, K, Yang, W, Yapici, Z, Yucesan, E, Zagaglia, S, Zahnert, F, Zara, F, Zhou, W, Zimprich, F, Zsurka, G, and Ali, QZ
Abstract: Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.
Published: 2023

11. Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.

Author: Happ, HC, Sadleir, LG, Zemel, M, de Valles-Ibáñez, G, Hildebrand, MS, McConkie-Rosell, A, McDonald, M, May, H, Sands, T, Aggarwal, V, Elder, C, Feyma, T, Bayat, A, Møller, RS, Fenger, CD, Klint Nielsen, JE, Datta, AN, Gorman, KM, King, MD, Linhares, ND, Burton, BK, Paras, A, Ellard, S, Rankin, J, Shukla, A, Majethia, P, Olson, RJ, Muthusamy, K, Schimmenti, LA, Starnes, K, Sedláčková, L, Štěrbová, K, Vlčková, M, Laššuthová, P, Jahodová, A, Porter, BE, Couque, N, Colin, E, Prouteau, C, Collet, C, Smol, T, Caumes, R, Vansenne, F, Bisulli, F, Licchetta, L, Person, R, Torti, E, McWalter, K, Webster, R, Gerard, EE, Lesca, G, Szepetowski, P, Scheffer, IE, Mefford, HC, Carvill, GL, Happ, HC, Sadleir, LG, Zemel, M, de Valles-Ibáñez, G, Hildebrand, MS, McConkie-Rosell, A, McDonald, M, May, H, Sands, T, Aggarwal, V, Elder, C, Feyma, T, Bayat, A, Møller, RS, Fenger, CD, Klint Nielsen, JE, Datta, AN, Gorman, KM, King, MD, Linhares, ND, Burton, BK, Paras, A, Ellard, S, Rankin, J, Shukla, A, Majethia, P, Olson, RJ, Muthusamy, K, Schimmenti, LA, Starnes, K, Sedláčková, L, Štěrbová, K, Vlčková, M, Laššuthová, P, Jahodová, A, Porter, BE, Couque, N, Colin, E, Prouteau, C, Collet, C, Smol, T, Caumes, R, Vansenne, F, Bisulli, F, Licchetta, L, Person, R, Torti, E, McWalter, K, Webster, R, Gerard, EE, Lesca, G, Szepetowski, P, Scheffer, IE, Mefford, HC, and Carvill, GL
Abstract: BACKGROUND AND OBJECTIVES: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. METHODS: We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details. RESULTS: We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death. DISCUSSION: We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenot
Published: 2023

12. A novel mutation of CLN3 associated with delayed-classic juvenile ceroid lipofuscinois and autophagic vacuolar myopathy

Author: Licchetta, L., Bisulli, F., Fietz, M., Valentino, M.L., Morbin, M., Mostacci, B., Oliver, K.L., Berkovic, S.F., and Tinuper, P.
Published: 2015
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13. Sleep disorders in adults with tuberous sclerosis complex: a questionnaire-based study

Author: Moavero, R., primary, Voci, A., additional, Romigi, A., additional, Bisulli, F., additional, Luisi, C., additional, Vigevano, F., additional, Mazzone, L., additional, Valeriani, M., additional, Curatolo, P., additional, and Bruni, O., additional
Published: 2022
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14. Paroxysmal arousals in Sleep-related Hypermotor Epilepsy (SHE) and Simple arousal movements in Disorders of Arousal (DoA): semiological and clinical features make a difference

Author: Loddo, G., primary, Baldassarri, L., additional, Zenesini, C., additional, Licchetta, L., additional, Bisulli, F., additional, Cirignotta, F., additional, Mondini, S., additional, Tinuper, P., additional, and Provini, F., additional
Published: 2022
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15. The Arousal Disorders Questionnaire: a new and effective screening tool

Author: Loddo, G., primary, La Fauci, G., additional, Vignatelli, L., additional, Zenesini, C., additional, Cilea, R., additional, Mignani, F., additional, Cecere, A., additional, Mondini, S., additional, Baldelli, L., additional, Bisulli, F., additional, Licchetta, L., additional, Mostacci, B., additional, Guaraldi, P., additional, Giannini, G., additional, Tinuper, P., additional, and Provini, F., additional
Published: 2022
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16. Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy

Author: Baldin, Elisa, Testoni, Stefania, de Pasqua, Silvia, Ferro, Salvatore, Albani, Fiorenzo, Baruzzi, Agostino, D’Alessandro, Roberto, Baruzzi, A., Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Cavallo, M., Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, E., Biasini, C., Cavanna, L., Guidetti, D., Marcello, N., Pisanello, A., Cremonini, A. M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Faedi, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Fallica, E., Granieri, E., Latini, F., Lelli, G., Monetti, C., Saletti, A., Schivalocchi, R., Seraceni, S., Tola, M. R., Urbini, B., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., and On behalf of PERNO study group
Published: 2017
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17. Cannabidiol in Pharmacoresistant Epilepsy: Clinical Pharmacokinetic Data From an Expanded Access Program

Author: Contin M., Mohamed S., Santucci M., Lodi M. A. M., Russo E., Mecarelli O., Bisulli F., Boni A., Cantalupo G., Cesaroni E., Coppola A., Di Bonaventura C., Fetta A., La Neve A., Matricardi S., Michelucci R., Papa A., Pilolli N., Pulitano P., Ragona F., Russo P., Striano P., Volpi L., Zucca C., Contin, M., Mohamed, S., Santucci, M., Lodi, M. A. M., Russo, E., Mecarelli, O., Bisulli, F., Boni, A., Cantalupo, G., Cesaroni, E., Coppola, A., Di Bonaventura, C., Fetta, A., La Neve, A., Matricardi, S., Michelucci, R., Papa, A., Pilolli, N., Pulitano, P., Ragona, F., Russo, P., Striano, P., Volpi, L., and Zucca, C.
Subjects: 0301 basic medicine, medicine.medical_specialty, Evening, Gastroenterology, 03 medical and health sciences, cannabidiol, 0302 clinical medicine, Dravet syndrome, Pharmacokinetics, Internal medicine, medicine, Pharmacology (medical), antiseizure medication, Pharmacology, business.industry, epilepsy, Lennox–Gastaut syndrome, pharmacokinetics, lcsh:RM1-950, Venous blood, Brief Research Report, medicine.disease, digestive system diseases, 030104 developmental biology, lcsh:Therapeutics. Pharmacology, Concomitant, Expanded access, business, Cannabidiol, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background and Aim: Data on the clinical pharmacokinetics of cannabidiol (CBD) are scanty. We explored the effect of demographic and clinical variables on plasma concentrations of purified CBD in patients with Dravet (DS) and Lennox–Gastaut syndrome (LGS).Methods: The study design was an open, prospective, multicenter expanded access program (EAP). Venous blood samples were drawn from patients between 8 and 9 am, before the CBD morning dose, 12 h apart from the last evening dose, and then 2.5 h after their usual morning dose.Results: We collected 127 plasma samples (67-morning pre-dosing and 60 post-dosing) from 43 patients (24 females, 19 males), 27 with LGS and 16 with DS. Mean ± standard deviation age was 26 ± 15 years. Duration of CBD treatment averaged 4.2 ± 2.9 months at 13.2 ± 4.6 mg/kg/day. CBD median trough plasma concentration was 91 ng/ml; it doubled to 190 ng/ml 2.5 h post-dosing (p < 0.001). Cannabidiol trough plasma concentrations were linearly related to daily doses (r = 0.564, p < 0.001). Median trough CBD plasma concentration-to-weight-adjusted dose ratio (C/D) was 32% higher (p < 0.02) in plasma samples from subjects aged 18 and over than in those under 18. Sex and concomitant antiseizure medications (ASMs) were not associated with significant variations in CBD C/D, but caution is required due to the potential influence of confounders.Conclusion: These are the first data on CBD pharmacokinetics in children and adults with LGS or DS in a real-world setting. The most relevant finding was the higher CBD C/D in adults. In practice, reduced weight-normalized doses might be required with aging to achieve the same CBD plasma levels.
Published: 2021

18. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author: Florian R. T., Kraft F., Leitao E., Kaya S., Klebe S., Magnin E., van Rootselaar A. -F., Buratti J., Kuhnel T., Schroder C., Giesselmann S., Tschernoster N., Altmueller J., Lamiral A., Keren B., Nava C., Bouteiller D., Forlani S., Jornea L., Kubica R., Ye T., Plassard D., Jost B., Meyer V., Deleuze J. -F., Delpu Y., Avarello M. D. M., Vijfhuizen L. S., Rudolf G., Hirsch E., Kroes T., Reif P. S., Rosenow F., Ganos C., Vidailhet M., Thivard L., Mathieu A., Bourgeron T., Kurth I., Rafehi H., Steenpass L., Horsthemke B., Berkovic S. F., Bisulli F., Brancati F., Canafoglia L., Casari G., Guerrini R., Ishiura H., Licchetta L., Mei D., Pippucci T., Sadleir L., Scheffer I. E., Striano P., Tinuper P., Tsuji S., Zara F., LeGuern E., Klein K. M., Labauge P., Bennett M. F., Bahlo M., Gecz J., Corbett M. A., Tijssen M. A. J., van den Maagdenberg A. M. J. M., Depienne C., Florian, R. T., Kraft, F., Leitao, E., Kaya, S., Klebe, S., Magnin, E., van Rootselaar, A. -F., Buratti, J., Kuhnel, T., Schroder, C., Giesselmann, S., Tschernoster, N., Altmueller, J., Lamiral, A., Keren, B., Nava, C., Bouteiller, D., Forlani, S., Jornea, L., Kubica, R., Ye, T., Plassard, D., Jost, B., Meyer, V., Deleuze, J. -F., Delpu, Y., Avarello, M. D. M., Vijfhuizen, L. S., Rudolf, G., Hirsch, E., Kroes, T., Reif, P. S., Rosenow, F., Ganos, C., Vidailhet, M., Thivard, L., Mathieu, A., Bourgeron, T., Kurth, I., Rafehi, H., Steenpass, L., Horsthemke, B., Berkovic, S. F., Bisulli, F., Brancati, F., Canafoglia, L., Casari, G., Guerrini, R., Ishiura, H., Licchetta, L., Mei, D., Pippucci, T., Sadleir, L., Scheffer, I. E., Striano, P., Tinuper, P., Tsuji, S., Zara, F., Leguern, E., Klein, K. M., Labauge, P., Bennett, M. F., Bahlo, M., Gecz, J., Corbett, M. A., Tijssen, M. A. J., van den Maagdenberg, A. M. J. M., Depienne, C., Institute of Human Genetics - Institut für Humangenetik [Essen], Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen)-Universitat Duisberg-Essen, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre for Molecular Medicine Cologne [Cologne] (CMMC), University Hospital of Cologne [Cologne], Cologne Center for Genomics [Cologne] (CCG), University of Cologne, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), genomic vision, Leiden University Medical Center (LUMC), Universiteit Leiden, Centre de référence des épilepsies rares [CHRU Strasbourg] (CRéER), Centre Hospitalier Régional Universitaire de Strasbourg (CHRU de Strasbourg), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, School of Biological Sciences [Adelaïde], University of Adelaide, Goethe-University Frankfurt am Main, Philipps Universität Marburg = Philipps University of Marburg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Epilepsy Research Centre, University of Calgary, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), University Medical Center Groningen [Groningen] (UMCG), This study has been financially supported by three different grants from the Fondation Maladies rares to C.D. (2009, 2010, 2016), Assistance Publique des Hôpitaux de Paris (APHP), INSERM, the 'Investissements d’Avenir' programme ANR-10-IAIHU-06 (IHU-A-ICM), University Duisburg-Essen and University Hospital Essen. M.B. was supported by an Australian National Health and Medical Research Council (NHMRC) Program Grant (GNT1054618) and an NHMRC Senior Research Fellowship (GNT1102971). This work was also supported by the Victorian Government’s Operational Infrastructure Support Program and the NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS). Laura Canafoglia: Member of the European Reference Network on Rare and Complex epilepsies, ERN EpiCARE., We thank the families for their participation in this study, Agnès Rastetter (ICM, Paris, France) for RNA extraction, and Emmanuelle Apartis (Hôpital Saint-Antoine, Paris, France) for electrophysiological assessment of Family 1. DNA extraction and cell culture of lymphoblasts have been performed at the DNA and cell bank of ICM (Paris, France). RNA-seq has been performed on the GenomEast platform of IGBMC, Illkirch, France. WGS has been performed by the Centre National de Recherche en Génomique Humaine (CNRGH) Institut de Biologie François Jacob, Evry, France. We thank Jean-Louis Mandel and Nicolas Charlet-Berguerand (IGBMC, Strasbourg, France), Cécile Cazeneuve (Hôpital Pitié-Salpêtrière, Paris, France), Charles Marcaillou (Integragen, Evry, France) and Isabel Silveira (Porto, Portugal) for valuable discussions., FAME consortium : Berkovic SF, Bisulli F, Brancati F, Canafoglia L, Casari G, Guerrini R, Ishiura H, Licchetta L, Mei D, Pippucci T, Sadleir L, Scheffer IE, Striano P, Tinuper P, Tsuji S, Zara F., Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Recherche en Génomique Humaine (CNRGH), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), RWTH Aachen University, Universität Duisburg-Essen [Essen], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Philipps University of Marburg, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Rahel T. Florian, Florian Kraft, Elsa Leitão, Sabine Kaya, Stephan Klebe, Eloi Magnin, Anne-Fleur van Rootselaar, Julien Buratti, Theresa Kühnel, Christopher Schröder, Sebastian Giesselmann, Nikolai Tschernoster, Janine Altmueller, Anaide Lamiral, Boris Keren, Caroline Nava, Delphine Bouteiller, Sylvie Forlani, Ludmila Jornea, Regina Kubica, Tao Ye, Damien Plassard, Bernard Jost, Vincent Meyer, Jean-François Deleuze, Yannick Delpu, Mario D.M. Avarello, Lisanne S. Vijfhuizen, Gabrielle Rudolf, Edouard Hirsch, Thessa Kroes, Philipp S. Reif, Felix Rosenow, Christos Ganos, Marie Vidailhet, Lionel Thivard, Alexandre Mathieu, Thomas Bourgeron, Ingo Kurth, Haloom Rafehi, Laura Steenpass, Bernhard Horsthemke, FAME consortium, Eric LeGuern, Karl Martin Klein, Pierre Labauge, Mark F. Bennett, Melanie Bahlo, Jozef Gecz, Mark A. Corbett, Marina A.J. Tijssen, Arn M.J.M. van den Maagdenberg, Christel Depienne, Francesca Bisulli, Laura Licchetta, Paolo Tinuper, MATHIEU, Alexandre, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Male, MESH: Introns, [SDV]Life Sciences [q-bio], Medizin, MESH: DNA Repeat Expansion, Epilepsies, Myoclonic, [SDV.GEN] Life Sciences [q-bio]/Genetics, MARCH6, expansion, MESH: Ubiquitin-Protein Ligases/genetics, MESH: Aged, MESH: Middle Aged, DNA Repeat Expansion, Neurodegenerative diseases, MESH: Epilepsies, Myoclonic, Chromosome Mapping, Middle Aged, MESH: Epilepsies, Myoclonic/genetics, Pedigree, MESH: Young Adult, Female, ddc:500, MESH: Membrane Proteins, Technology Platforms, Genomic instability, Adult, Adolescent, MESH: Pedigree, Ubiquitin-Protein Ligases, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Familial Adult Myoclonic Epilepsy type 3, Article, Young Adult, Humans, Aged, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Epilepsy, Membrane Proteins, MESH: Adult, MESH: Membrane Proteins/genetics, MESH: Ubiquitin-Protein Ligases, MESH: Male, Introns, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Chromosome Mapping, MESH: Female, Neurological disorders
Abstract: Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements., Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.
Published: 2019

19. Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study

Author: Franceschi, Enrico, Depenni, Roberta, Paccapelo, Alexandro, Ermani, Mario, Faedi, Marina, Sturiale, Carmelo, Michiara, Maria, Servadei, Franco, Pavesi, Giacomo, Urbini, Benedetta, Pisanello, Anna, Crisi, Girolamo, Cavallo, Michele A., Dazzi, Claudio, Biasini, Claudia, Bertolini, Federica, Mucciarini, Claudia, Pasini, Giuseppe, Baruzzi, Agostino, Brandes, Alba A., Baruzzi, A., Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Cavallo, M., Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, E., Biasini, C., Cavanna, L., Guidetti, D., Marcello, N., Pisanello, A., Cremonini, A. M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., PastoreTrossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Faedi, M., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, M., Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M. R., Urbini, B., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., and The PERNO Study Group
Published: 2017
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20. Epilepsy with auditory features: Contribution of known genes in 112 patients

Author: Bisulli, F., Rinaldi, C., Pippucci, T., Minardi, R., Baldassari, S., Zenesini, C., Mostacci, B., Fanella, M., Avoni, P., Menghi, V., Caporali, L., Muccioli, L., Tinuper, P., and Licchetta, L.
Published: 2021
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21. Postictal Psychosis in Epilepsy: A Clinicogenetic Study

Author: Braatz, V, Custodio, HM, Leu, C, Agro, L, Wang, B, Calafato, S, Rayner, G, Doyle, MG, Hengsbach, C, Bisulli, F, Weber, YG, Gambardella, A, Delanty, N, Cavalleri, G, Foong, J, Scheffer, IE, Berkovic, SF, Bramon, E, Balestrini, S, Sisodiya, SM, Braatz, V, Custodio, HM, Leu, C, Agro, L, Wang, B, Calafato, S, Rayner, G, Doyle, MG, Hengsbach, C, Bisulli, F, Weber, YG, Gambardella, A, Delanty, N, Cavalleri, G, Foong, J, Scheffer, IE, Berkovic, SF, Bramon, E, Balestrini, S, and Sisodiya, SM
Abstract: OBJECTIVE: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy-related psychoses, and has unknown causation. METHODS: We conducted a case-control cohort study including patients diagnosed with postictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile, and outcomes. After screening 3,288 epilepsy patients, we identified 83 with psychosis; 49 had postictal psychosis. Controls were 98 adults, matched by age and epilepsy type, with no history of psychosis. Logistic regression was used to investigate clinical factors associated with postictal psychosis; univariate associations with a p value < 0.20 were used to build a multivariate model. Polygenic risk scores for schizophrenia were calculated. RESULTS: Cases were more likely to have seizure clustering (odds ratio [OR] = 7.59, p < 0.001), seizures with a recollected aura (OR = 2.49, p = 0.013), and a family history of psychiatric disease (OR = 5.17, p = 0.022). Cases showed predominance of right temporal epileptiform discharges (OR = 4.87, p = 0.007). There was no difference in epilepsy duration, neuroimaging findings, or antiseizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of postictal psychosis cases (n = 58) were significantly higher than in 1,366 epilepsy controls (R2 = 3%, p = 6 × 10-3 ), but not significantly different from 945 independent patients with schizophrenia (R2 = 0.1%, p = 0.775). INTERPRETATION: Postictal psychosis occurs under particular circumstances in people with epilepsy with a heightened genetic predisposition to schizophrenia, illustrating how disease biology (seizures) and trait susceptibility (schizophrenia) may interact to produce particular outcomes (postictal psychosis) in a common disease. ANN NEUROL 2021;90:464-476.
Published: 2021

22. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

Author: Motelow, JE, Povysil, G, Dhindsa, RS, Stanley, KE, Allen, AS, Feng, Y-CA, Howrigan, DP, Abbott, LE, Tashman, K, Cerrato, F, Cusick, C, Singh, T, Heyne, H, Byrnes, AE, Churchhouse, C, Watts, N, Solomonson, M, Lal, D, Gupta, N, Neale, BM, Cavalleri, GL, Cossette, P, Cotsapas, C, De Jonghe, P, Dixon-Salazar, T, Guerrini, R, Hakonarson, H, Heinzen, EL, Helbig, I, Kwan, P, Marson, AG, Petrovski, S, Kamalakaran, S, Sisodiya, SM, Stewart, R, Weckhuysen, S, Depondt, C, Dlugos, DJ, Scheffer, IE, Striano, P, Freyer, C, Krause, R, May, P, McKenna, K, Regan, BM, Bennett, CA, Leu, C, Leech, SL, O'Brien, TJ, Todaro, M, Stamberger, H, Andrade, DM, Ali, QZ, Sadoway, TR, Krestel, H, Schaller, A, Papacostas, SS, Kousiappa, I, Tanteles, GA, Christou, Y, Sterbova, K, Vlckova, M, Sedlackova, L, Lassuthova, P, Klein, KM, Rosenow, F, Reif, PS, Knake, S, Neubauer, BA, Zimprich, F, Feucht, M, Reinthaler, EM, Kunz, WS, Zsurka, G, Surges, R, Baumgartner, T, von Wrede, R, Pendziwiat, M, Muhle, H, Rademacher, A, van Baalen, A, von Spiczak, S, Stephani, U, Afawi, Z, Korczyn, AD, Kanaan, M, Canavati, C, Kurlemann, G, Muller-Schluter, K, Kluger, G, Haeusler, M, Blatt, I, Lemke, JR, Krey, I, Weber, YG, Wolking, S, Becker, F, Lauxmann, S, Bosselmann, C, Kegele, J, Hengsbach, C, Rau, S, Steinhoff, BJ, Schulze-Bonhage, A, Borggraefe, I, Schankin, CJ, Schubert-Bast, S, Schreiber, H, Mayer, T, Korinthenberg, R, Brockmann, K, Wolff, M, Dennig, D, Madeleyn, R, Kalviainen, R, Saarela, A, Timonen, O, Linnankivi, T, Lehesjoki, A-E, Rheims, S, Lesca, G, Ryvlin, P, Maillard, L, Valton, L, Derambure, P, Bartolomei, F, Hirsch, E, Michel, V, Chassoux, F, Rees, M, Chung, S-K, Pickrell, WO, Powell, R, Baker, MD, Fonferko-Shadrach, B, Lawthom, C, Anderson, J, Schneider, N, Balestrini, S, Zagaglia, S, Braatz, V, Johnson, MR, Auce, P, Sills, GJ, Baum, LW, Sham, PC, Cherny, SS, Lui, CHT, Delanty, N, Doherty, CP, Shukralla, A, El-Naggar, H, Widdess-Walsh, P, Barisi, N, Canafoglia, L, Franceschetti, S, Castellotti, B, Granata, T, Ragona, F, Zara, F, Iacomino, M, Riva, A, Madia, F, Vari, MS, Salpietro, V, Scala, M, Mancardi, MM, Nobili, L, Amadori, E, Giacomini, T, Bisulli, F, Pippucci, T, Licchetta, L, Minardi, R, Tinuper, P, Muccioli, L, Mostacci, B, Gambardella, A, Labate, A, Annesi, G, Manna, L, Gagliardi, M, Parrini, E, Mei, D, Vetro, A, Bianchini, C, Montomoli, M, Doccini, V, Barba, C, Hirose, S, Ishii, A, Suzuki, T, Inoue, Y, Yamakawa, K, Beydoun, A, Nasreddine, W, Zgheib, NK, Tumiene, B, Utkus, A, Sadleir, LG, King, C, Caglayan, SH, Arslan, M, Yapici, Z, Topaloglu, P, Kara, B, Yis, U, Turkdogan, D, Gundogdu-Eken, A, Bebek, N, Tsai, M-H, Ho, C-J, Lin, C-H, Lin, K-L, Chou, I-J, Poduri, A, Shiedley, BR, Shain, C, Noebels, JL, Goldman, A, Busch, RM, Jehi, L, Najm, IM, Ferguson, L, Khoury, J, Glauser, TA, Clark, PO, Buono, RJ, Ferraro, TN, Sperling, MR, Lo, W, Privitera, M, French, JA, Schachter, S, Kuzniecky, R, Devinsky, O, Hegde, M, Greenberg, DA, Ellis, CA, Goldberg, E, Helbig, KL, Cosico, M, Vaidiswaran, P, Fitch, E, Berkovic, SF, Lerche, H, Lowenstein, DH, Goldstein, DB, Motelow, JE, Povysil, G, Dhindsa, RS, Stanley, KE, Allen, AS, Feng, Y-CA, Howrigan, DP, Abbott, LE, Tashman, K, Cerrato, F, Cusick, C, Singh, T, Heyne, H, Byrnes, AE, Churchhouse, C, Watts, N, Solomonson, M, Lal, D, Gupta, N, Neale, BM, Cavalleri, GL, Cossette, P, Cotsapas, C, De Jonghe, P, Dixon-Salazar, T, Guerrini, R, Hakonarson, H, Heinzen, EL, Helbig, I, Kwan, P, Marson, AG, Petrovski, S, Kamalakaran, S, Sisodiya, SM, Stewart, R, Weckhuysen, S, Depondt, C, Dlugos, DJ, Scheffer, IE, Striano, P, Freyer, C, Krause, R, May, P, McKenna, K, Regan, BM, Bennett, CA, Leu, C, Leech, SL, O'Brien, TJ, Todaro, M, Stamberger, H, Andrade, DM, Ali, QZ, Sadoway, TR, Krestel, H, Schaller, A, Papacostas, SS, Kousiappa, I, Tanteles, GA, Christou, Y, Sterbova, K, Vlckova, M, Sedlackova, L, Lassuthova, P, Klein, KM, Rosenow, F, Reif, PS, Knake, S, Neubauer, BA, Zimprich, F, Feucht, M, Reinthaler, EM, Kunz, WS, Zsurka, G, Surges, R, Baumgartner, T, von Wrede, R, Pendziwiat, M, Muhle, H, Rademacher, A, van Baalen, A, von Spiczak, S, Stephani, U, Afawi, Z, Korczyn, AD, Kanaan, M, Canavati, C, Kurlemann, G, Muller-Schluter, K, Kluger, G, Haeusler, M, Blatt, I, Lemke, JR, Krey, I, Weber, YG, Wolking, S, Becker, F, Lauxmann, S, Bosselmann, C, Kegele, J, Hengsbach, C, Rau, S, Steinhoff, BJ, Schulze-Bonhage, A, Borggraefe, I, Schankin, CJ, Schubert-Bast, S, Schreiber, H, Mayer, T, Korinthenberg, R, Brockmann, K, Wolff, M, Dennig, D, Madeleyn, R, Kalviainen, R, Saarela, A, Timonen, O, Linnankivi, T, Lehesjoki, A-E, Rheims, S, Lesca, G, Ryvlin, P, Maillard, L, Valton, L, Derambure, P, Bartolomei, F, Hirsch, E, Michel, V, Chassoux, F, Rees, M, Chung, S-K, Pickrell, WO, Powell, R, Baker, MD, Fonferko-Shadrach, B, Lawthom, C, Anderson, J, Schneider, N, Balestrini, S, Zagaglia, S, Braatz, V, Johnson, MR, Auce, P, Sills, GJ, Baum, LW, Sham, PC, Cherny, SS, Lui, CHT, Delanty, N, Doherty, CP, Shukralla, A, El-Naggar, H, Widdess-Walsh, P, Barisi, N, Canafoglia, L, Franceschetti, S, Castellotti, B, Granata, T, Ragona, F, Zara, F, Iacomino, M, Riva, A, Madia, F, Vari, MS, Salpietro, V, Scala, M, Mancardi, MM, Nobili, L, Amadori, E, Giacomini, T, Bisulli, F, Pippucci, T, Licchetta, L, Minardi, R, Tinuper, P, Muccioli, L, Mostacci, B, Gambardella, A, Labate, A, Annesi, G, Manna, L, Gagliardi, M, Parrini, E, Mei, D, Vetro, A, Bianchini, C, Montomoli, M, Doccini, V, Barba, C, Hirose, S, Ishii, A, Suzuki, T, Inoue, Y, Yamakawa, K, Beydoun, A, Nasreddine, W, Zgheib, NK, Tumiene, B, Utkus, A, Sadleir, LG, King, C, Caglayan, SH, Arslan, M, Yapici, Z, Topaloglu, P, Kara, B, Yis, U, Turkdogan, D, Gundogdu-Eken, A, Bebek, N, Tsai, M-H, Ho, C-J, Lin, C-H, Lin, K-L, Chou, I-J, Poduri, A, Shiedley, BR, Shain, C, Noebels, JL, Goldman, A, Busch, RM, Jehi, L, Najm, IM, Ferguson, L, Khoury, J, Glauser, TA, Clark, PO, Buono, RJ, Ferraro, TN, Sperling, MR, Lo, W, Privitera, M, French, JA, Schachter, S, Kuzniecky, R, Devinsky, O, Hegde, M, Greenberg, DA, Ellis, CA, Goldberg, E, Helbig, KL, Cosico, M, Vaidiswaran, P, Fitch, E, Berkovic, SF, Lerche, H, Lowenstein, DH, and Goldstein, DB
Abstract: Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy.
Published: 2021

23. Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox–Gastaut Syndrome

Author: Iannone, L. F., Arena, G., Battaglia, Domenica Immacolata, Bisulli, F., Bonanni, P., Boni, A., Canevini, M. P., Cantalupo, G., Cesaroni, E., Contin, M., Coppola, A., Cordelli, D. M., Cricchiuti, G., De Giorgis, V., De Leva, M. F., De Rinaldis, M., D'Orsi, Giovanni Maria, Elia, M., Galimberti, C. A., Morano, A., Granata, T., Guerrini, R., Lodi, M. A. M., La Neve, A., Marchese, F., Masnada, S., Michelucci, R., Nosadini, M., Pilolli, N., Pruna, D., Ragona, F., Rosati, A., Santucci, M., Spalice, A., Pietrafusa, N., Striano, P., Tartara, E., Tassi, L., Papa, A., Zucca, C., Russo, Elisa, Mecarelli, O., Battaglia D. (ORCID:0000-0003-0491-4021), d'Orsi G., Russo E., Iannone, L. F., Arena, G., Battaglia, Domenica Immacolata, Bisulli, F., Bonanni, P., Boni, A., Canevini, M. P., Cantalupo, G., Cesaroni, E., Contin, M., Coppola, A., Cordelli, D. M., Cricchiuti, G., De Giorgis, V., De Leva, M. F., De Rinaldis, M., D'Orsi, Giovanni Maria, Elia, M., Galimberti, C. A., Morano, A., Granata, T., Guerrini, R., Lodi, M. A. M., La Neve, A., Marchese, F., Masnada, S., Michelucci, R., Nosadini, M., Pilolli, N., Pruna, D., Ragona, F., Rosati, A., Santucci, M., Spalice, A., Pietrafusa, N., Striano, P., Tartara, E., Tassi, L., Papa, A., Zucca, C., Russo, Elisa, Mecarelli, O., Battaglia D. (ORCID:0000-0003-0491-4021), d'Orsi G., and Russo E.
Abstract: Background: Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox–Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period. Material and Methods: Thirty centers were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg per day. Adverse effects and liver function tests were assessed after 2 weeks; 1, 3, and 6 months of treatment; and periodically thereafter. Seizure endpoints were the percentage of patients with ≥50 and 100% reduction in seizures compared to baseline. Results: A total of 93 patients were enrolled and included in the safety analysis. Eighty-two patients [27 (32.9%) DS, 55 (67.1%) LGS] with at least 3 months of treatment have been included in the effectiveness analysis; median previously failed antiseizure medications was eight. Pediatric and adult patients were uniformly represented in the cohort. At 3-month follow-up, compared to the 28-day baseline period, the percentage of patients with at least a 50% reduction in seizure frequency was 40.2% (plus 1.2% seizure-free). Retention rate was similar according to diagnosis, while we found an increased number of patients remaining under treatment in the adult group. CBD was mostly coadministered with valproic acid (62.2%) and clobazam (41.5%). In the safety dataset, 29 (31.2%) dropped out: reasons were lack of efficacy [16 (17.2%)] and adverse events (AEs) [12 (12.9%)], and one met withdrawal criteria (1.1%). Most reported AEs were somnolence (22.6%) and diarrhea (11.9%), followed by transaminase elevation and loss of appetite. Conclusions: CBD is associated with improved seizure control also in a considerable proportion of highly refractory patients with DS and LGS independently from clobazam use. Overall, CBD safety and effectiveness are not dose-related in this cohort.
Published: 2021

24. Declining malformation rates with changed antiepileptic drug prescribing: An observational study

Author: Tomson T., Battino D., Bonizzoni E., Craig J., Lindhout D., Perucca E., Sabers A., Thomas S. V., Vajda F., Bisulli F., Tinuper P., for the EURAP Study Group, Tomson T., Battino D., Bonizzoni E., Craig J., Lindhout D., Perucca E., Sabers A., Thomas S.V., Vajda F., Bisulli F., Tinuper P., and for the EURAP Study Group
Subjects: Pediatrics, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Medicina Clínica, EURAP, Lamotrigine, Epilepsia, 03 medical and health sciences, Epilepsy, Neurologia, 0302 clinical medicine, AED, purl.org/becyt/ford/3.2 [https], medicine, 030212 general & internal medicine, Medical prescription, Prospective cohort study, Valproic Acid, Pregnancy, business.industry, Neurología Clínica, Carbamazepine, medicine.disease, epilepsy, purl.org/becyt/ford/3 [https], sense organs, pregnancy, Neurology (clinical), Levetiracetam, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Objective Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP). Methods EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000–2005 (n = 4,760), 2006–2009 (n = 3,599), and 2010–2013 (n = 2,949). Results There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000–2005 to 4.4% in 2010–2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy. Conclusions There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events. Fil: Tomson, Torbjörn. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Battino, Dina. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Thomas, Sanjeev V.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Vajda, Frank. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Kochen, Sara Silvia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Craig, John. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Binozzoni, Erminio. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Lindhout, Dick. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Perucca, Emilio. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Sabers, Anne. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Published: 2019

