Letter to the Editor
Multiple cranial neuropathy secondary to neurolymphomatosis as initial presentation of lymphoma
Multineuritis craneal por neurolinfomatosis primaria como manifestación inicial de linfoma
A.M. Diezma-Martín
, M.I. Morales-Casado, M. de la Torre de la Paz, R. Almansa-Castillo
Corresponding author
Hospital Universitario de Toledo, Toledo, Spain
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Diezma-Martín, M.I. Morales-Casado, M. de la Torre de la Paz, R. Almansa-Castillo" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A.M." "apellidos" => "Diezma-Martín" "email" => array:2 [ 0 => "alba1794@gmail.com" 1 => "adiezma@sescam.jccm.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.I." "apellidos" => "Morales-Casado" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "de la Torre de la Paz" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Almansa-Castillo" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Universitario de Toledo, Toledo, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Multineuritis craneal por neurolinfomatosis primaria como manifestación inicial de linfoma" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 791 "Ancho" => 805 "Tamanyo" => 104479 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Abdomen axial CT scan with intravenous contrast. Both kidneys present hypodense, poorly defined, infiltrative masses mainly affecting the renal medulla.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Multiple cranial neuropathy refers to the involvement of multiple cranial nerves; its differential diagnosis is complex and includes several diseases.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">One possible aetiology of cranial neuropathy is neurolymphomatosis, which is defined as the infiltration of malignant lymphoid cells into peripheral, spinal, or cranial nerves or plexi, affecting several territories.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Ninety percent of cases are associated with non-Hodgkin lymphomas and 10% with leukaemia, with a poorly defined incidence rate. It may appear as the initial manifestation of the (primary) oncological process.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> Primary neurolymphomatosis is a rare disease, with little information available on its form of presentation, course, diagnosis, and treatment, hence the interest of the present report.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of a 36-year-old man with no relevant medical history. Over the course of 3 months, he progressively developed symptoms of paralysis of the left abducens nerve, left peripheral facial palsy, which subsequently improved, and right peripheral facial palsy. At admission, the neurological examination revealed cranial nerve involvement (both abducens nerves and right facial nerve), with no other relevant finding. We observed no alterations in the initial assessment, which included neuroimaging studies (brain CT, contrast-enhanced MRI study of the brain and base of the skull), blood analysis (biochemistry, microbiological study, tumour markers, autoimmune study, angiotensin-converting enzyme [ACE], vitamin B<span class="elsevierStyleInf">12</span>, folic acid, thyroid hormones, total protein test, electrophoresis, serology tests, and rapid antigen test and polymerase chain reaction test for SARS-CoV-2), and testicular and thyroid ultrasound.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The cerebrospinal fluid (CSF) analysis after lumbar puncture showed lymphocytic pleocytosis (68<span class="elsevierStyleHsp" style=""></span>cells/mm<span class="elsevierStyleSup">3</span>, glucose level of 51<span class="elsevierStyleHsp" style=""></span>mg/dL, and total protein level of 38.00<span class="elsevierStyleHsp" style=""></span>mg/dL) but the remaining findings (cytobiochemistry, ACE, oligoclonal bands, microbiology study, Gram staining, cultures, and serology studies) were negative.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Most CSF lymphocytes presented atypical morphological characteristics under the light microscope, and a flow cytometry study showed an abnormal lymphocyte population expressing an immunophenotype compatible with leukaemia/T-lymphoblastic lymphoma.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Considering these findings, we requested a chest, abdomen, and pelvis CT scan, which revealed an infiltrative renal mass (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). A thick-needle biopsy and anatomical pathology study of a sample from the right renal mass confirmed infiltration of the renal parenchyma by an atypical lymphoid population with a high proliferative index, compatible with T-lymphoblastic lymphoma. Bone marrow biopsy showed mild infiltration (1.6%). The patient started treatment with dexamethasone at 6<span class="elsevierStyleHsp" style=""></span>mg every 6 hours.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">After the definitive diagnosis of T-lymphoblastic lymphoma, he started triple intrathecal therapy (TIT; methotrexate, cytarabine, and hydrocortisone) and intensive systemic chemotherapy following the 2011 protocol for acute lymphoblastic lymphoma.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The patient responded well to treatment, with progressive improvement and eventually resolution of neurological symptoms. After one TIT cycle, CSF was acellular and flow cytometry revealed no disease. A follow-up CT scan showed almost complete resolution of the renal masses. The patient was transferred to the haematology department with no neurological symptoms.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Multiple cranial neuropathy requires good clinical integration and comprehensive assessment, with a broad differential diagnosis including multiple aetiologies (neoplastic, infectious, vascular, autoimmune).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> These symptoms may develop as a result of involvement at any anatomical location, from the brainstem to the peripheral nerves. Once the aetiology of the symptoms has been identified, the therapeutic approach to multiple cranial neuropathy consists of specifically treating the underlying condition.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">One of the least frequent aetiologies causing these symptoms is neurolymphomatosis. Neurolymphomatosis may precede the systemic disease in up to 25% of cases.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> As this manifestation is rare in malignant haematological disorders, its diagnosis is sometimes delayed and its incidence remains unknown.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The clinical heterogeneity and non-specific brain imaging findings, together with the low yield of CSF analysis (lymphoma cells are detected in only 20%–40% of cases) may lead to underdiagnosis and delayed treatment of the underlying haematological disorder. Early treatment of the underlying condition leads to better prognosis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">To date, there is no consensus on the optimal treatment; the literature mentions intensive chemotherapy with regimes intended to treat primary CNS lymphoma or relapsed lymphoma.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> In the case of neurolymphomatosis in T-lymphoblastic lymphoma,<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,11</span></a> therapeutic strategies are the same as those used in acute lymphoblastic leukaemia.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> Treatment should be based on consensus between experienced haematologists.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Regarding prognosis, the majority of patients respond well to initial chemotherapy, achieving good functional outcomes. However, long-term prognosis is poor, with a mean survival time of 10 months, which may be somewhat longer in the case of primary lymphomatosis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">This study received no funding of any kind.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 791 "Ancho" => 805 "Tamanyo" => 104479 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Abdomen axial CT scan with intravenous contrast. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 0 | 4 |
| 2024 October | 32 | 4 | 36 |
| 2024 September | 45 | 15 | 60 |
| 2024 August | 48 | 18 | 66 |
| 2024 July | 48 | 10 | 58 |
| 2024 June | 47 | 3 | 50 |
| 2024 May | 43 | 5 | 48 |
| 2024 April | 36 | 16 | 52 |
| 2024 March | 37 | 3 | 40 |
| 2024 February | 41 | 17 | 58 |
| 2024 January | 39 | 8 | 47 |
| 2023 December | 52 | 8 | 60 |
| 2023 November | 48 | 26 | 74 |
| 2023 October | 39 | 14 | 53 |
| 2023 September | 28 | 1 | 29 |
| 2023 August | 24 | 6 | 30 |
| 2023 July | 17 | 6 | 23 |
| 2023 June | 42 | 5 | 47 |
| 2023 May | 54 | 2 | 56 |
| 2023 April | 28 | 5 | 33 |
| 2023 March | 12 | 5 | 17 |
| 2023 February | 24 | 4 | 28 |
| 2023 January | 16 | 14 | 30 |
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