Letter to the Editor
Immunosuppressive therapy in opsoclonus-myoclonus-ataxia syndrome associated with paravertebral neuroblastoma
Terapia inmunosupresora en síndrome de opsoclonus-mioclonus ataxia asociado a un neuroblastoma paravertebral
A. Castañón-Gonzáleza, E. Barragán-Pérezb, G. Hernández-Pliegoc, J.C. López-Valdésd,e,
Corresponding author
a Departamento de Neurología, Unidad Médica de Alta Especialidad, Hospital de Pediatría “Dr. Silvestre FrenkFreund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (I.M.S.S.), Ciudad de México, Mexico
b Departamento de Neurología, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico
c Departamento de Oncología, Unidad de Hemato-oncología, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico
d Departamento de investigación, Facultad de Medicina de Tampico “Dr. Alberto RomoCaballero”, Universidad Autónoma de Tamaulipas, Tampico, Tamaulipas, Mexico
e CognitiveScience, S.A., Ciudad de México, Mexico
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Castañón-González, E. Barragán-Pérez, G. Hernández-Pliego, J.C. López-Valdés" "autores" => array:4 [ 0 => array:3 [ "nombre" => "A." "apellidos" => "Castañón-González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Barragán-Pérez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "G." "apellidos" => "Hernández-Pliego" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:4 [ "nombre" => "J.C." "apellidos" => "López-Valdés" "email" => array:1 [ 0 => "jc.lopz@live.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Departamento de Neurología, Unidad Médica de Alta Especialidad, Hospital de Pediatría “Dr. Silvestre FrenkFreund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (I.M.S.S.), Ciudad de México, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Neurología, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Oncología, Unidad de Hemato-oncología, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de investigación, Facultad de Medicina de Tampico “Dr. Alberto RomoCaballero”, Universidad Autónoma de Tamaulipas, Tampico, Tamaulipas, Mexico" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "CognitiveScience, S.A., Ciudad de México, Mexico" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Terapia inmunosupresora en síndrome de <span class="elsevierStyleItalic">opsoclonus-mioclonus</span> ataxia asociado a un neuroblastoma paravertebral" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1765 "Ancho" => 2133 "Tamanyo" => 238111 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Axial CT image revealing a paravertebral mass at the level of T7, with no signs of invasion of peripheral tissues. (B) <span class="elsevierStyleSup">131</span>I-MIBG SPECT image showing an area positive for chromaffin tissue. (C and D) Coronal and parasagittal sections revealing a space-occupying mass in the paravertebral region between T6 and T10.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Kinsbourne syndrome, or opsoclonus-myoclonus-ataxia syndrome (OMAS), is a rare aggressive, recurrent, chronic neurological disease of paraneoplastic, parainfectious, or idiopathic origin that also involves the immune system. It negatively affects a critical stage in neurodevelopment as it most frequently appears in paediatric patients aged 6 months to 3 years. The syndrome is characterised by acute or subacute opsoclonus (large, rapid, multi-directional saccades), truncal instability, cerebellar ataxia, and diffuse myoclonus.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1–3</span></a> In addition to these classic manifestations, the condition may also be associated with irritability, alterations in the sleep-wake cycle, headache, language or visual disorders, dysphagia, vomiting, sialorrhoea, and lethargy.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As most cases are associated with infections, immunisations, and immunological alterations, there is now extensive evidence that the syndrome is of immune origin, and may be mediated by antibodies associated with dysfunction of T- and B-cells or by antibodies against ACTH, neurofilament proteins, Hu (ANNA-1), Ri (ANNA-2), Yo, Tr, glutamic acid decarboxylase, or amphiphysin. However, the specific antibody responsible for the syndrome is yet to be identified, hence the current lack of treatment models based on the results of clinical trials of systematic treatment protocols. Current treatment for Kinsbourne syndrome includes high-dose corticosteroids, ACTH, intravenous immunoglobulins, cyclophosphamide, plasmapheresis, and even rituximab.