25. Polygenic burden in focal and generalized epilepsies

Author: Leu C., Stevelink R., Smith A. W., Goleva S. B., Kanai M., Ferguson L., Campbell C., Kamatani Y., Okada Y., Sisodiya S. M., Cavalleri G. L., Koeleman B. P. C., Lerche H., Jehi L., Davis L. K., Najm I. M., Palotie A., Daly M. J., Busch R. M., Lal D., Feng Y. -C. A., Howrigan D. P., Abbott L. E., Tashman K., Cerrato F., Churchhouse C., Gupta N., Neale B. M., Berkovic S. F., Goldstein D. B., Lowenstein D. H., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Hakonarson H., Heinzen E. L., Helbig I., Kwan P., Marson A. G., Petrovski S., Kamalakaran S., Stewart R., Weckhuysen S., Depondt C., Dlugos D. J., Scheffer I. E., Striano P., Freyer C., Krause R., May P., McKenna K., Regan B. M., Bellows S. T., Bennett C. A., Johns E. M. C., Macdonald A., Shilling H., Burgess R., Weckhuysen D., Bahlo M., O'Brien T. J., Todaro M., Stamberger H., Andrade D. M., Sadoway T. R., Mo K., Krestel H., Gallati S., Papacostas S. S., Kousiappa I., Tanteles G. A., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K. M., Rosenow F., Reif P. S., Knake S., Kunz W. S., Zsurka G., Elger C. E., Bauer J., Rademacher M., Pendziwiat M., Muhle H., Rademacher A., Van Baalen A., Von Spiczak S., Stephani U., Afawi Z., Korczyn A. D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J. R., Krey I., Weber Y. G., Wolking S., Becker F., Hengsbach C., Rau S., Maisch A. F., Steinhoff B. J., Schulze-Bonhage A., Schubert-Bast S., Schreiber H., Borggrafe I., Schankin C. J., Mayer T., Korinthenberg R., Brockmann K., Dennig D., Madeleyn R., Kalviainen R., Auvinen P., Saarela A., Linnankivi T., Lehesjoki A. -E., Rees M. I., Chung S. -K., Pickrell W. O., Powell R., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M. R., Auce P., Sills G. J., Baum L. W., Sham P. C., Cherny S. S., Lui C. H. T., Barisic N., Delanty N., Doherty C. P., Shukralla A., McCormack M., El-Naggar H., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Zara F., Iacomino M., Madia F., Vari M. S., Mancardi M. M., Salpietro V., Bisulli F., Tinuper P., Licchetta L., Pippucci T., Stipa C., Muccioli L., Minardi R., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Marini C., Suzuki T., Inoue Y., Yamakawa K., Birute T., Ruta M., Algirdas U., Ruta P., Jurgita G., Ruta S., Sadleir L. G., King C., Mountier E., Caglayan S. H., Arslan M., Yapici Z., Yis U., Topaloglu P., Kara B., Turkdogan D., Gundogdu-Eken A., Bebek N., Ugur-Iseri S., Baykan B., Salman B., Haryanyan G., Yucesan E., Kesim Y., Ozkara C., Sheidley B. R., Shain C., Poduri A., Buono R. J., Ferraro T. N., Sperling M. R., Lo W., Privitera M., French J. A., Schachter S., Kuzniecky R. I., Devinsky O., Hegde M., Khankhanian P., Helbig K. L., Ellis C. A., Spalletta G., Piras F., Gili T., Ciullo V., Leu C., Stevelink R., Smith A.W., Goleva S.B., Kanai M., Ferguson L., Campbell C., Kamatani Y., Okada Y., Sisodiya S.M., Cavalleri G.L., Koeleman B.P.C., Lerche H., Jehi L., Davis L.K., Najm I.M., Palotie A., Daly M.J., Busch R.M., Lal D., Feng Y.-C.A., Howrigan D.P., Abbott L.E., Tashman K., Cerrato F., Churchhouse C., Gupta N., Neale B.M., Berkovic S.F., Goldstein D.B., Lowenstein D.H., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Hakonarson H., Heinzen E.L., Helbig I., Kwan P., Marson A.G., Petrovski S., Kamalakaran S., Stewart R., Weckhuysen S., Depondt C., Dlugos D.J., Scheffer I.E., Striano P., Freyer C., Krause R., May P., McKenna K., Regan B.M., Bellows S.T., Bennett C.A., Johns E.M.C., Macdonald A., Shilling H., Burgess R., Weckhuysen D., Bahlo M., O'Brien T.J., Todaro M., Stamberger H., Andrade D.M., Sadoway T.R., Mo K., Krestel H., Gallati S., Papacostas S.S., Kousiappa I., Tanteles G.A., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K.M., Rosenow F., Reif P.S., Knake S., Kunz W.S., Zsurka G., Elger C.E., Bauer J., Rademacher M., Pendziwiat M., Muhle H., Rademacher A., Van Baalen A., Von Spiczak S., Stephani U., Afawi Z., Korczyn A.D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J.R., Krey I., Weber Y.G., Wolking S., Becker F., Hengsbach C., Rau S., Maisch A.F., Steinhoff B.J., Schulze-Bonhage A., Schubert-Bast S., Schreiber H., Borggrafe I., Schankin C.J., Mayer T., Korinthenberg R., Brockmann K., Dennig D., Madeleyn R., Kalviainen R., Auvinen P., Saarela A., Linnankivi T., Lehesjoki A.-E., Rees M.I., Chung S.-K., Pickrell W.O., Powell R., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M.R., Auce P., Sills G.J., Baum L.W., Sham P.C., Cherny S.S., Lui C.H.T., Barisic N., Delanty N., Doherty C.P., Shukralla A., McCormack M., El-Naggar H., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Zara F., Iacomino M., Madia F., Vari M.S., Mancardi M.M., Salpietro V., Bisulli F., Tinuper P., Licchetta L., Pippucci T., Stipa C., Muccioli L., Minardi R., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Marini C., Suzuki T., Inoue Y., Yamakawa K., Birute T., Ruta M., Algirdas U., Ruta P., Jurgita G., Ruta S., Sadleir L.G., King C., Mountier E., Caglayan S.H., Arslan M., Yapici Z., Yis U., Topaloglu P., Kara B., Turkdogan D., Gundogdu-Eken A., Bebek N., Ugur-Iseri S., Baykan B., Salman B., Haryanyan G., Yucesan E., Kesim Y., Ozkara C., Sheidley B.R., Shain C., Poduri A., Buono R.J., Ferraro T.N., Sperling M.R., Lo W., Privitera M., French J.A., Schachter S., Kuzniecky R.I., Devinsky O., Hegde M., Khankhanian P., Helbig K.L., Ellis C.A., Spalletta G., Piras F., Gili T., Ciullo V., Commission of the European Communities, Medical Research Council (MRC), Tumienė, Birutė, Mameniškienė, Rūta, Utkus, Algirdas, Praninskienė, Rūta, Grikinienė, Jurgita, Samaitienė-Aleknienė, Rūta, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Helsinki Institute of Life Science HiLIFE, and Department of Medical and Clinical Genetics
Subjects: 0301 basic medicine, Male, Multifactorial Inheritance, Epi25 Consortium, Databases, Factual, FEATURES, Genome-wide association study, Epilepsies, 3124 Neurology and psychiatry, Cohort Studies, Epilepsy, 0302 clinical medicine, Cost of Illness, 1ST SEIZURE, HISTORY, genetics, POPULATION, 11 Medical and Health Sciences, education.field_of_study, medicine.diagnostic_test, SCORES, Single Nucleotide, Biobank, 3. Good health, 17 Psychology and Cognitive Sciences, Genetic generalized epilepsy, Epilepsy, Generalized, Female, Partial, Cohort study, Human, medicine.medical_specialty, Population, European Continental Ancestry Group, Clinical Neurology, BIOBANK, Polymorphism, Single Nucleotide, epilepsy, genetic generalized epilepsy, common variant risk, Databases, 03 medical and health sciences, Genetic, Internal medicine, medicine, Journal Article, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, Generalized epilepsy, education, SEIZURE RECURRENCE, Factual, METAANALYSIS, Genetic testing, Neurology & Neurosurgery, RISK PREDICTION, Generalized, business.industry, 3112 Neurosciences, Common variant risk, Genetic Variation, Original Articles, medicine.disease, Comorbidity, Cost of Illne, Epilepsies, Partial, Genome-Wide Association Study, 030104 developmental biology, Neurology (clinical), Cohort Studie, business, 030217 neurology & neurosurgery
Abstract: See Hansen and Møller (doi:10.1093/brain/awz318) for a scientific commentary on this article. Using polygenic risk scores from a genome-wide association study in generalized and focal epilepsy, Leu et al. reveal a significantly higher genetic burden for epilepsy in multiple cohorts of people with epilepsy compared to population controls. Quantification of common variant burden may be valuable for epilepsy prognosis and treatment., Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10−15; Cleveland: P = 2.85×10−4; Finnish-ancestry Epi25: P = 1.80×10−4) or population controls (Epi25: P = 2.35×10−70; Cleveland: P = 1.43×10−7; Finnish-ancestry Epi25: P = 3.11×10−4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10−4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10−19; Cleveland: P = 1.69×10−6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10−15; Cleveland: P = 1.39×10−2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls—in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.
Published: 2019

26. Erratum to: Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy

Author: Baldin, Elisa, Testoni, Stefania, de Pasqua, Silvia, Ferro, Salvatore, Albani, Fiorenzo, Baruzzi, Agostino, D’Alessandro, Roberto, Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Cerasoli, S., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Visani, M., Dall’Agata, M., Faedi, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Fallica, E., Granieri, E., Latini, F., Lelli, G., Monetti, C., Saletti, A., Schivalocchi, R., Seraceni, S., Tola, M. R., Urbini, B., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., and On behalf of PERNO study group
Published: 2017
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27. Hyperkinetic manifestations in nocturnal frontal lobe epilepsy. Semeiological features and physiopathological hypothesis

Author: Tinuper, P., Provini, F., Bisulli, F., and Lugaresi, E.
Published: 2005
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28. Interobserver reliability of ICSD–R minimal diagnostic criteria for the parasomnias

Author: Vignatelli, L., Bisulli, F., Zaniboni, A., Naldi, I., Fares, J. E., Provini, F., Vetrugno, R., Plazzi, G., Tinuper, P., and Montagna, P.
Published: 2005
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29. Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy

Author: Ayerdi-Izquierdo, A., Stavrides, G., Sellés-Martínez, J.J., Larrea, L., Bovo, G., Munain, A. López de, Bisulli, F., Martí-Massó, J.F., Michelucci, R., Poza, J.J., Tinuper, P., Stephani, U., Striano, P., Striano, S., Staub, E., Sarafidou, T., Hinzmann, B., Moschonas, N., Siebert, R., Deloukas, P., Nobile, C., and Pérez-Tur, J.
Published: 2006
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30. DISTRIBUTION OF PROGRESSIVE MYOCLONUS EPILEPSIES IN ITALY; POSITIVELY DIAGNOSED AND UNCLASSIFIED PATIENTS: p827

Author: Canafoglia, L., Franceschetti, S., Michelucci, R., Magaudda, A., Rubboli, G., Tinuper, P., Striano, P., Striano, S., Gambardella, A., Neve, La A., Francavilla, T., Ferlazzo, E., Italiano, D., Gobbi, G., Villani, F., Nardocci, N., Granata, T., Veggiotti, P., Pareyson, D., Coppola, G., Uziel, G., Belcastro, V., Bisulli, F., Spreafico, R., Guerrini, R., Viri, M., Zucca, C., Capovilla, G., Giovagnoli, A. R., Canevini, M. P., Binelli, S., Casazza, M., Cantisani, A. T., Filla, A., Pezzella, M., Santucci, M., Parmeggiani, A., Posar, A., De Maria, G., Marini, C., Bianchi, A., Ragona, F., Freri, E., Mariotti, C., and Costa, P.
Published: 2012

31. NOCTURNAL FRONTAL LOBE EPILEPSY AND PARASOMNIAS DIFFERENTIAL DIAGNOSIS: ACCURACY OF TWO DIFFERENT CLINICAL DIAGNOSTIC TOOLS: p798

Author: Broli, M., Bisulli, F., Di Vito, L., Leta, C., Mostacci, B., Naldi, I., Tinuper, P., and Vignatelli, L.
Published: 2012

