Paraneoplastic Neurologic Syndromes in Children: A Review Article

How to Cite This Article: Alavi S. Paraneoplastic Neurologic Syndromes in Children: A Review Article. Iran J Child Neurol. 2013Summer; 7(3): 6- 14.ObjectiveParaneoplastic neurological syndromes (PNS) were initially defined as neurological syndromes with unknown etiology that often associate with cancer. This broad definition may lead to misconception that any neurological syndrome, which coincides with a cancer might be considered as PNS. In the last two decades it has been suggested that PNSs are mainly immune-mediated. The detection of onconeural antibodies has been very helpful in indicating the existence of a tumor and defining a given neurological syndrome as paraneoplastic. However, PNS may occur without onconeural antibodies, and the antibodies can occur with no neurological syndrome; thus, their presence should not be the only condition to define a neurological syndrome as paraneoplastic. Diagnosis of paraneoplastic syndromes in children may result in early detection and treatment of the pediatric cancer and can reduce the neurological damage that is the major source of morbidity in children with successfully treated tumors. This study reviews the presenting symptoms, immunology, and management options for paraneoplastic syndromes, focusing on those most commonly reported in children.References1. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 200316; 349(16):1543-54.2. Siu LL, Chapman W, Moore MJ. Use of the somatostatinanalogue octreotide acetate in the treatment of encephalopathy associated with carcinoid tumor. Case report. Am J Clin Oncol 1997; 20(6): 558-61.3. Bataller L, Dalmau JO. Paraneoplastic disorders of the central nervous system: update on diagnostic criteria and treatment.Semin Neurol 2004 Dec; 24(4): 461-71.4. Graus F, Keime-Guibert F, Reñe R, Benyahia B, RibaltaT, Ascaso C, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001;124(Pt 6):1138-48.5. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis 2007 May 4; 2:22.6. Vianello M, Vitaliani R, Pezzani R, Nicolao P, Betterle C,Keir G, et al. The spectrum of antineuronal autoantibodies in a series of neurological patients. J Neurol Sci 2004;220(1-2):29-36.7. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75(8):1135-40.8. Scheid R, Honnorat J, Delmont E, Urbach H, Biniek R. A new anti-neuronal antibody in a case of paraneoplastic limbic encephalitis associated with breast cancer. J Neurol Neurosurg Psychiatry 2004;75(2):338-40.9. Altman AJ, Baehner RL. Favorable prognosis for survival in children with coincident opso-myoclonus and neuroblastoma. Cancer 1976;37:846-52.10. O’Neill JH, Murray NM, Newsom-Davis J. The Lambert- Eaton myasthenic syndrome. A review of 50 cases. Brain 1988;111(Pt 3):577-96.11. Bernal F, Shams’ili S, Rojas I, Sanchez-Valle R, Saiz A, et al. Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin’s disease. Neurology 2003;60(2):230-4.12. Croft PB, Urich H, Wilkinson M. Peripheral neuropathy of sensorimotor type associated with malignant disease. Brain 1967;90(1):31-66.13. Dalmau J, Rosenfeld MR: Paraneoplastic syndromes ofthe CNS. Lancet Neurol 2008;7(4):327-40.14. Albert ML, Austin LM, Darnell RB. Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration. Ann Neurol 2000;47(1):9-17.15. Okano HJ, Park WY, Corradi JP, Darnell RB. The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival. Genes Dev 1999;13(16):2087-97.16. Furneaux HM, Reich L, Posner JB. Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 1990;40(7):1085-91.17. Darnell RB. Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci U S A 1996; 93(10):4529-3618. Albert ML, Jegathesan M, Darnell RB. Dendritic cell maturation is required for the cross-tolerization of CD8+T cells. Nat Immunol 2001; 2(11):1010-7.19. Posner JB. Paraneoplastic opsoclonus/myoclonus: B cells, T cells, both, or neither? Neurology 2004; 62(9):1466–7.20. Jan H. de Graaf, Rienk Y. J. Tamminga, Willem A. Kamps. Paraneoplastic manifestations in children. Eur J Pediatr 1994;153(11):784-91.21. Turkel SB, Brumm VL, Mitchell WG, Tavare CJ. Mood and behavioral dysfunction with opsoclonus-myoclonus ataxia. J Neuropsychiatry Clin Neurosci 2006;18(2): 239-41.22. Brissaud HE, Beauvais P. Opsoclonus and neuroblastoma.N Engl J Med 1969; 280:1242.23. Harel S, Yurgenson U, Rechavi G, Burstein Y, Spirer Z.  