Letter to the Editor
Atypical paraneoplastic syndrome with no onconeuronal antibodies: A case report
Síndrome paraneoplásico atípico sin anticuerpos onconeuronales detectables: a propósito de un caso
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Casas Peña, M.A. Martín Santidrián, J. González Fernández, M.V. Castrillo Fraile" "autores" => array:4 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Casas Peña" "email" => array:1 [ 0 => "elena.caspe@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.A." "apellidos" => "Martín Santidrián" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "González Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M.V." "apellidos" => "Castrillo Fraile" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario de Burgos, Burgos, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Rehabilitación, Hospital Universitario de Burgos, Burgos, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome paraneoplásico atípico sin anticuerpos onconeuronales detectables: a propósito de un caso" ] ] "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" => 1096 "Ancho" => 1800 "Tamanyo" => 87137 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Brain MRI. T2-weighted FLAIR sequence. A) Baseline: bilateral diffuse involvement of the white matter, except for the U-shaped fibres. B) Three months after tumour resection: decreased leukoencephalopathy (barely visible).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Paraneoplastic neurological syndromes (PNS) constitute a heterogeneous group of immunopathogenic disorders caused by tumours located outside the nervous system. Before the diagnosis is established, we must rule out neurological complications resulting directly from the tumour or its treatment.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> From a pathophysiological perspective, PNS are explained by the presence of common antigens in tumour cells and in some structures of the nervous system, with the result that the antitumour immune response also affects healthy cells.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,3</span></a> According to the PNS diagnostic criteria, detection of both the onconeuronal antibodies and the primary tumour are 2 of the most useful factors when establishing diagnosis. However, not all patients present circulating antibodies<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a>: these may go undetected in up to 50% of patients,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> as in our case.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our patient is a 68-year-old woman who presented progressive dyspnoea associated with pulmonary thromboembolism and deep vein thrombosis, as well as confusional syndrome and secondarily generalised partial seizures. After a 2-month improvement period, she once again presented confusional syndrome, gait ataxia, and recurrent seizures leading to status epilepticus.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The blood analysis displayed normal results (including thyroid and parathyroid hormone levels, vitamins, folic acid, CEA, and Ca 15.3); results for angiotensin-converting enzyme, long-chain fatty acids, serum and urine protein test, and immunofixation were also normal. The autoimmunity study (anti-DNA antibodies, IgM and IgG anti-cardiolipin antibodies, anti-Cenp-B antibodies, anti-histone antibodies, anti-Jo-1/HRS antibodies, anti-nucleosome antibodies, anti-PCNA antibodies, anti-PM/Scl antibodies, anti-ribosomal P antibodies, anti-topo I (Scl-70) antibodies, anti-Sm antibodies, anti-RNP/Sm antibodies, anti-SSA/Ro60 antibodies, anti-SS-A/Ro52 antibodies, anti-SS-B/La antibodies, antimicrosomal antibodies, TSH receptor antibodies, anti-thyroglobulin antibodies) yielded normal results, with the exception of those for anti-nuclear antibodies. Serology tests for syphilis, HIV, and JC virus returned negative results. The CSF analysis only revealed high protein levels (118<span class="elsevierStyleHsp" style=""></span>mg/dL), with negative results for Gram staining, cultures, and cytology study. No intracellular onconeural antibodies or surface antigen antibodies were detected in the serum or the CSF (anti-Hu, Yo, Ri, CV2, PNMA 2 [Ma2/Ta], amphiphysin, recoverin, Sox1, titin, Zic 4, GAD65, and Tr [DNCR]).</p><p id="par0020" class="elsevierStylePara elsevierViewall">A brain MRI scan revealed bilateral supratentorial leukoencephalopathy, with no gadolinium contrast enhancement or specific findings (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Several electroencephalography (EEG) studies revealed diffuse slowing with occasional epileptiform activity. An electromyography study revealed an asymmetrical demyelinating/axonal sensorimotor polyneuropathy of distal predominance, which was more pronounced in the lower limbs.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">We ruled out thiamine deficiency, toxic-metabolic, inflammatory, and infectious encephalopathy. Given suspicion of atypical PNS, complementary tests were performed, revealing an invasive ductal carcinoma in the left breast (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), with no signs of metastasis. After surgical resection of the tumour and hormone therapy with exemestane and radiation therapy, the patient progressed favourably, showing normal results in a neurological examination and EEG study at 3 months. A brain MRI scan revealed that leukoencephalopathy had significantly decreased and was barely visible (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Having ruled out other causes and in the absence of a better explanation, we diagnosed the patient with atypical PNS (acute encephalopathy, secondarily generalised partial seizures, and asymmetric demyelinating/axonal sensorimotor polyneuropathy). The favourable clinical outcome and the normal MRI, EEG, and CSF findings after tumour treatment (without immunosuppressants) suggests that a coincidental association is unlikely and points to a definitive diagnosis of PNS.