32. CLINICAL HETEROGENEITY IN FAMILIAL PARTIAL EPILEPSY WITH AUDITORY FEATURES NEGATIVE FOR LGI1 AND WITH MATRILINEAL INHERITANCE: p793

Author: Leta, C., Bisulli, F., Pittau, F., Licchetta, L., Stipa, C., Naldi, I., Alvisi, L., and Tinuper, P.
Published: 2012

33. EFFECTS OF VAGUS NERVE STIMULATION ON SEIZURES AND CARDIOVASCULAR RESPONSES IN PATIENTS WITH DRUG-RESISTANT EPILEPSY: p541

Author: Naldi, I., Mostacci, B., Broli, M., Guaraldi, P., Alvisi, L., Barletta, G., Pittau, F., Leta, C., Bisulli, F., Cortelli, P., and Tinuper, P.
Published: 2012

34. Gaze-evoked amaurosis heralding orbital angiomyoma. Case report

Author: Salvi F., Bernardi B., Mascalchi M., Bisulli F., Zonari P., Foschini M. P., Dina R., and Tassinari C. A.
Published: 1997
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35. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author: Florian, R.T., Kraft, F., Leitao, E., Kaya, S., Klebe, S., Magnin, E., Rootselaar, A.F. van, Buratti, J., Kuhnel, T., Schroder, C., Giesselmann, S., Tschernoster, N., Altmueller, J., Lamiral, A., Keren, B., Nava, C., Bouteiller, D., Forlani, S., Jornea, L., Kubica, R., Ye, T., Plassard, D., Jost, B., Meyer, V., Deleuze, J.F., Delpu, Y., Avarello, M.D.M., Vijfhuizen, L.S., Rudolf, G., Hirsch, E., Kroes, T., Reif, P.S., Rosenow, F., Ganos, C., Vidailhet, M., Thivard, L., Mathieu, A., Bourgeron, T., Kurth, I., Rafehi, H., Steenpass, L., Horsthemke, B., Berkovic, S.F., Bisulli, F., Brancati, F., Canafoglia, L., Casari, G., Guerrini, R., Ishiura, H., Licchetta, L., Mei, D., Pippucci, T., Sadleir, L., Scheffer, I.E., Striano, P., Tinuper, P., Tsuji, S., Zara, F., LeGuern, E., Klein, K.M., Labauge, P., Bennett, M.F., Bahlo, M., Gecz, J., Corbett, M.A., Tijssen, M.A.J., Maagdenberg, A.M.J.M. van den, Depienne, C., and FAME Consortium
Abstract: Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
Published: 2019

36. The landscape of epilepsy-related GATOR1 variants (vol 21, pg 398, 2019)

Author: Baldassari, S., Picard, F., Verbeek, N.E., Kempen, M. van, Brilstra, E.H., Lesca, G., Conti, V., Guerrini, R., Bisulli, F., Licchetta, L., Pippucci, T., Tinuper, P., Hirsch, E., Saint Martin, A. de, Chelly, J., Rudolf, G., Chipaux, M., Ferrand-Sorbets, S., Dorfmuller, G., Sisodiya, S., Balestrini, S., Schoeler, N., Hernandez-Hernandez, L., Krithika, S., Oegema, R., Hagebeuk, E., Gunning, B., Deckers, C., Berghuis, B., Wegner, I., Niks, E.H., Jansen, F.E., Braun, K., Jong, D. de, Rubboli, G., Talvik, I., Sander, V., Uldall, P., Jacquemont, M.L., Nava, C., Leguern, E., Julia, S., Gambardella, A., d'Orsi, G., Crichiutti, G., Faivre, L., Darmency, V., Benova, B., Krsek, P., Biraben, A., Lebre, A.S., Jennesson, M., Sattar, S., Marchal, C., Nordli, D.R., Lindstrom, K., Striano, P., Lomax, L.B., Kiss, C., Bartolomei, F., Lepine, A.F., Schoonjans, A.S., Stouffs, K., Jansen, A., Panagiotakaki, E., Ricard-Mousnier, B., Thevenon, J., Bellescize, J. de, Catenoix, H., Dorn, T., Zenker, M., Muller-Schluter, K., Brandt, C., Krey, I., Polster, T., Wolff, M., Balci, M., Rostasy, K., Achaz, G., Zacher, P., Becher, T., Cloppenborg, T., Yuskaitis, C.J., Weckhuysen, S., Poduri, A., Lemke, J.R., Moller, R.S., and Baulac, S.
Published: 2019

37. PROGNOSTIC FACTORS IN PATIENTS WITH MESIAL TEMPORAL LOBE EPILEPSY (MTLE): A PRELIMINARY STUDY: 091

Author: Tinuper, P., Bisulli, F., Pittau, F., Naldi, I., Avoni, P., Parmeggiani, A., Licchetta, L., Mai, R., Tassi, L., Gambardella, A., Labate, A., Quattrone, A., and Baruzzi, A.
Published: 2006

38. Nocturnal frontal lobe epilepsy and arousal disorders: chance association or common mechanisms?: 48

Author: MONTAGNA, P., BISULLI, F., NALDI, I., VIGNATELLI, L., PROVINI, F., PLAZZI, G., VETRUGNO, R., and TINUPER, P.
Published: 2006

39. Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2

Author: Corbett, MA, Kroes, T, Veneziano, L, Bennett, MF, Florian, R, Schneider, AL, Coppola, A, Licchetta, L, Franceschetti, S, Suppa, A, Wenger, A, Mei, D, Pendziwiat, M, Kaya, S, Delledonne, M, Straussberg, R, Xumerle, L, Regan, B, Crompton, D, van Rootselaar, A-F, Correll, A, Catford, R, Bisulli, F, Chakraborty, S, Baldassari, S, Tinuper, P, Barton, K, Carswell, S, Smith, M, Berardelli, A, Carroll, R, Gardner, A, Friend, KL, Blatt, I, Iacomino, M, Di Bonaventura, C, Striano, S, Buratti, J, Keren, B, Nava, C, Forlani, S, Rudolf, G, Hirsch, E, Leguern, E, Labauge, P, Balestrini, S, Sander, JW, Afawi, Z, Helbig, I, Ishiura, H, Tsuji, S, Sisodiya, SM, Casari, G, Sadleir, LG, van Coller, R, Tijssen, MAJ, Klein, KM, van den Maagdenberg, AMJM, Zara, F, Guerrini, R, Berkovic, SF, Pippucci, T, Canafoglia, L, Bahlo, M, Striano, P, Scheffer, IE, Brancati, F, Depienne, C, Gecz, J, Corbett, MA, Kroes, T, Veneziano, L, Bennett, MF, Florian, R, Schneider, AL, Coppola, A, Licchetta, L, Franceschetti, S, Suppa, A, Wenger, A, Mei, D, Pendziwiat, M, Kaya, S, Delledonne, M, Straussberg, R, Xumerle, L, Regan, B, Crompton, D, van Rootselaar, A-F, Correll, A, Catford, R, Bisulli, F, Chakraborty, S, Baldassari, S, Tinuper, P, Barton, K, Carswell, S, Smith, M, Berardelli, A, Carroll, R, Gardner, A, Friend, KL, Blatt, I, Iacomino, M, Di Bonaventura, C, Striano, S, Buratti, J, Keren, B, Nava, C, Forlani, S, Rudolf, G, Hirsch, E, Leguern, E, Labauge, P, Balestrini, S, Sander, JW, Afawi, Z, Helbig, I, Ishiura, H, Tsuji, S, Sisodiya, SM, Casari, G, Sadleir, LG, van Coller, R, Tijssen, MAJ, Klein, KM, van den Maagdenberg, AMJM, Zara, F, Guerrini, R, Berkovic, SF, Pippucci, T, Canafoglia, L, Bahlo, M, Striano, P, Scheffer, IE, Brancati, F, Depienne, C, and Gecz, J
Abstract: Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involved.
Published: 2019

40. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author: Florian, RT, Kraft, F, Leitao, E, Kaya, S, Klebe, S, Magnin, E, van Rootselaar, A-F, Buratti, J, Kuehnel, T, Schroeder, C, Giesselmann, S, Tschernoster, N, Altmueller, J, lamiral, A, Keren, B, Nava, C, Bouteiller, D, Forlani, S, Jornea, L, Kubica, R, Ye, T, Plassard, D, Jost, B, Meyer, V, Deleuze, J-F, Delpu, Y, Avarello, MDM, Vijfhuizen, LS, Rudolf, G, Hirsch, E, Kroes, T, Reif, PS, Rosenow, F, Ganos, C, Vidailhet, M, Thivard, L, Mathieu, A, Bourgeron, T, Kurth, I, Rafehi, H, Steenpass, L, Horsthemke, B, Berkovic, SF, Bisulli, F, Brancati, F, Canafoglia, L, Casari, G, Guerrini, R, Ishiura, H, Licchetta, L, Mei, D, Pippucci, T, Sadleir, L, Scheffer, IE, Striano, P, Tinuper, P, Tsuji, S, Zara, F, LeGuern, E, Klein, KM, Labauge, P, Bennett, MF, Bahlo, M, Gecz, J, Corbett, MA, Tijssen, MAJ, van den Maagdenberg, AMJM, Depienne, C, Florian, RT, Kraft, F, Leitao, E, Kaya, S, Klebe, S, Magnin, E, van Rootselaar, A-F, Buratti, J, Kuehnel, T, Schroeder, C, Giesselmann, S, Tschernoster, N, Altmueller, J, lamiral, A, Keren, B, Nava, C, Bouteiller, D, Forlani, S, Jornea, L, Kubica, R, Ye, T, Plassard, D, Jost, B, Meyer, V, Deleuze, J-F, Delpu, Y, Avarello, MDM, Vijfhuizen, LS, Rudolf, G, Hirsch, E, Kroes, T, Reif, PS, Rosenow, F, Ganos, C, Vidailhet, M, Thivard, L, Mathieu, A, Bourgeron, T, Kurth, I, Rafehi, H, Steenpass, L, Horsthemke, B, Berkovic, SF, Bisulli, F, Brancati, F, Canafoglia, L, Casari, G, Guerrini, R, Ishiura, H, Licchetta, L, Mei, D, Pippucci, T, Sadleir, L, Scheffer, IE, Striano, P, Tinuper, P, Tsuji, S, Zara, F, LeGuern, E, Klein, KM, Labauge, P, Bennett, MF, Bahlo, M, Gecz, J, Corbett, MA, Tijssen, MAJ, van den Maagdenberg, AMJM, and Depienne, C
Abstract: Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
Published: 2019

