{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:20:47Z","timestamp":1781191247763,"version":"3.54.1"},"reference-count":19,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were females) who attended the Neurology and Nephrology Clinics of Fundeni Clinical Institute in Romania from 2015 to 2020. Seventeen patients were diagnosed with epilepsy, nine patients had intellectual impairment, and complete neuroimaging was available for twenty-two patients. As expected, the most frequent dermatological lesions were cutaneous angiofibromas in 20 patients, but with a lower frequency than described in the current literature. Statistical analysis was performed considering the small number of patients. Cortical tubers in neuroimaging seemed to be associated with the diagnosis of epilepsy, while subependymal nodules represented a risk factor for intellectual impairment. Males showed a larger number of dermatological types of lesions, especially caf\u00e9 -au-lait patches. Interestingly, we found a statistically significant positive association between epilepsy and the presence of cutaneous angiofibromas, as well as total dermatological involvement. Females had significantly higher Charlson comorbidity index scores, indicating a higher burden of disease. Everolimus seemed to be a well-tolerated treatment and showed promising results in controlling epileptic seizures alone in two patients. More studies, with the inclusion of a larger number of patients, are needed to confirm these results.<\/jats:p>","DOI":"10.3390\/jcm12206550","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T08:32:57Z","timestamp":1697445177000},"page":"6550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neurological and Dermatological Manifestations of Tuberous Sclerosis Complex: Report from a Romanian Tertiary Hospital Cohort"],"prefix":"10.3390","volume":"12","author":[{"given":"Adriana Octaviana","family":"Dulamea","sequence":"first","affiliation":[{"name":"Neurology Clinic, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Department III, Dental Medicine Faculty, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9500-4498","authenticated-orcid":false,"given":"Anca Adriana","family":"Arbune","sequence":"additional","affiliation":[{"name":"Neurology Clinic, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Anghel","sequence":"additional","affiliation":[{"name":"Neurology Clinic, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Department III, Dental Medicine Faculty, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voicu","family":"Boscaiu","sequence":"additional","affiliation":[{"name":"Institute of Mathematical Statistics and Applied Mathematics \u201cGheorghe Mihoc-Caius Iacob\u201d, 050711 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5590-7879","authenticated-orcid":false,"given":"Andreea","family":"Andronesi","sequence":"additional","affiliation":[{"name":"Nephrology Clinic, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Department 3, Medicine Faculty, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gener","family":"Ismail","sequence":"additional","affiliation":[{"name":"Nephrology Clinic, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Department 3, Medicine Faculty, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S1474-4422(15)00069-1","article-title":"Neurological and Neuropsychiatric Aspects of Tuberous Sclerosis Complex","volume":"14","author":"Curatolo","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16035","DOI":"10.1038\/nrdp.2016.35","article-title":"Tuberous Sclerosis Complex","volume":"2","author":"Henske","year":"2016","journal-title":"Nat. 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Rare Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13023-016-0553-5","article-title":"TuberOus SClerosis Registry to Increase Disease Awareness (TOSCA)\u2014Baseline Data on 2093 Patients","volume":"12","author":"Kingswood","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jaad.2007.05.004","article-title":"Tuberous Sclerosis Complex: Advances in Diagnosis, Genetics, and Management","volume":"57","author":"Schwartz","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1046\/j.1365-4362.1998.00495.x","article-title":"Skin Lesions in Children with Tuberous Sclerosis Complex: Their Prevalence, Natural Course, and Diagnostic Significance","volume":"37","author":"Schwartz","year":"1998","journal-title":"Int. J. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0140-6736(12)61134-9","article-title":"Efficacy and Safety of Everolimus for Subependymal Giant Cell Astrocytomas Associated with Tuberous Sclerosis Complex (EXIST-1): A Multicentre, Randomised, Placebo-Controlled Phase 3 Trial","volume":"381","author":"Franz","year":"2013","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0140-6736(12)61767-X","article-title":"Everolimus for Angiomyolipoma Associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis (EXIST-2): A Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial","volume":"381","author":"Bissler","year":"2013","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/S0140-6736(16)31419-2","article-title":"Adjunctive Everolimus Therapy for Treatment-Resistant Focal-Onset Seizures Associated with Tuberous Sclerosis (EXIST-3): A Phase 3, Randomised, Double-Blind, Placebo-Controlled Study","volume":"388","author":"French","year":"2016","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13023-017-0596-2","article-title":"MTOR Inhibitors in the Pharmacologic Management of Tuberous Sclerosis Complex and Their Potential Role in Other Rare Neurodevelopmental Disorders","volume":"12","author":"Franz","year":"2017","journal-title":"Orphanet J. 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Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1001\/jamadermatol.2014.938","article-title":"Dermatologic and Dental Aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements","volume":"150","author":"Teng","year":"2014","journal-title":"JAMA Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1136\/archdischild-2016-312001","article-title":"Cutaneous Manifestations of Tuberous Sclerosis Complex and the Paediatrician\u2019s Role","volume":"102","author":"Cardis","year":"2017","journal-title":"Arch. Dis. Child."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A New Method of Classifying Prognostic Comorbidity in Longitudinal Studies: Development and Validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. 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