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1–4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of a patient who received immunosuppressant therapy with dexamethasone, intravenous human immunoglobulin (IVIg), cyclophosphamide, and verapamil.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Our patient was a previously healthy 9-month-old infant from the State of Mexico. She had last been vaccinated at 6 months of age. She was admitted due to a 3-week history of fourth cranial nerve palsy, truncal ataxia, and irritability. Ataxia worsened 2 weeks after the onset of the initial symptoms, with the patient becoming unable to sit and progressively developing opsoclonus and sleep-wake cycle alterations. Head CT (1 January 2015) and brain MRI scans (2 January 2015) ruled out space-occupying, inflammatory, and demyelinating lesions. Suspecting postinfectious cerebellitis, we performed a lumbar puncture, with negative results for CSF cytochemical and cytological analyses, Gram staining, CSF cultures, and viral serology tests. As OMAS was suspected, we performed chest CT and <span class="elsevierStyleSup">131</span>I-MIBG SPECT scans (30 January 2015), detecting a tumour in the right paravertebral region (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The mass was surgically removed; anatomical pathology findings indicated differentiating neuroblastoma. We confirmed diagnosis of OMAS of paraneoplastic aetiology and started treatment with monthly cycles of dexamethasone (dosed at 20<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> for 3 days), IVIg (2<span class="elsevierStyleHsp" style=""></span>g/kg), and cyclophosphamide (150<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> for 7 days), in addition to verapamil (15<span class="elsevierStyleHsp" style=""></span>mg/8<span class="elsevierStyleHsp" style=""></span>h, until adolescence), for 6 months. After 2 years of treatment, the patient is in complete remission and has no sequelae.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Multiple treatment protocols for OMAS have been developed. When the syndrome is of paraneoplastic origin, the most frequent treatment approach constitutes surgical resection of the tumour followed by immunomodulatory therapy with ACTH and IVIg.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> Due to the aggressiveness of the syndrome, however, treatment aims to reduce the formation of antibodies potentially involved in the pathophysiology of the condition,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> which leads to symptom resolution. In our case, we decided to administer corticosteroids and immunoglobulin to reduce lymphocytic and phagocytic responses and the production of interleukins.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> Combining these 2 drugs has the advantage of inducing immunomodulation without immunosuppression, leading to complete resolution of neurological symptoms in cases of paraneoplastic OMAS.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> Cyclophosphamide, on the other hand, is an alkylating agent and immunosuppressant used in the treatment of autoimmune disorders.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1,6</span></a> In recent years, various studies have shown that long-term treatment with P-glycoprotein inhibitors (eg, verapamil) reduces IL-2 production and T-cell proliferation in vitro.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Although delays in diagnosis or initiation of immunotherapy may result in brain injury, with irreversible neurological impairment, verapamil is reported to protect against cognitive and behavioural disorders in experimental models of Alzheimer disease, as it blocks calcium entry into neurons, inhibits lipopolysaccharide-induced dopaminergic neurotoxicity, and decreases the production of inflammatory mediators from microglial NADPH oxidase<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a>; this was the reason for our decision to add the drug to our patient's regime.