</p><p id="par0035" class="elsevierStylePara elsevierViewall">We stress the importance of maintaining a high level of suspicion of PNS (a potentially curable disease) in cases of neurological alterations of unknown cause, once other conditions have been ruled out, even in the absence of onconeuronal antibodies, since this does not rule out the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Although cases of PNS with no known associated autoantibodies have been described, cases with such complex clinical symptoms are rare. The clinical heterogeneity of our case represents a contribution to the existing knowledge on atypical PNS. Furthermore, it demonstrates the need for studies revealing improvement, which is mandatory in the absence of autoimmune markers.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Author contributions</span><p id="par0045" class="elsevierStylePara elsevierViewall">Study design, drafting, and approval of the final version: E. Casas Peña.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Approval of the final version: M.A. Martín Santidrián and J. González Fernández.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Drafting: M.V. Castrillo Fraile.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Author contributions" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Casas Peña E, Martín Santidrián MA, González Fernández J, Castrillo Fraile MV. Síndrome paraneoplásico atípico sin anticuerpos onconeuronales detectables: a propósito de un caso. Neurología. 2019;34:207–209.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1096 "Ancho" => 1800 "Tamanyo" => 87137 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Brain MRI. T2-weighted FLAIR sequence. A) Baseline: bilateral diffuse involvement of the white matter, except for the U-shaped fibres. B) Three months after tumour resection: decreased leukoencephalopathy (barely visible).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 595 "Ancho" => 900 "Tamanyo" => 33691 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Full-body CT scan. Nodular lesion with poorly-defined edges in the left thoracic wall, corresponding to breast cancer.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommended diagnostic criteria for paraneoplastic neurological syndromes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Graus" 1 => "J.Y. Delattre" 2 => "J.C. Antoine" 3 => "J. Dalmau" 4 => "B. Giometto" 5 => "W. 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Bertolini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Neurol" "fecha" => "2010" "volumen" => "67" "paginaInicial" => "330" "paginaFinal" => "335" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0055" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identificación y utilidad clínica de los anticuerpos antineuronales" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Carrasco" 1 => "I. Alarcon" 2 => "C. González" 3 => "F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 7 | 8 | 15 |
| 2024 September | 36 | 4 | 40 |
| 2024 August | 30 | 7 | 37 |
| 2024 July | 13 | 2 | 15 |
| 2024 June | 14 | 8 | 22 |
| 2024 May | 29 | 11 | 40 |
| 2024 April | 19 | 23 | 42 |
| 2024 March | 37 | 15 | 52 |
| 2024 February | 14 | 15 | 29 |
| 2024 January | 33 | 10 | 43 |
| 2023 December | 33 | 12 | 45 |
| 2023 November | 29 | 11 | 40 |
| 2023 October | 37 | 15 | 52 |
| 2023 September | 27 | 7 | 34 |
| 2023 August | 23 | 5 | 28 |
| 2023 July | 43 | 7 | 50 |
| 2023 June | 45 | 1 | 46 |
| 2023 May | 51 | 6 | 57 |
| 2023 April | 54 | 0 | 54 |
| 2023 March | 37 | 3 | 40 |
| 2023 February | 39 | 9 | 48 |
| 2023 January | 17 | 8 | 25 |
| 2022 December | 45 | 4 | 49 |
| 2022 November | 37 | 10 | 47 |
| 2022 October | 25 | 10 | 35 |
| 2022 September | 35 | 12 | 47 |
| 2022 August | 46 | 12 | 58 |
| 2022 July | 33 | 7 | 40 |
| 2022 June | 40 | 6 | 46 |
| 2022 May | 36 | 11 | 47 |
| 2022 April | 42 | 8 | 50 |
| 2022 March | 81 | 11 | 92 |
| 2022 February | 87 | 3 | 90 |
| 2022 January | 56 | 7 | 63 |
| 2021 December | 52 | 11 | 63 |
| 2021 November | 68 | 8 | 76 |
| 2021 October | 55 | 15 | 70 |
| 2021 September | 41 | 14 | 55 |
| 2021 August | 23 | 18 | 41 |
| 2021 July | 25 | 6 | 31 |
| 2021 June | 23 | 12 | 35 |
| 2021 May | 40 | 13 | 53 |
| 2021 April | 97 | 10 | 107 |
| 2021 March | 52 | 11 | 63 |
| 2021 February | 36 | 6 | 42 |
| 2021 January | 31 | 10 | 41 |
| 2020 December | 53 | 7 | 60 |
| 2020 November | 44 | 14 | 58 |
| 2020 October | 33 | 5 | 38 |
| 2020 September | 24 | 35 | 59 |
| 2020 August | 23 | 30 | 53 |
| 2020 July | 32 | 11 | 43 |
| 2020 June | 28 | 11 | 39 |
| 2020 May | 29 | 14 | 43 |
| 2020 April | 28 | 10 | 38 |
| 2020 March | 31 | 7 | 38 |
| 2020 February | 25 | 2 | 27 |
| 2020 January | 23 | 6 | 29 |
| 2019 December | 72 | 7 | 79 |
| 2019 November | 24 | 9 | 33 |
| 2019 October | 14 | 3 | 17 |
| 2019 September | 26 | 7 | 33 |
| 2019 August | 15 | 1 | 16 |
| 2019 July | 21 | 10 | 31 |
| 2019 June | 60 | 26 | 86 |
| 2019 May | 127 | 15 | 142 |
| 2019 April | 61 | 12 | 73 |
| 2019 March | 8 | 3 | 11 |
| 2019 February | 6 | 6 | 12 |
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