Case Report | Open Access | Peer Reviewed

Paraneoplastic Limbic Encephalitis in a Patient with Small Cell Lung Cancer: A Case Report

Mohyeldin S Abdelhalim1, Mohamed Elfil2*, Nada Hassan3, Abdelsalam A Ismail1

1 Department of Clinical Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

2 Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA

3 Department of Radiodiagnosis, Faculty of Medicine, Alexandria University, Alexandria, Egypt

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ABSTRACT

Paraneoplastic limbic encephalitis (PLE) is a rare paraneoplastic syndrome that occurs in certain types of cancer. Its pathophysiology is thought to be autoimmune and might be associated with autoantibodies directed against different neuronal cell structures. However, not all PLE patients test positive for these autoantibodies and medical literature suggests a few criteria to confirm the diagnosis. In this case report, a male patient presented with respiratory symptoms, and the computed topography (CT) showed an infiltrative mass in the chest, yet no masses were seen elsewhere in the body including the brain. The patient was admitted, and a biopsy was obtained from the chest mass. During admission, he developed disorientation, slow response and stupor. The laboratory workup revealed severe hyponatremia, and the magnetic resonance imaging (MRI) findings were suggestive of PLE. The patient was managed by supportive treatments targeting PLE and hyponatremia, and chemoradiotherapy for his small cell lung cancer (SCLC).

KEYWORDS

small cell lung cancer, paraneoplastic limbic encephalitis, PLE, neuroinflammation

INTRODUCTION

Paraneoplastic neurological syndromes are considered to be rare complications occurring in cancer patients.1 They represent a challenging problem in this patient population as they might present with a wide variety of clinical conditions and manifestations such as encephalitis, Lambert-Eaton syndrome2 and myelopathies.3 The underlying pathophysiology of these syndromes is believed to be autoimmune in nature and not related to direct tumor invasion, secondary metastasis or treatment adverse effects.4 PLE is one of these syndromes that is commonly seen in lung cancer patients, especially small cell lung carcinoma5, testicular cancer6-8 and breast cancer.9 PLE typically affects hippocampus, hypothalamus and/or amygdala as the main structures of the limbic system.10 Patients with PLE may present with cognitive impairment, personality changes, hallucinations, limbic paresis, seizures, disturbed consciousness and/or memory problems.11-14 In this report, we present a case of PLE in a male patient with SCLC, and we also demonstrate how we managed the patient according to the current evidence in medical literature.

CASE PRESENTATION

A 55-year old male patient presented with cough, chest tightness, and dyspnea on effort. He had a history of smoking one pack of cigarettes per day for 22 years. CT scans of the patient’s brain, neck, chest, abdomen and pelvis revealed a left hilar mass lesion targeting the distal left main bronchus as well as its upper and lower lobar divisions with multiple pathologically enlarged confluent mediastinal nodal masses located at the pre-vascular, bilateral para-tracheal, aortopulmonary and subcarinal regions (Figure 1) with no metastasis elsewhere in the body. The patient was admitted, and a core biopsy was taken from the patient’s left hilar mass lesion for histopathological examination that later on showed SCLC.

FIGURE 1 Axial chest CT scan showing left hilar mass lesion targeting the distal left main bronchus.

Before getting the histopathological results and on the fourth day of admission, the patient developed stupor, slow verbal response and disorientation. Chest and abdominal physical examination did not show any significant finding, and the neurological examination showed symmetric pupils with normal light reflex. Deep tendon reflexes were normal with negative Babinski, Brudzinski and Kernig signs. The laboratory testing revealed a hemoglobin level of 11.8 g/dl, a white blood cell (WBC) count of 11,500/µL, a platelet count of 141,000/µL and a blood glucose level of 176 mg/dl. The initial serum sodium level was 118 mg/dl. The C-reactive protein level, liver function test, urinalysis and electrocardiogram showed no abnormalities. The cerebrospinal fluid (CSF) analysis revealed an opening pressure of 92 mmH2O, a WBC count of 20/µL (lymphocyte 83%), a protein level of 52 mg/dl, a glucose level of 112 mg/dl and negative cytology. MRI of the brain showed a hyperintense signal, noticed by T2 and Fluid-attenuated inversion recovery (FLAIR) imaging techniques, at the right insular cortex (Figure 2) and some of the gyri at the right frontoparietal convexity with mild swelling (Figure 3). The right corpus striatum, the right thalamus as well as the right cingulate gyrus showed mild bright signal on diffusion-weighted imaging (DWI), yet no frank diffusion restriction was noticed (Figure 4). These imaging findings were suggestive of right sided limbic encephalitis. Furthermore, on electroencephalogram (EEG), there were epileptiform discharges from right frontotemporal area with disorganization and slowing of background activity.

FIGURE 2 Axial FLAIR MRI sequence showing hyperintensities at right insular gyrus, right thalamus, right corpus striatum, and right cingulate gyrus.

