A Multinational Survey on Actual Diagnostics and Treatment of Subacute Sclerosing Panencephalitis

Martin Häusler; Ayse Aksoy; Michael Alber; Sakir Altunbasak; Aydan Angay; Oana Tarta Arsene; Dana Craiu; Hans Hartmann; Semra Hiz-Kurul; Takashi Ichiyama; Catrinel Iliescu; Bosanka Jocic-Jakubi; Rudolf Korinthenberg; Gülsen Köse; Marissa B. Lukban; Mehpare Ozkan; Iliyana Patcheva; Jens Teichler; Mihaela Vintan; Ahmet Yaramis; Coskun Yarar; Uluc Yis; Deniz Yuksel; Banu Anlar

doi:10.1055/s-0035-1564618

Neuropediatrics, Table of Contents

Neuropediatrics 2015; 46(06): 377-384
DOI: 10.1055/s-0035-1564618

Original Article

Georg Thieme Verlag KG Stuttgart · New York

A Multinational Survey on Actual Diagnostics and Treatment of Subacute Sclerosing Panencephalitis

Martin Häusler

¹Division of Pediatric Neurology and Social Pediatrics, Department of Pediatrics, University Hospital RWTH Aachen, Aachen, Germany

,

Ayse Aksoy

²Clinics of Pediatric Neurology, Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases, Ankara, Turkey

,

Michael Alber

³Department of Neuropaediatrics, University Children's Hospital, Tübingen, Germany

,

Sakir Altunbasak

⁴Department of Pediatric Neurology, Cukurova University, Faculty of Medicine, Saricam/Adana, Turkey

,

Aydan Angay

⁵Private Practice, Göztepe, Istanbul, Turkey

,

Oana Tarta Arsene

⁶Pediatric Neurology Clinic, Professor Doctor Alexandru Obregia Clinical Hospital, Bucharest, Romania

,

Dana Craiu

⁶Pediatric Neurology Clinic, Professor Doctor Alexandru Obregia Clinical Hospital, Bucharest, Romania

⁷Department of Neurology, Pediatric Neurology, Psychiatry, Neurosurgery, Pediatric Neurology Clinic II, Carol Davila University of Medicine, Bucharest, Romania

,

Hans Hartmann

⁸Department of Pediatrics, Hannover Medical School, Hannover, Germany

,

Semra Hiz-Kurul

⁹Division of Child Neurology, Department of Pediatrics, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey

,

Takashi Ichiyama

¹⁰Department of Pediatrics, Tsudumigaura Handicapped Children's Hospital, Yamaguchi, Japan

,

Catrinel Iliescu

⁶Pediatric Neurology Clinic, Professor Doctor Alexandru Obregia Clinical Hospital, Bucharest, Romania

⁷Department of Neurology, Pediatric Neurology, Psychiatry, Neurosurgery, Pediatric Neurology Clinic II, Carol Davila University of Medicine, Bucharest, Romania

,

Bosanka Jocic-Jakubi

¹¹Department of Pediatric Neurology, Clinical Center Nis, Pediatric Clinic, Nis, Serbia

¹²Department of Pediatrics, Al Sabah Hospital, Kuwait

,

Rudolf Korinthenberg

¹³Division of Neuropediatrics and Muscular Diseases, Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Gülsen Köse

¹⁴Department of Child Neurology, Health Ministery Şişli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey

,

Marissa B. Lukban

¹⁵Manila Department of Pediatrics and Neurosciences, University of the Philippines College of Medicine, Manila, Philippines

,

Mehpare Ozkan

²Clinics of Pediatric Neurology, Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases, Ankara, Turkey

,

Iliyana Patcheva

¹⁶Department of Pediatrics and Medical Genetics, Medical University-Plovdiv, Plovdiv, Bulgaria

,

Jens Teichler

¹⁷Department of Neuropediatrics, University Children's Hospital Zurich, Zürich, Switzerland

¹⁸Department of Social Pediatrics, Konstanz General Hospital, Konstanz, Germany

,

Mihaela Vintan

¹⁹Department of Neuroscience, Faculty of medicine, University of Medicine and Pharmacy, Cluj Napoca, Romania

,

Ahmet Yaramis

²⁰Pediatric Neurology Department, Dicle University, Diyarbakır, Turkey

,

Coskun Yarar

²¹Child Neurology Unit, Eskisehir Osmangazi University, Eskisehir, Turkey

,

Uluc Yis

⁹Division of Child Neurology, Department of Pediatrics, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey

,

Deniz Yuksel

²Clinics of Pediatric Neurology, Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases, Ankara, Turkey

,

Banu Anlar

²²Department of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey

› Author Affiliations

Abstract

Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system caused by the measles virus (MV). Its prevalence remains high in resource poor countries and is likely to increase in the Northern Europe as vaccination rates decrease. Clinical knowledge of this devastating condition, however, is limited. We therefore conducted this multinational survey summarizing experience obtained from more than 500 patients treated by 24 physicians in seven countries. SSPE should be considered in all patients presenting with otherwise unexplained acquired neurological symptoms. In most patients, the diagnosis will be established by the combination of typical clinical symptoms (characteristic repetitive myoclonic jerks), a strong intrathecal synthesis of antibodies to MV and typical electroencephalogram findings (Radermecker complexes). Whereas the therapeutic use of different antiviral (amantadine, ribavirin) and immunomodulatory drugs (isoprinosine, interferons) and of immunoglobulins has been reported repeatedly, optimum application regimen of these drugs has not been established. This is partly due to the absence of common diagnostic and clinical standards focusing on neurological and psychosocial aspects. Carbamazepine, levetiracetam, and clobazam are the drugs most frequently used to control myoclonic jerks. We have established a consensus on essential laboratory and clinical parameters that should facilitate collaborative studies. Those are urgently needed to improve outcome.

