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      Multiple Cranial Neuropathies as the Presenting Sign in a Patient with Metastatic BRAF-Mutated Lung Adenocarcinoma with Leptomeningeal Involvement

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          Abstract

          Leptomeningeal carcinomatosis accounts for only 4% of cases of multiple cranial neuropathies. Here, we report the case of a patient who presented with multiple synchronous cranial neuropathies. After treatment for neuroborreliosis and broad infectious workup, endobronchial ultrasound-guided mediastinal lymph node biopsy confirmed a diagnosis of metastatic BRAF-mutated lung adenocarcinoma with leptomeningeal involvement. To our knowledge, this is the first reported case of metastatic BRAF-driven lung adenocarcinoma with leptomeningeal disease at diagnosis. In this case, the presence of leptomeningeal carcinomatosis at diagnosis, not as a late manifestation of heavily pretreated disease, alludes to a possible association between leptomeningeal involvement and BRAF-mutated non-small cell lung cancer.

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          Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients.

          R Wasserstrom, J Posner, Elizabeth Glass (1982)
          The clinical findings and response to treatment of leptomeningeal metastases from solid tumors are analyzed in 90 patients treated at Memorial Sloan-Kettering Cancer Center during the period from January 1975 to February 1980. Patients included those who had either typical clinical findings of leptomeningeal tumor or conclusive laboratory evidence supporting the diagnosis. Carcinoma of the breast (46 patients), lung (23 patients) and melanoma (11 patients) were the common primary tumors. Symptoms of leptomeningeal metastasis occurred as the presenting sign in five patients and as late as ten years after the primary tumor was diagnosed in four other patients. Most patients had active systemic disease outside the nervous system. Signs and symptoms could be classified as involving either the brain, cranial nerves, or spinal nerves. Most patients had either symptoms or signs in more than one area at the time the diagnosis was established. The initial spinal fluid examination was abnormal in all but three patients, but only 49 had cytologic evidence of leptomeningeal metastases. Repeated spinal fluid assay yielded a positive cytology in 82 patients. Measurement of biochemical markers, including beta-glucuronidase, carcinoembryonic antigen and lactic dehydrogenase, assisted in the diagnosis. Approximately half of the patients treated by intraventricular methotrexate experienced improvement or stabilization of neurological symptoms for more than a month; median survival was 5.8 months after diagnosis, with a range of 1--29 months. In 18 patients disease was limited to the nervous system, and median survival was eight months, with four patients surviving one year and two patients for two years. Side effects of therapy were, for the most part, minor. We conclude that vigorous treatment of leptomeningeal metastases with intrathecal chemotherapeutic agents improves symptomatology in some patients, and at times prolongs survival.
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            Multiple cranial nerve palsies: analysis of 979 cases.

            Christopher R Keane (2005)
            To my knowledge, no large series of multiple cranial neuropathies is available. To examine the seats and causes of multiple cranial neuropathies in a large group of inpatients. Personal case series. Wards of a large municipal hospital and affiliated rehabilitation hospital. A consecutive series of 979 unselected inpatients with simultaneous or serial involvement of 2 or more different cranial nerves. Cranial nerves VI (565 cases), VII (466 cases), V (353 cases), and III (339 cases) were most commonly affected. The locations and causes were diverse, with cavernous sinus (252 cases), brainstem (217 cases), and individual nerves (182 cases) being the most frequent sites, and tumor (305 cases), vascular disease (128 cases), trauma (128 cases), infection (102 cases), and the Guillain-Barré and Fisher syndromes (91 cases total) being the most frequent causes. Recurrent cranial neuropathy was uncommon (43 cases, 106 episodes, 136 nerves), with diabetes mellitus (14 cases), self-limited unknown causes (14 cases), and idiopathic cavernous sinusitis (10 cases) being the usual causes. While the locations and causes of multiple cranial neuropathy are highly diverse, the fact that tumor composes more than one quarter of cases places a premium on prompt diagnosis.
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              Risk factors for brain metastases in patients with non–small‐cell lung cancer

              Ning An, Wang Jing, Haoyi Wang … (2018)
              Abstract Brain metastases (BM) are severe incidents in patients with non–small‐cell lung cancer (NSCLC). The controversial value of prophylactic cranial irradiation (PCI) in NSCLC in terms of survival benefit prompted us to explore the possible risk factors for BM in NSCLC and identify the potential population most likely to benefit from PCI. Risk factors for brain metastases in NSCLC are reviewed in this article. Identifying patients with a higher risk of BM could possibly increase the benefit of PCI while reducing the discomfort and risks caused by unnecessary invasive procedures in the NSCLC patient population. Future studies might focus on finding a solid basis for the prediction of the occurrence of brain metastases and for the therapeutic decision on the use of PCI.
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                Author and article information

                Journal
                Journal ID (publisher-id): CRO
                Journal ID (pmc): CRO
                Journal ID (doi): 10.1159/issn.1662-6575
                Title: Case Reports in Oncology
                Publisher: S. Karger AG
                ISSN (Electronic): 1662-6575
                Publication date Subscription-year: 2020
                Publication date Collection: September - December 2020
                Publication date (Electronic): 15 October 2020
                Volume: 13
                Issue: 3
                Pages: 1258-1262
                Affiliations
                [_a] aYale University School of Medicine, Yale-New Haven Hospital and Veterans Affairs Connecticut Healthcare System, New Haven, Connecticut, USA
                [_b] bYale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital and Veterans Affairs Connecticut Healthcare System, New Haven, Connecticut, USA
                [_c] cYale University School of Medicine Department of Neurology, New Haven, Connecticut, USA
                [_d] dYale University School of Medicine and Veterans Affairs Connecticut Healthcare System Department of Neurology, New Haven, Connecticut, USA
                [_e] eYale University School of Medicine and Smilowa Cncer Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA
                Author notes
                *Bailey Gleason Fitzgerald, Department of Internal Medicine, Yale School of Medicine, 300 Cedar Street, New Haven, CT 06906 (USA), bailey.fitz@gmail.com
                Article
                Publisher ID: 510743 Other ID: Case Rep Oncol 2020;13:1258–1262
                DOI: 10.1159/000510743
                SO-VID: 6099640d-1349-413a-ade0-dd5f67ed53ea
                Copyright © © 2020 The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 26 July 2020
                Date accepted : 03 August 2020
                Page count
                Figures: 3, Pages: 5
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Keywords: Cranial neuropathies,Leptomeningeal carcinomatosis,Non-small cell lung cancer,BRAF-mutated lung adenocarcinoma
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Pathology, Surgery, Obstetrics & Gynecology, Pharmacology & Pharmaceutical medicine, Hematology
                Keywords: Cranial neuropathies, Leptomeningeal carcinomatosis, Non-small cell lung cancer, BRAF-mutated lung adenocarcinoma

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