Cerebellar ataxia and opsoclonus as the initial manifestations of myoclonic encephalopathy associated with neuroblastoma. Child Nerv Syst 1987; 3(4):245-247.24. Connolly AM, Pestronk A, Mehta S, Pranzatelli MR 3rd, Noetzel MJ. Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: an analysis of antigenic targets in neural tissues. J Pediatr 1997; 130(6): 878 -884.25. Blaes F, Pike MG, Lang B. Autoantibodies in childhood opsoclonus-myoclonus syndrome. J Neuroimmunol 2008; 201–202: 221-6. Epub 2008 Aug 6.26. Kirsten A, Beck S, Fühlhuber V, Kaps M, Kreutz T, Korfei M, et al: New autoantibodies in pediatric opsoclonus myoclonus syndrome. Ann N Y Acad Sci 2007; 1110:256-60.27. Sabater L, Xifró X, Saiz A, Alberch J, Graus F. Analysis of antibodies to neuronal surface antigens in adult opsoclonus-myoclonus. J Neuroimmunol 2008; 196(1-2):188–91.28. Pohl KR, Pritchard J, Wilson J. Neurological sequelae of thedancing eye syndrome. Eur J Pediatr 1996;155(3):237-44.29. Younes-Mhenni S, Janier MF, Cinotti L, Antoine JC, Tronc F, Cottin V, et al. FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes. Brain 2004 Oct;127 (Pt 10):2331–8. Epub 2004 Sep 10.30. Titulaer MJ, Soffietti R, Dalmau J, Gilhus NE, GiomettoB, Graus F, et al. Screening for tumours in paraneoplasticsyndromes: report of an EFNS Task Force. Eur J Neurol 2010; 18(1):19-e3. Epub 2010 Sep 29.31. Wells EM, Dalmau J. Paraneoplastic neurologic disorders in children. Curr Neurol Neurosci Rep 2011;11(2):187-94.32. Haberlandt E, Bast T, Ebner A, Holthausen H, Kluger G,Kravljanac R, et al. Limbic encephalitis in children and adolescents. Arch Dis Child. 2010; 96(2):186-91.33. Yeung WL, Li CK, Nelson EA, Chik KW, Joynt GM, Yuen E, et al. Unusual neurological presentation of neuroblastoma. Hong Kong Med J 2003; 9(2):142–4.34. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis:neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123 (Pt 7):1481-94.35. Vedeler CA, Antoine JC, Giometto B, Graus F, Grisold W, Hart IK, et al. Paraneoplastic Neurological Syndrome Euronetwork. Management of paraneoplastic neurological syndromes: report of an EFNS Task Force. Eur J Neurol. 2006 Jul; 13(7): 682-90.36. Darnell RB: NMDA receptor as a target in paraneoplasticencephalitis. Ann Neurol 2007; 61(1): 3-4.37. Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, et al. Paraneoplastic anti-Nmethyl-Daspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61(1): 25-36.38. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti- NMDA receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7(12):1091-98.39. Florance NR, Davis RL, Lam C, Szperka C, Zhou L,Ahmad S, et al. Anti-N-methyl-Daspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66(1):11-8. 40. Drukker CA, Heij HA, Wijnaendts LC, Verbeke JI, Kaspers GJ. Paraneoplastic gastro-intestinal anti-Hu syndrome in neuroblastoma. Pediatr Blood Cancer 2009; 52(3):396-8.41. Emir S, Kutluk MT, Göğüş S, Büyükpamukçu M.Paraneoplastic cerebellar degeneration and Horner syndrome: association of two uncommon findings in a child with Hodgkin disease. J Pediatr Hematol Oncol 2000; 22(2):158–61.42. de Buys Roessingh AS, Loriot MH, Wiesenauer C, LallierM. Lambert-Eaton myasthenic syndrome revealing an abdominal neuroblastoma. Pediatr Surg 2009; 44(8):E5–7.43. Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu associated paraneoplastic encephalomyelitis/sensory neuropathy: a clinical study of 71 patients. Medicine(Baltimore) 1992; 71(2):59–72.44. Ertle F, Behnisch W, Al Mulla NA, Bessisso M, RatingD, Mechtersheimer G, et al. Treatment of neuroblastoma- related opsoclonus - myoclonus-ataxia syndrome with high-dose dexamethasone pulses. Pediatr Blood Cancer 2008; 50(3):683–7.45. Pranzatelli MR, Tate ED, Swan JA, Travelstead AL, Colliver JA, Verhulst SJ, et al. B cell depletion therapy for new-onset opsoclonus-myoclonus. Mov Disord. 2010; 25(2): 238-42.46. Shams’ili S, de Beukelaar J, Gratama JW, Hooijkaas H, van den Bent M, van ‘t Veer M, et al. An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes. J Neurol 2006; 253(1):16-20.47. Alavi S, Kord Valeshabad A, Moradveisi B, Aminasnafi A, Arzanian MT. Clinical responses to rituximab in a case of neuroblastoma with refractory opsoclonus myoclonus ataxia syndrome. Case Rep Oncol Med 2012;2012:164082.48. Alavi S, Fahimzad A, Jadali F, Ghazizadeh F, RashidiA. Concurrent adrenal neuroblastoma and kawasaki disease: a report of a rare case.Case Rep Pediatr 2013;2013:931703.