Keywords

subacute sclerosing panencephalitis - measles virus - interferon - isoprinosine - ribavirin - amantadine

Full Text

References

References
1 Anlar B, Yalaz K. Prognosis in subacute sclerosing panencephalitis. Dev Med Child Neurol 2011; 53 (10) 965
2 Schneider-Schaulies J, Meulen Vt, Schneider-Schaulies S. Measles infection of the central nervous system. J Neurovirol 2003; 9 (2) 247-252
3 Schneider-Schaulies J, Schnorr JJ, Brinckmann U , et al. Receptor usage and differential downregulation of CD46 by measles virus wild-type and vaccine strains. Proc Natl Acad Sci U S A 1995; 92 (9) 3943-3947
4 Schneider-Schaulies J, ter Meulen V, Schneider-Schaulies S. Measles virus interactions with cellular receptors: consequences for viral pathogenesis. J Neurovirol 2001; 7 (5) 391-399
5 Watanabe A, Yoneda M, Ikeda F, Terao-Muto Y, Sato H, Kai C. CD147/EMMPRIN acts as a functional entry receptor for measles virus on epithelial cells. J Virol 2010; 84 (9) 4183-4193
6 Tanaka J, Nakamura H, Fukada T. Adult-onset subacute sclerosing panencephalitis: immunocytochemical and electron microscopic demonstration of the viral antigen. Clin Neuropathol 1987; 6 (1) 30-37
7 Jiang DP, Ide YH, Nagano-Fujii M, Shoji I, Hotta H. Single-point mutations of the M protein of a measles virus variant obtained from a patient with subacute sclerosing panencephalitis critically affect solubility and subcellular localization of the M protein and cell-free virus production. Microbes Infect 2009; 11 (4) 467-475
8 Patterson JB, Cornu TI, Redwine J , et al. Evidence that the hypermutated M protein of a subacute sclerosing panencephalitis measles virus actively contributes to the chronic progressive CNS disease. Virology 2001; 291 (2) 215-225
9 Lawrence DM, Patterson CE, Gales TL, D'Orazio JL, Vaughn MM, Rall GF. Measles virus spread between neurons requires cell contact but not CD46 expression, syncytium formation, or extracellular virus production. J Virol 2000; 74 (4) 1908-1918
10 Palosaari H, Parisien JP, Rodriguez JJ, Ulane CM, Horvath CM. STAT protein interference and suppression of cytokine signal transduction by measles virus V protein. J Virol 2003; 77 (13) 7635-7644
11 Ishizaki Y, Takemoto M, Kira R , et al. Association of toll-like receptor 3 gene polymorphism with subacute sclerosing panencephalitis. J Neurovirol 2008; 14 (6) 486-491
12 Pipo-Deveza JR, Kusuhara K, Silao CL , et al. Analysis of MxA, IL-4, and IRF-1 genes in Filipino patients with subacute sclerosing panencephalitis. Neuropediatrics 2006; 37 (4) 222-228
13 Yentur SP, Aydin HN, Gurses C , et al. Granzyme B gene polymorphism associated with subacute sclerosing panencephalitis. Neuropediatrics 2014; 45 (5) 309-313
14 Anlar B, Söylemezoğlu F, Aysun S, Köse G, Belen D, Yalaz K. Tissue inflammatory response in subacute sclerosing panencephalitis (SSPE). J Child Neurol 2001; 16 (12) 895-900
15 Anlar B, Söylemezoğlu F, Elibol B , et al. Apoptosis in brain biopsies of subacute sclerosing panencephalitis patients. Neuropediatrics 1999; 30 (5) 239-242
16 Thurner B, Spangenberg P, Kleines M, Blaum M, Scheithauer S, Häusler M. Continuous intrathecal interferon alpha application in subacute sclerosing panencephalitis. Pediatr Infect Dis J 2007; 26 (9) 863
17 Wirguin I, Vander T, Brenner T, Abramsky O, Steiner I. Improvement of SSPE by intrathecal infusion of alpha-IFN. Neurology 2005; 64 (2) 402 , author reply 402
18 Aydin OF, Senbil N, Kuyucu N, Gürer YK. Combined treatment with subcutaneous interferon-alpha, oral isoprinosine, and lamivudine for subacute sclerosing panencephalitis. J Child Neurol 2003; 18 (2) 104-108
19 Anlar B, Aydin OF, Guven A, Sonmez FM, Kose G, Herguner O. Retrospective evaluation of interferon-beta treatment in subacute sclerosing panencephalitis. Clin Ther 2004; 26 (11) 1890-1894
20 Fukuyama Y, Nihei K, Matsumoto S , et al. Clinical effects of MND-19 (Inosiplex) on subacute sclerosing panencephalitis—a multi-institutional collaborative study—The Inosiplex-SSPE Research Committee. Brain Dev 1987; 9 (3) 270-282
