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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 5  |  Page : 1127-1128

Multiple paraneoplastic antibodies (anti-SOX1, anti-Hu, and anti-Amphiphysin) detected in a patient with limbic encephalitis and small cell lung cancer

1 Department of Neurology, Santa Izabel Hospital, Salvador, Brazil
2 Studart and Studart Pathology Laboratory, Santa Izabel Hospital, Salvador, Brazil

Date of Web Publication6-Sep-2017

Correspondence Address:
Thiago Gonçalves Fukuda
Rua Plinio Moscoso, 1233. Salvador
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/neuroindia.NI_1256_15

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How to cite this article:
Fukuda TG, do Rosário MS, Branco RC, Fukuda JS, de Souza e Souza RA, Oliveira-Filho J, de Jesus PA. Multiple paraneoplastic antibodies (anti-SOX1, anti-Hu, and anti-Amphiphysin) detected in a patient with limbic encephalitis and small cell lung cancer. Neurol India 2017;65:1127-8

How to cite this URL:
Fukuda TG, do Rosário MS, Branco RC, Fukuda JS, de Souza e Souza RA, Oliveira-Filho J, de Jesus PA. Multiple paraneoplastic antibodies (anti-SOX1, anti-Hu, and anti-Amphiphysin) detected in a patient with limbic encephalitis and small cell lung cancer. Neurol India [serial online] 2017 [cited 2022 Jan 28];65:1127-8. Available from: https://www.neurologyindia.com/text.asp?2017/65/5/1127/214037


We present the first comprehensive clinical description of a patient with limbic encephalitis associated with small cell lung cancer where three paraneoplastic antibodies were detected.

A 56-year old man presented at the emergency department with a 2-month history of cognitive and behavioral changes associated with motor disturbances. His family mentioned that the clinical course began with memory lapses that progressed to impairment of anterograde memory and concomitant behavioral changes characterized by sexual disinhibition and aggressiveness. The motor abnormalities began with difficulty to grasp certain objects with his hands, progressing to abnormal finger posture and involuntary movements of the arms and left hand [Figure 1]a. He was a heavy cigarette smoker and consumed alcohol socially. His past medical history included hypertension, diabetes mellitus, and dyslipidemia.
Figure 1: Abnormal left hand dystonic posture (a). FLAIR hyperintensity involving bilateral medial temporal lobes, insular cortex, and inferolateral frontal lobes. (b) PET showing increased uptake in the right hilar lymph nodes (c and d)

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During the admission, the patient was very aggressive and was using inappropriate speech. After admission, severe insomnia and signs of dysautonomia were observed (tachycardia, sweating), followed by development of seizures.

Routine laboratory tests were normal, except for a mild hyponatremia (130 mmol/l). A brain magnetic resonance imaging (MRI) was performed, which demonstrated a limbic lobe hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging [Figure 1]b. Electroencephalography only showed generalized slowing of waves. Cerebrospinal fluid (CSF) analysis was normal, and polymerase chain reaction (PCR) test for herpes virus was also negative. Computed tomography (CT) of the chest revealed hilar lymphadenopathy with a necrotic center without lung parenchymal involvement. Positron emission tomography (PET) showed increased uptake in the right hilar lymph nodes [Figure 1]c and [Figure 1]d. Blood and CSF were sent for analyses of paraneoplastic antibodies, and both the samples were positive for Hu, Amphiphysin, and SOX1. Mediastinoscopy was performed, and three excisional hilar lymph nodes biopsies were performed. Pathologic anatomy revealed that one of the lymph nodes had the involvement of small cell neuroendocrine lung carcinoma [Figure 2].
Figure 2: Pathologic patterns of the mediastinal lymph nodes: (a) Hematoxylin and eosin (H and E) staining, magnification 100×; small cell neoplasm with scant cytoplasm and nuclei with granular chromatin. (b) H and E staining, 400 × magnification; small cell neoplasm with scant cytoplasm and nuclei with granular chromatin and evident mitosis. (c-e) Immunofluorescence with positivity for synaptophysin, AE1AE3, (cytokeratin), and chromoganin, respectively, which favors the diagnosis of small-cell neuroendocrine carcinoma. (f) Positivity for KI-67, which indicates a cell proliferation index higher than 20%

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We decided to initiate immunotherapy with intravenous steroids, intravenous immunoglobulin, plasmapheresis, and cyclophosphamide; there was no clinical improvement. Chemotherapy as well as radiotherapy were administered; however, the patient developed pulmonary sepsis and died.

The finding of highly specific antibodies directed against onconeural antigens has revolutionized the diagnosis and promoted the understanding of these syndromes, leading to the current hypothesis of an autoimmune pathophysiology. Detection of two or more paraneoplastic antibodies in the same patient is an uncommon event. There are few reports that describe the association of Lambert Eaton myasthenic syndrome (LEMS) plus limbic encephalitis or cerebellar degeneration.[1],[2] The onconeural antibodies profile reported in these cases were the association of the anti-VGCC (voltage gated calcium channel) plus anti LGl1 or anti- SOX 1 (Sry-like high mobility box).[2] There are a few reports of the co-existence of LEMS with anti-Hu-antibody associated limbic encephalitis. All of these papers attributed it to confirmed or highly-suspected small cell lung cancer.[3],[4]

Our report is the first complete clinical description of a patient with limbic encephalitis with three paraneoplastic antibodies detected, namely, anti-SOX1, anti-Hu, and Amphiphysin (without stiff-person syndrome).

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There are no conflicts of interest.

 » References Top

Kalra S, Gozzard P, Jacob S, Leonard A, Maddison P. Limbic encephalitis and Lambert Eaton myasthenic syndrome – An immunological profile of a new syndrome. Clin Neurol Neurosurg 2014;116:99-100.  Back to cited text no. 1
Mason WP, Graus F, Lang B, Honnorat J, Delattre JY, Valldeoriola F, et al. Small- cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert–Eaton myasthenic syndrome. Brain 1997;120:1279-300.  Back to cited text no. 2
Titulaer MJ, Klooster R, Potman M, Sabater L, Graus F, Hegeman IM, et al. SOX antibodies in small-cell lung cancer and Lambert–Eaton myasthenic syndrome: Frequency and relation with survival. J Clin Oncol 2009;27:4260-7.  Back to cited text no. 3
Pittock SJ, Lucchinetti CF, Parisi JE, Benarroch EE, Mokri B, Stephan CL, et al. Amphiphysin autoimmunity: Paraneoplastic accompaniments. Ann Neurol 2005;58:96-107.  Back to cited text no. 4


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