</p><p id="par0035" class="elsevierStylePara elsevierViewall">OMAS in paediatric patients is associated with poor prognosis, with fewer than 20% of cases showing complete recovery. It usually becomes chronic, with relapses varying in number and intensity.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> Our patient, however, remained asymptomatic and displayed no short-term sequelae after 24 months of treatment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Future studies with longer follow-up periods and larger samples should aim to determine whether the treatment administered to our patient is as effective as or more effective than ACTH for OMAS. In any case, treatment should be multidisciplinary and tailored to each patient's needs.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Castañón-González A, Barragán-Pérez E, Hernández-Pliego G, López-Valdés JC. Terapia inmunosupresora en síndrome de <span class="elsevierStyleItalic">opsoclonus-mioclonus</span> ataxia asociado a un neuroblastoma paravertebral. Neurología. 2020;35:54–56.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1765 "Ancho" => 2133 "Tamanyo" => 238111 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Axial CT image revealing a paravertebral mass at the level of T7, with no signs of invasion of peripheral tissues. (B) <span class="elsevierStyleSup">131</span>I-MIBG SPECT image showing an area positive for chromaffin tissue. (C and D) Coronal and parasagittal sections revealing a space-occupying mass in the paravertebral region between T6 and T10.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Kinsbourne syndrome: case report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.V.M. Maranhão" 1 => "A.C.F. de Holanda" 2 => "F.L. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 0 | 3 |
| 2024 October | 54 | 12 | 66 |
| 2024 September | 78 | 17 | 95 |
| 2024 August | 53 | 5 | 58 |
| 2024 July | 53 | 8 | 61 |
| 2024 June | 58 | 10 | 68 |
| 2024 May | 59 | 5 | 64 |
| 2024 April | 47 | 50 | 97 |
| 2024 March | 86 | 5 | 91 |
| 2024 February | 95 | 11 | 106 |
| 2024 January | 73 | 8 | 81 |
| 2023 December | 76 | 14 | 90 |
| 2023 November | 87 | 12 | 99 |
| 2023 October | 84 | 14 | 98 |
| 2023 September | 67 | 9 | 76 |
| 2023 August | 56 | 6 | 62 |
| 2023 July | 61 | 10 | 71 |
| 2023 June | 74 | 1 | 75 |
| 2023 May | 107 | 8 | 115 |
| 2023 April | 98 | 8 | 106 |
| 2023 March | 51 | 4 | 55 |
| 2023 February | 53 | 4 | 57 |
| 2023 January | 54 | 5 | 59 |
| 2022 December | 52 | 11 | 63 |
| 2022 November | 55 | 20 | 75 |
| 2022 October | 51 | 5 | 56 |
| 2022 September | 65 | 16 | 81 |
| 2022 August | 67 | 11 | 78 |
| 2022 July | 37 | 11 | 48 |
| 2022 June | 65 | 9 | 74 |
| 2022 May | 72 | 16 | 88 |
| 2022 April | 63 | 5 | 68 |
| 2022 March | 94 | 16 | 110 |
| 2022 February | 57 | 14 | 71 |
| 2022 January | 79 | 7 | 86 |
| 2021 December | 37 | 12 | 49 |
| 2021 November | 26 | 7 | 33 |
| 2021 October | 49 | 10 | 59 |
| 2021 September | 60 | 18 | 78 |
| 2021 August | 61 | 9 | 70 |
| 2021 July | 55 | 8 | 63 |
| 2021 June | 49 | 15 | 64 |
| 2021 May | 78 | 12 | 90 |
| 2021 April | 151 | 17 | 168 |
| 2021 March | 85 | 9 | 94 |
| 2021 February | 77 | 14 | 91 |
| 2021 January | 67 | 27 | 94 |
| 2020 December | 59 | 9 | 68 |
| 2020 November | 46 | 8 | 54 |
| 2020 October | 32 | 10 | 42 |
| 2020 September | 75 | 20 | 95 |
| 2020 August | 35 | 10 | 45 |
| 2020 July | 26 | 12 | 38 |
| 2020 June | 33 | 23 | 56 |
| 2020 May | 5 | 10 | 15 |
| 2020 April | 11 | 8 | 19 |
| 2020 March | 0 | 5 | 5 |
| 2020 February | 0 | 11 | 11 |
| 2020 January | 0 | 12 | 12 |
| 2019 December | 0 | 5 | 5 |
| 2019 November | 0 | 8 | 8 |
| 2019 October | 0 | 10 | 10 |
| 2019 September | 0 | 6 | 6 |
| 2019 August | 0 | 2 | 2 |
| 2019 July | 0 | 5 | 5 |
| 2019 June | 0 | 14 | 14 |
| 2019 May | 0 | 0 | 0 |
| 2019 April | 0 | 12 | 12 |
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