Tuberous sclerosis complex, Serbian referral center experience

Ana Kosac; Nebojsa Jovic

doi:10.2298/VSP170410170K

Ana Kosac Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia
Nebojsa Jovic Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP170410170K

Ključne reči: skleroza, tuberozna, epilepsija, dijagnoza, lečenje lekovima, srbija

Sažetak

Apstrakt

Uvod/Cilj. Karakteristike kompleksa tuberozne skleroze uzrokovane su formiranjem hamartoma u mozgu i velikom broju organa, najčešće kao posledice mutacije u jednom od dva gena, TSC1 ili TSC2, sa veoma dobro dokumentovanom inter- i intrafamilijarnom razlikom u fenotipu. Cilj ovog rada bio je da se sintetišu podaci o bolesnicima sa dijagnostikovanom tuberoznom sklerozom radi boljeg razumevanja bolesti u našem okuženju. Metode. Retrospektivno je analizirana medicinska dokumentacija svih bolesnika sa kompleksom tuberozne skleroze, dijagnostikovanih i lečenih u Klinici za neurologiju i psihijatriju za decu i omladinu u Beogradu, Srbija, tokom vremenskog perioda dužeg od dve decenije. Statistička analiza sprovedena je merama deskriptivne statistike, kao i upotrebom Fišerovog testa. Rezultati. Analizirana je kohorta od 44 bolesnika sa dijagnozom definitivnog kompleksa tuberozne skleroze. Srednja vrednost životnog doba na poslednjem pregledu bila je 19.4 godine [uz raspon godina 1–58, standardna devijacija (SD) 11,8 godine]. Porodična pojava bolesti zabeležena je kod 25% bolesnika. Dermatološke manifestacije opisane su kod 93,2%, retinalni astrocitomi i rabdomiomi srca nađeni su kod po 36,4%, nefrološke manifestacije kod 34,1%, dok je limfangioleiomiomatoza dijagnostikovana kod dve bolesnice. Svi bolesnici su imali strukturne lezije centralnog nervnog sistema; epilepsija je dijagnostikovana kod 88,6% bolesnika, od kojih se kod 59% bolesnika prvi napad javio u prvoj godini života. Westov sindrom dijagnostikovan je kod 27,3% bolesnika. Potpuna kontrola epileptičkih napada postignuta je kod 30,8% bolesnika, u većini upotrebom valproične kiseline ili karbamazepina, ali i topiramata, lamotrigina i vigabatrina. Kod 82% bolesnika primenjena su najmanje dva antiepileptika. Mentalna retardacija je utvrđena kod 50% bolesnika. Psihijatrijske manifestacije bolesti bile su zapažene kod 40,9% bolesnika, od čega je poremećaj pažnje i hiperaktivnosti dijagnostikovan kod 27,3%, spektar autističnih poremećaja kod 13,6%, psihoza i depresija kod po 11,4% bolesnika. Zaključak. Sačinjena sinteza podataka doprinosi boljem razumevanju bolesti u našem okruženju, jer kompleks tuberozne skleroze, iako dobro definisano oboljenje, i dalje predstavlja dijagnostički i terapijski izazov u svakodnevnoj kliničkoj praksi.

Reference

REFERENCES

Northrup H, Krueger DA. Tuberous Sclerosis Complex Diagnos¬tic Criteria Update: Recommendations of the 2012 Interna¬tional Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49(4): 243–54.

Jentarra GM, Rice SG, Olfers S, Saffen D, Narayanan V. Ev-idence for population variation in TSC1 and TSC2 gene expression. BMC Med Genet 2011; 12: 29.

Wong M. Mechanisms of epileptogenesis in tuberous sclerosis complex and related malformations of cortical development with abnormal glioneuronal proliferation. Epilepsia 2008; 49(1): 8–21.

Muzykewicz DA, Costello DJ, Halpern EF, Thiele EA. Infantile spasms in tuberous sclerosis complex: Prognostic utility of EEG. Epilepsia 2009; 50(2): 290–6.