41. Clinical features and long term outcome of epilepsy in periventricular nodular heterotopia. Simple compared with plus forms

Author: d’Orsi, G, Tinuper, P, Bisulli, F, Zaniboni, A, Bernardi, B, Rubboli, G, Riva, R, Michelucci, R, Volpi, L, Tassinari, C A, and Baruzzi, A
Published: 2004

42. Idiopathic partial epilepsy with auditory features (IPEAF): a clinical and genetic study of 53 sporadic cases

Author: Bisulli, F., Tinuper, P., Avoni, P., Striano, P., Striano, S., dʼOrsi, G., Vignatelli, L., Bagattin, A., Scudellaro, E., Florindo, I., Nobile, C., Tassinari, C. A., Baruzzi, A., and Michelucci, R.
Published: 2004

43. A clinical and genetic study of 33 new cases with early-onset absence epilepsy

Author: Giordano L, Vignoli A, Accorsi P, Galli J, Pezzella M, Traverso M, Battaglia S, Baglietto MG, Beccaria F, Cerminara C, Gambara S, Crichiutti G, Bisulli F, Pinci M, Tinuper P, Briatore E, Calzolari S, Coppola A, Canevini MP, Capovilla G, Zara F, Minetti C, Striano P., COPPOLA, ANTONIETTA, DEL GIUDICE, ENNIO, STRIANO, SALVATORE, Giordano L., Vignoli A., Accorsi P., Galli J., Pezzella M., Traverso M., Battaglia S., Baglietto M.G., Beccaria F., Cerminara C., Gambara S., Del Giudice E., Crichiutti G., Bisulli F., Pinci M., Tinuper P., Briatore E., Calzolari S., Coppola A., Canevini M.P., Capovilla G., Striano S., Zara F., Minetti C., Striano P., Giordano, L, Vignoli, A, Accorsi, P, Galli, J, Pezzella, M, Traverso, M, Battaglia, S, Baglietto, Mg, Beccaria, F, Cerminara, C, Gambara, S, DEL GIUDICE, Ennio, Crichiutti, G, Bisulli, F, Pinci, M, Tinuper, P, Briatore, E, Calzolari, S, Coppola, A, Canevini, Mp, Capovilla, G, Striano, Salvatore, Zara, F, Minetti, C, Striano, P., and Coppola, Antonietta
Subjects: Male, Pediatrics, medicine.medical_specialty, SLC2A1, DNA Mutational Analysis, Electroencephalography, Idiopathic generalized epilepsy, Epilepsy, Childhood absence epilepsy, Borderline intellectual functioning, Absence epilepsy, medicine, Humans, IGE, EEG, Age of Onset, Psychiatry, Early-onset, Retrospective Studies, Early onset, Glucose Transporter Type 1, medicine.diagnostic_test, business.industry, Infant, Retrospective cohort study, medicine.disease, Epilepsy, Absence, Italy, Neurology, Child, Preschool, Mutation, Female, Therapy, Neurology (clinical), Age of onset, business
Abstract: Summary Purpose To investigate the electroclinical features and the outcome of patients with typical absences starting before the 3 years of life. Methods We reviewed the clinical data of patients with absences started before 3 years observed over a 15-year period. Mutation analysis of SLC2A1 (GLUT-1) gene was performed when possible. Their clinical features were compared with those of subjects with a diagnosis of childhood absence epilepsy (CAE). Results Among 33 children with absence epilepsy starting before 3 years of life, there were 20 boys and 13 girls. Mean seizure onset was at 28.0±8.3 (range: 8–36) months of life. Two children displayed borderline intellectual functioning at long-term follow-up. Twenty-eight (85%) patients showed excellent response to therapy. Three subjects evolved into a different form of idiopathic generalized epilepsy (IGE). No SLC2A1 mutation was identified in 20 (60.6%) patients tested. The main clinical features of patients with early-onset absences did not differ from those of CAE except for increased prevalence of males ( p =0.002) and longer treatment duration ( p =0.001) in the former. Conclusions Strong similarities in the electroclinical features and outcome between children with early-onset absences and those with CAE support the view that these conditions are part of the wide spectrum of IGE.
Published: 2011

44. Ictal bradycardia in partial epileptic seizures: Autonomic investigation in three cases and literature review

Author: Tinuper, P., Bisulli, F., Cerullo, A., Carcangiu, R., Marini, C., Pierangeli, G., and Cortelli, P.
Published: 2001

45. Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study (Journal of Neuro-Oncology, (2016), 128, 1, (157-162), 10.1007/s11060-016-2093-1)

Author: Franceschi, Enrico, Depenni, Roberta, Paccapelo, Alexandro, Ermani, Mario, Faedi, Marina, Sturiale, Carmelo, Michiara, Maria, Servadei, Franco, Pavesi, Giacomo, Urbini, Benedetta, Pisanello, Anna, Crisi, Girolamo, Cavallo, Michele A., Dazzi, Claudio, Biasini, Claudia, Bertolini, Federica, Mucciarini, Claudia, Pasini, Giuseppe, Baruzzi, Agostino, Brandes, Alba A., Baruzzi, A., Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., Brandes, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Franceschi, E., Tosoni, A., Cavallo, Marino, Fiorica, F., Valentini, A., Depenni, R., Mucciarini, C., Crisi, G., Sasso, Enrico, Biasini, C., Cavanna, L., Guidetti, D., Marcello, Norina, Pisanello, A., Cremonini, A. M., Guiducci, G., de Pasqua, S., Testoni, S., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, Stefano, Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, Vincenzo, Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Faedi, M., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, Giuseppe, Cenni, P., Dazzi, C., Guidi, A. R., Zumaglini, F., Amadori, A., Pasini, G., Pasquinelli, Mario, Pasquini, Elena, Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, Greta, Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, Corrado, Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, Margherita, Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M. R., Urbini, B., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., and Nobile, C.
Subjects: Cancer Research, Oncology, Neurology, Neurology (clinical)
Published: 2018

46. Super refractory status epilepticus in Lafora disease interrupted by vagus nerve stimulation: A case report

Author: Mostacci, B., primary, Bisulli, F., additional, Muccioli, L., additional, Minardi, I., additional, Bandini, M., additional, Licchetta, L., additional, Zucchelli, M., additional, Leta, C., additional, Michelucci, R., additional, Zanello, M., additional, and Tinuper, P., additional
Published: 2019
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47. Videopolygraphic Semiological Promenade in and Around the "Negative Supplementary Motor Areas": Ictal Manifestations.

Author: Volpi, L., Rubboli, G., Rizzi, R., Bisulli, F., Gardella, E., Riguzzi, P., and Valzania, F.
Published: 1998

48. Epilepsy and Sleep: Close Connections and Reciprocal Influences

Author: Tinuper P., Bisulli F., Provini F., Marco Mula, Tinuper P., Bisulli F., and Provini F.
Subjects: epilepsy, sleep, arousal disorder, Noctural Frontal Lobe Seizures
Abstract: Epilepsy is a neurological condition that knows no geographic, social, or racial boundaries, occurring in men and women, affecting all ages, though more frequently affecting young people in the first two decades of life and people over the age of 60 years. It has been estimated that worldwide there are at least 50 million people who have epilepsy and more than 80% of people with epilepsy live in developing countries where the condition remains largely untreated. Epilepsy and epileptic seizures affect every aspect of a patient's cognitive, social, and emotional well-being. Also sleep disorders have an adverse impact on daily living for both patients and their caregivers.
Published: 2016

49. Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study

Author: Franceschi, Enrico, Depenni, R., Paccapelo, Alexandro, Ermani, Mario, Faedi, M., Sturiale, Carmelo, Michiara, Maria, Servadei, F., Pavesi, Giacomo, Urbini, B., Pisanello, A., Crisi, G., Cavallo, Michele A., Dazzi, C., Biasini, C., Bertolini, F., Mucciarini, C., Pasini, G., Baruzzi, Agostino, Brandes, Alba A, Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., de Pasqua, S., Testoni, S., Brandes, A., Franceschi, E., Tosoni, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Fiorica, F., Sasso, E., Cavanna, L., Guidetti, D., Marcello, N., Cremonini, A. M., Guiducci, G., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Guidi, A. R., Zumaglini, F., Amadori, A., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, Stefano, Nichelli, Paolo Frigio, Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, M., Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M. R., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Silini, E. M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., Nobile, C., Franceschi, E., Depenni, R., Paccapelo, Alexandro, Ermani, Mario, Faedi, M., Sturiale, Carmelo, Michiara, Maria, Servadei, F., Pavesi, Giacomo, Urbini, B., Pisanello, A., Crisi, G., Cavallo, Michele A., Dazzi, C., Biasini, C., Bertolini, F., Mucciarini, C., Pasini, G., Baruzzi, Agostino, Brandes, Alba A., Albani, F., Calbucci, F., D’Alessandro, R., Michelucci, R., de Pasqua, S., Testoni, S., Brandes, A., Tosoni, A., Eusebi, V., Ceruti, S., Fainardi, E., Tamarozzi, R., Emiliani, E., Cavallo, M., Fiorica, F., Sasso, E., Cavanna, L., Guidetti, D., Marcello, N., Cremonini, A.M., Guiducci, G., Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., Dall’Agata, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A., Strumia, S., Casmiro, M., Gamboni, A., Rasi, F., Cruciani, G., Cenni, P., Guidi, A.R., Zumaglini, F., Amadori, A., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., Viti, B., Sintini, M., Ariatti, A., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., Zunarelli, E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., Stucchi, C., Iaccarino, C., Ragazzi, M., Rizzi, R., Zuccoli, G., Api, P., Cartei, F., Colella, M., Fallica, E., Farneti, M., Frassoldati, A., Granieri, E., Latini, F., Monetti, C., Saletti, A., Schivalocchi, R., Sarubbo, S., Seraceni, S., Tola, M.R., Zini, G., Giorgi, C., Montanari, E., Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Silini, E.M., Torelli, P., Immovilli, P., Morelli, N., Vanzo, C., and Nobile, C.
Subjects: Oncology, medicine.medical_specialty, Cancer Research, medicine.medical_treatment, Dacarbazine, Population, Context (language use), NO, 03 medical and health sciences, 0302 clinical medicine, Elderly, Internal medicine, medicine, Temozolomide, Humans, MGMT methylation, Prospective Studies, Prospective cohort study, education, Promoter Regions, Genetic, Antineoplastic Agents, Alkylating, DNA Modification Methylases, Survival analysis, Aged, Aged, 80 and over, education.field_of_study, Radiotherapy, business.industry, Brain Neoplasms, Tumor Suppressor Proteins, Glioblastoma, Neurology (clinical), Neurology, DNA Methylation, Survival Analysis, Surgery, Radiation therapy, DNA Repair Enzymes, 030220 oncology & carcinogenesis, Concomitant, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly patients with glioblastoma (GBM) remains unclear. We evaluated the outcome of patients >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. For this analysis the criteria for selecting patients enrolled in the PERNO study were: age >70 years; PS 0–3; histologically confirmed GBM; postoperative radiotherapy (RT) after surgery with or without concomitant temozolomide (TMZ) or postsurgical TMZ alone. Between January 2009 and December 2010, 76 GBM elderly patients were identified in the prospective PERNO study. Twenty-three patients did not receive any treatment after surgery, and 53 patients received postsurgical treatments (25 patients received RT alone and 28 patients RT/TMZ). Median survival was 11.1 months (95 % CI 8.8–13.5), adding temozolomide concomitant and adjuvant to radiotherapy it was 11.6 months (95 % CI 8.6–14.6), and 9.3 months (95 % CI 8.1–10.6) in patients treated with RT alone (P = 0.164). However, patients with MGMT methylated treated with RT/TMZ obtained a better survival (17.2 months, 95 % CI 11.5–22.9) (P = 0.042). No difference in terms of survival were observed if patients with MGMT unmethylated tumor received RT alone, or RT/TMZ or, in MGMT methylated tumor, if patients received radiotherapy alone. In elderly patients RT/TMZ represent a widely used approach but it is effective with methylated MGMT tumors only.
Published: 2016

50. Erratum to: Incidence of neuroepithelial primary brain tumors among adult population of Emilia-Romagna Region, Italy

Author: Baldin, E, Testoni, S, de Pasqua, S, Ferro, S, Albani, F, Baruzzi, A, D'Alessandro, R, PERNO study group Participants: Agati, R., Ambrosetto, G., Bacci, A., Baldin, E., Baldrati, A., Barbieri, E., Bartolini, S., Bellavista, E., Bisulli, F., Bonora, E., Bunkheila, F., Carelli, V., Cerasoli, S., Crisci, M., Dall’Occa, P., de Biase, D., Ferro, S., Franceschi, C., Frezza, G., Grasso, V., Leonardi, M., Marucci, G., Morandi, L., Mostacci, B., Palandri, G., Pasini, E., Pastore Trossello, M., Pession, A., Poggi, R., Riguzzi, P., Rinaldi, R., Rizzi, S., Romeo, G., Spagnolli, F., Tinuper, P., Trocino, C., (Bologna), Visani M., Dall’Agata, M., Faedi, M., Frattarelli, M., Gentili, G., Giovannini, A., Iorio, P., Pasquini, U., Galletti, G., Guidi, C., Neri, W., Patuelli, A. ., (ForlI´-Cesena), Strumia S., Casmiro, M., Gamboni, A., (Faenza, Rasi F., RA), (Lugo, Cruciani G., Cenni, P., Dazzi, C., Guidi, A. R., (Ravenna), Zumaglini F., Amadori, A., Pasini, G., Pasquinelli, M., Pasquini, E., Polselli, A., Ravasio, A., (Rimini), Viti B., (Cattolica, Sintini M., RN), Ariatti, A., Bertolini, F., Bigliardi, G., Carpeggiani, P., Cavalleri, F., Meletti, S., Nichelli, P., Pettorelli, E., Pinna, G., (Modena), Zunarelli E., Artioli, F., Bernardini, I., Costa, M., Greco, G., Guerzoni, R., (Carpi, Stucchi C., MO), Iaccarino, C, Ragazzi, M., Rizzi, R., (Reggio Emilia), Zuccoli G., Api, P., Cartei, F., Fallica, E., Granieri, E., Latini, F., Lelli, G., Monetti, C., Saletti, A., Schivalocchi, R., Seraceni, S., Tola, M. R., (Ferrara), Urbini B., Giorgi, C., (Fidenza, Montanari E., PR), Cerasti, D., Crafa, P., Dascola, I., Florindo, I., Giombelli, E., Mazza, S., Ramponi, V., Servadei, F., Silini, Em., (Parma), Torelli P., Immovilli, P., Morelli, N., (Piacenza), Vanzo C., Nobile, C. (Padova)., Elisa Baldin, Stefania Testoni, Silvia de Pasqua, Salvatore Ferro, Fiorenzo Albani, Agostino Baruzzi, Roberto D’Alessandro, On behalf of PERNO study group, ELENA BONORA, and DARIO DE BIASE
Subjects: Psychiatry and Mental Health, Dermatology, General Medicine, Neurology (clinical)
Abstract: Unfortunately, some of the participants of the PERNO Study Group are missing in the original publication of the article. The correct details are given below: Participants: Agati R., Ambrosetto G., Bacci A., Baldin E., Baldrati A., Barbieri E., Bartolini S., Bellavista E., Bisulli F., Bonora E., Bunkheila F., Carelli V., Cerasoli S., Crisci M., Dall’Occa P., de Biase D., Ferro S., Franceschi C., Frezza G., GrassoV., Leonardi M., Marucci G., Morandi L., Mostacci B., Palandri G., Pasini E., Pastore Trossello M., Pession A., Poggi R., Riguzzi P., Rinaldi R., Rizzi S., Romeo G., Spagnolli F., Tinuper P., Trocino C., Visani M. (Bologna), Dall’Agata M., Faedi M., Frattarelli M., Gentili G., Giovannini A., Iorio P., Pasquini U., Galletti G., Guidi C., Neri W., Patuelli A.., Strumia S. (ForlÍ-Cesena), Casmiro M., Gamboni A., Rasi F. (Faenza, RA), Cruciani G. (Lugo, RA), Cenni P., Dazzi C., Guidi A.R., Zumaglini F. (Ravenna), Amadori A., Pasini G., Pasquinelli M., Pasquini E., Polselli A., Ravasio A., Viti B. (Rimini), Sintini M. (Cattolica, RN), Ariatti A., Bertolini F., Bigliardi G., Carpeggiani P., Cavalleri F., Meletti S., Nichelli P., Pettorelli E., Pinna G., Zunarelli E. (Modena), Artioli F., Bernardini I., Costa M., Greco G., Guerzoni R., Stucchi C. (Carpi, MO), Iaccarino C., Ragazzi M., Rizzi R., Zuccoli G. (Reggio Emilia), Api P., Cartei F., Fallica E., Granieri E., Latini F., Lelli G., Monetti C., Saletti A., Schivalocchi R., Seraceni S., Tola M.R., Urbini B. (Ferrara), Giorgi C., Montanari E. (Fidenza, PR), Cerasti D., Crafa P., Dascola I., Florindo I., Giombelli E., Mazza S., Ramponi V., Servadei F., Silini EM., Torelli P. (Parma), Immovilli P., Morelli N., Vanzo C. (Piacenza), Nobile C. (Padova).
Published: 2017

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