21 Jones CE, Dyken PR, Huttenlocher PR, Jabbour JT, Maxwell KW. Inosiplex therapy in subacute sclerosing panencephalitis. A multicentre, non-randomised study in 98 patients. Lancet 1982; 1 (8280) 1034-1037
22 Gascon GG ; International Consortium on Subacute Sclerosing Panencephalitis. Randomized treatment study of inosiplex versus combined inosiplex and intraventricular interferon-alpha in subacute sclerosing panencephalitis (SSPE): international multicenter study. J Child Neurol 2003; 18 (12) 819-827
23 Tomoda A, Nomura K, Shiraishi S , et al. Trial of intraventricular ribavirin therapy for subacute sclerosing panencephalitis in Japan. Brain Dev 2003; 25 (7) 514-517
24 Solomon T, Hart CA, Vinjamuri S, Beeching NJ, Malucci C, Humphrey P. Treatment of subacute sclerosing panencephalitis with interferon-alpha, ribavirin, and inosiplex. J Child Neurol 2002; 17 (9) 703-705
25 Lukban MB, Chua-Macrohon BC, Salonga AM. The Use of Intravenous Immunoglobulin in Subacute Sclerosing Panencephalitis: A Retrospective Cohort Study. Acta Med Philipp 2013; •••: 47
26 Makhortova NR, Askovich P, Patterson CE, Gechman LA, Gerard NP, Rall GF. Neurokinin-1 enables measles virus trans-synaptic spread in neurons. Virology 2007; 362 (1) 235-244
27 Oldstone MB, Dales S, Tishon A, Lewicki H, Martin L. A role for dual viral hits in causation of subacute sclerosing panencephalitis. J Exp Med 2005; 202 (9) 1185-1190
28 Dyken P, Dotson P, Maertens P. The neurological disability index (NDI) in subacute sclerosing panencephalitis (SSPE). In: Bergamini F, Defanti C, Ferrante P, eds. Subacute Sclerosing Panencephalitis: A Reappraisal. Amsterdam, Bergamo: Elsevier Science; 1986: 109-117
29 Anlar B, Yalaz K. Measles virus infection and subacute sclerosing panencephalitis. In: Jackson A, ed. Viral Infections of the Human Nervous System. Basel: Springer; 2013: 1-22
30 Ravikumar S, Crawford JR. Role of carbamazepine in the symptomatic treatment of subacute sclerosing panencephalitis: a case report and review of the literature. Case Rep Neurol Med 2013; 2013: 327647
31 Yiğit A, Sarikaya S. Myoclonus relieved by carbamazepine in subacute sclerosing panencephalitis. Epileptic Disord 2006; 8 (1) 77-80
32 Chakor RT, Santosh NS. Subacute sclerosing panencephalitis presenting as rapidly progressive young-onset dementia. J Pak Med Assoc 2013; 63 (7) 921-924
33 Garg RK, Anuradha HK, Varma R, Singh MK, Sharma PK. Initial clinical and radiological findings in patients with SSPE: are they predictive of neurological outcome after 6 months of follow-up?. J Clin Neurosci 2011; 18 (11) 1458-1462
34 Yimenicioglu S, Yakut A, Erol N, Carman K, Ekici A. Chorioretinitis as a first sign of SSPE. Neuropediatrics 2012; 43 (3) 149-151
35 Jacobi C, Lange P, Reiber H. Quantitation of intrathecal antibodies in cerebrospinal fluid of subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis: discrimination between microorganism-driven and polyspecific immune response. J Neuroimmunol 2007; 187 (1–2) 139-146
36 Cece H, Tokay L, Yildiz S, Karakas O, Karakas E, Iscan A. Epidemiological findings and clinical and magnetic resonance presentations in subacute sclerosing panencephalitis. J Int Med Res 2011; 39 (2) 594-602
37 Demir N, Cokar O, Bolukbasi F , et al. A close look at EEG in subacute sclerosing panencephalitis. J Clin Neurophysiol 2013; 30 (4) 348-356
38 Oztürk A, Gürses C, Baykan B, Gökyigit A, Eraksoy M. Subacute sclerosing panencephalitis: clinical and magnetic resonance imaging evaluation of 36 patients. J Child Neurol 2002; 17 (1) 25-29
39 Gokcil Z, Odabasi Z, Demirkaya S, Eroglu E, Vural O. Alpha-interferon and isoprinosine in adult-onset subacute sclerosing panencephalitis. J Neurol Sci 1999; 162 (1) 62-64
40 Gascon G, Yamani S, Crowell J , et al. Combined oral isoprinosine-intraventricular alpha-interferon therapy for subacute sclerosing panencephalitis. Brain Dev 1993; 15 (5) 346-355

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