Bombardieri R, Pinci M, Moavero R, Cerminara C, Curatolo P. Early control of seizures improves long-term outcome in children with tuberous sclerosis complex. Eur J Paediatr Neurol 2010; 14(2): 146–9.

Cusmai R, Moavero R, Bombardieri R, Vigevano F, Curatolo P. Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis. Epilepsy Behav 2011; 22(4): 735–9.

Krueger DA. Management of CNS-related Disease Manifesta-tions in Patients With Tuberous Sclerosis Complex. Curr Treat Options Neurol 2013; 15(5): 618–33.

French JA, Lawson JA, Yapici Z, Ikeda H, Polster T, Nabbout R, et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): A phase 3, randomised, double-blind, placebo-controlled study. Lancet 2016; 388(10056): 2153–63.

Vries PJ, Whittemore VH, Leclezio L, Byars AW, Dunn D, Ess KC, et al. Tuberous sclerosis associated neuropsychiatric dis-orders (TAND) and the TAND Checklist. Pediatr Neurol 2015; 52(1): 25–35.

Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis com¬plex. N Engl J Med 2006; 355(13): 1345–56.

Roth J, Roach SE, Bartels U, Jóźwiak S, Koenig MK, Weiner HL, et al. Subependymal giant cell astrocytoma: Diagnosis, screening, and treatment. Recommendations from the International Tu¬berous Sclerosis Complex Consensus Conference 2012. Pedi¬atr Neurol 2013; 49(6): 439–44.

Thiele E, Korf B. Phakomatosis and allied conditions. In: Swai-man K, Ashwal S, Ferriero D, Schor N, editors. Swaiman's pediat¬ric neurology: Principles and Practice. 5th ed. New York, NY: Elsevier Inc; 2012. p. 497–517.

Jóźwiak S, Kotulska K, Kasprzyk-Obara J, Domańska-Pakieła D, To¬myn-Drabik M, Roberts P, et al. Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis com-plex. Pediatrics 2006; 118(4): 1146–51.

Wataya-Kaneda M, Tanaka M, Hamasaki T, Katayama I. Trends in the prevalence of tuberous sclerosis complex manifesta-tions: An epidemiological study of 166 Japanese patients. PLoS ONE 2013; 8(5): e63910.

Johnson SR, Whale CI, Hubbard RB, Lewis SA, Tattersfield AE. Sur¬vival and disease progression in UK patients with lym-phangioleiomyomatosis. Thorax 2004; 59(9): 800–3.

Joinson C, O'Callaghan FJ, Osborne JP, Martyn C, Harris T, Bolton PF. Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med 2003; 33(2): 335–44.

Winterkorn EB, Pulsifer MB, Thiele EA. Cognitive prognosis of patients with tuberous sclerosis complex. Neurology 2007; 68(1): 62–4.

Staley BA, Vail EA, Thiele EA. Tuberous sclerosis complex: Di¬agnostic challenges, presenting symptoms, and commonly missed signs. Pediatrics 2011; 127(1): 117–25.

Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 2010; 51(7): 1236–41.

D'Agati ED, Moavero R, Cerminara C, Curatolo P. Attention-defi¬cit hyperactivity disorder (ADHD) and tuberous sclerosis complex. J Child Neurol 2009; 24(10): 1282–7.

Curatolo P, Porfirio MC, Manzi B, Seri S. Autism in tuberous scle¬rosis. Eur J Paediatr Neurol 2004; 8(6): 327–32.

Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet 2008; 372(9639): 657–68.

Kothare SV, Singh K, Hochman T, Chalifoux JR, Staley BA, Weiner HL, et al. Genotype/phenotype in tuberous sclerosis complex: Associations with clinical and radiologic manifestations. Epi¬lepsia 2014; 55(7): 1020–4.

Kompleks tuberozne skleroze – kliničko iskustvo jednog referentnog centra u Srbiji

Sažetak

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