The Micro-Shear bond strength of different cements to commercially pure titanium

The most appropriate luting agent for attaching the prefabricated Ti-based insert of hybrid abutments to its ceramic component has not yet been determined. This study was done aimed at examining the micro-shear bond strength (?SBS) of different cements to commercially pure titanium (Cp Ti). A total of 100 milled cubes of Cp Ti was airborne-particle abraded using 250 ?m aluminum oxide particles. Specimens were then divided into 5 groups (n=20) according to the type of resin cement used: (1) Panavia F.2, (2) Rely X U200, (3) Panavia SA LUTING Plus, (4) GC Fuji I, and (5) GC FujiCEM 2. After 24h storage, half of the samples were subjected to 5000 cycles of thermal aging. Next, the bonded samples were tested in the micro-shear mode. Data (MPa) were analyzed using a two-way ANOVA and the post hoc Tukey test (?=0.05). After debonding, each sample was examined for the failure mode classification. The highest ?SBS value in the study cements was obtained for Panavia F.2 cement (P<0.001) with no significant difference with Rely X U200 (P=0.07). The ?SBS values of both GI-based cements were significantly lower than those of resin cements. Thermal aging decreased the ?SBS values of all groups (P=0.003) significantly. The mainly occurred failure mode in all groups was the adhesive feature. Resin cements demonstrated acceptable bonding to Cp Ti, yet Gl-based cements did not. From among the cements examined, Panavia F.2 can be considered as the best option for bonding to Ti

Hemophagocytic Lymphohistiocytosis Complicating Erythroleukemia in a Child with Monosomy 7: A Case Report and Review of the Literature

Herein, the first case of childhood erythrophagocytosis following chemotherapy for erythroleukemia in a child with monosomy 7 is reported. A 5-year-old boy presented with anemia, thrombocytopenia, and hepatosplenomegaly in whom erythroleukemia was diagnosed. Prolonged pancytopenia accompanied by persistent fever and huge splenomegaly and hepatomegaly became evident after 2 courses of chemotherapy. On bone marrow aspiration, macrophages phagocytosing erythroid precursors were observed and the diagnosis of HLH was established; additionally, monosomy 7 was detected on bone marrow cytogenetic examination. In conclusion, monosomy 7 can lead to erythrophagocytosis associated with erythroid leukemia and should be considered among the chromosomal abnormalities contributing to the association

Multifocal kaposiform hemangioendothelioma of soft tissue with bilateral pulmonary involvement in an adolescent

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor of intermediate malignancy with resemblance to Kaposi sarcoma. It occurs predominantly in pediatric age groups as a cutaneous lesion with focal infiltration into the adjacent soft tissue and bone. Although visceral involvement is very uncommon, several cases with bone, retroperitoneal, or mediastinal involvement have been described. KHE has been reported to occasionally occur in unusual sites such as the thymus, tonsils, larynx, paranasal sinuses, deltoid muscle, spleen, uterine cervix, thoracic spine, and even the breast. Multifocal KHE is an extremely rare entity with few reports available in the literature, none of which describes pulmonary involvement. Herein, we report a unique case of multifocal KHE in a 13-year-old boy presenting with a huge soft tissue mass in the upper extremity complicated by bilateral pulmonary nodules that developed into large, necrotic tumor masses

Retroperitoneal Malignant Peripheral Nerve Sheath Tumor Replacing an Absent Kidney in a Child

Malignant peripheral nerve sheath tumors (MPNSTs) are nonrhabdomyosarcoma soft tissue sarcomas with rare occurrence in children specially in the retroperitoneum. We describe a young child who presented with an abdominal mass. Both ultrasound and computed tomography revealed a large right-sided abdominal mass in the anatomic place of right kidney, while no kidney or ureter was observed at that side. He underwent surgical resection of the tumor with a primary impression of Wilms tumor. To the authors’ knowledge, this is the first case of retroperitoneal malignant peripheral nerve sheath tumor and absent kidney. This case suggests the very rare probability of association of MPNSTs in children with genitourinary tract anomalies such as renal agenesis

Autoimmune Lymphoproliferative Syndrome; A Case Report

Autoimmune lymphoproliferative syndrome is a disorder of lymphoid system regulation characterized by chronic splenomegaly, lymphadenopathy and autoimmune phenomena especially immune-mediated cytopenias. The hallmark of the disease is the presence in peripheral blood and lymphoid tissue of increased numbers of a normally rare T lymphocyte subset, usually referred to as “double-negative” T cells. Here the authors report a 16-year-old boy when he was first hospitalized for diffuse petechiae, purpura and epistaxis at 9 years of age.One year later,he was readmitted for high fever and recurring cytopenia. On examination several enlarged, nontender lymph nodes involving cervical and submandibular areas and a huge spleen were detected.Lymph node biopsy was performed two times. According to flowcytometry of peripheral blood and immunophenotyping of lymph node tissues which revealed increased numbers of CD3+CD4-CD8-T lymphocytes, autoimmune lymphoproliferative syndrome was suggested for him. Autoimmune lymphoproliferative syndrome should be considered in differential diagnosis of any patient with unexplained Coomb’s positive cytopenias, hypergammaglobulinemia, generalized lymphadenopathy and splenomegaly. The confirmation of the diagnosis should be based upon genetic analysis and detection of the affected genes involved in fas pathway