FIGURE 3 Axial FLAIR MRI sequence showing hyperintense signal at some of the right frontoparietal gyri.

FIGURE 4 Axial DWI MRI sequence showing a bright signal at the insular gyrus.

After 2 weeks of dexamethasone and gradual correction of hyponatremia by hypertonic saline infusion at the intensive care unit, the patient showed gradual improvement of his mental status and was transferred to regular ward. However, the patient also had significant weight loss of 15 kilograms after diagnosis of SCLC, and profound muscle wasting.

The decision was made to start radiotherapy with concomitant platinum-based doublet chemotherapy (etoposide plus carboplatin), which led to significant improvement of his respiratory symptoms and mental status but before the end of the third week of radiotherapy, the patient encountered bacterial bronchopneumonia and consequently septic shock and passed away.

DISCUSSION

            PLE is a rare condition that is thought to be etiologically autoimmune in patients suffering from a few types of cancer, most commonly lung cancer15, which are associated with the production of several types of onconeuronal autoantibodies directed against certain antigens in the neuronal cells including ion channels, cytoplasmic and nuclear antigens.14 According to the profile of such autoantibodies, the extent and the severity of PLE may vary from one patient to another.16 However, the exact pathophysiology by which such onconeuronal autoantibodies can ultimately lead to PLE is not fully understood up till now.17 It is to be taken into consideration that not all cancer patients who test positive for any of these antibodies develop PLE.18 Moreover, such autoantibodies can still be not found in a considerable proportion of PLE patients.19 Thus, the diagnosis of PLE is considered to be difficult as biological markers are not positive in all cases, and also other neuro-oncological complications should be excluded before concluding this diagnosis. Following exclusion of other neuro-oncologic complications, PLE diagnosis can be suspected in patients presenting with the suggestive manifestations and have MRI abnormalities, abnormal activity in the temporal lobe on EEG and/or inflammatory profile of the CSF analysis.14-15

            In this case report, our patient presented with respiratory symptoms -cough, chest tightness and dyspnea- and the CT scans revealed a suspicious infiltrating mass in the chest, that was later on confirmed to be SCLC by histopathologic examination of the biopsy sample. Additionally, the CT scans of the brain, neck, abdomen and pelvis confirmed no metastasis elsewhere in the body. Yet while admitted, our patient developed disorientation, stupor and delayed verbal response during communication. A full workup showed the abovementioned MRI findings, abnormal epileptiform activity in the frontotemporal area on EEG, an elevated WBC count in the CSF with negative cytology for cancer cells and severe hyponatremia. While the severe hyponatremia alone could have explained the neurological symptoms the patient developed during admission20, a decision was made to do an MRI of the brain to exclude any other serious condition, and the findings were suggestive of PLE. For the treatment of PLE, the current literature recommends managing the tumor either by chemo/radiotherapy or by surgery 13,21 to eliminate the main source of the paraneoplastic syndrome. Also, supportive treatment is required, and the options include high doses of steroids, intravenous immunoglobulins and plasma exchange.22,23 Therefore, our patient was initially treated for both hyponatremia and PLE, as he received gradual infusion of hypertonic saline for the hyponatremia and dexamethasone for PLE before starting the chemoradiotherapy regimen for the SCLC. The supportive treatment improved the patient’s mental status together with the subsequent chemoradiotherapy which also improved the respiratory symptoms the patient was suffering from.

TAKE-HOME LESSONS

            In patients with certain types of cancer, especially SCLC, physicians should be very cautious if a patient develops neurological manifestations despite the absence of brain metastasis. PLE could explain these manifestations if the workup, including lab testing and brain imaging, met the criteria for the diagnosis. In our patient’s case, laboratory testing revealed severe hyponatremia which could have explained the patient’s neurological symptoms. However, an MRI of the brain was done to rule out any serious complication, and the findings were suggestive of PLE, which actually implies that in individual cases, it might be beneficial to keep a low threshold for suspecting PLE diagnosis even if clinical scenario was not 100% going in this direction.

CONCLUSION

            PLE is a rare paraneoplastic syndrome that can take place in patients with certain types of cancer, especially lung cancer and it is not related to any tumor invasion, secondary metastasis or side effects of cancer treatment. Our patient suffered from SCLC and developed the neurological symptoms that raised the suspicion for PLE during admission. While the lab testing showed severe hyponatremia that could have explained the patient’s manifestations, MRI, EEG and CSF analysis demonstrated findings consistent with PLE and the patient was managed accordingly, and both the chemoradiotherapy and the supportive treatment improved the patient’s neurological symptoms. Thus, it is extremely important to efficiently assess any neurological symptoms in cancer patients and manage these symptoms according to their etiology.

DISCLOSURES

  1. S. Abdelhalim reports no conflict of interest.
  2. Elfil reports no conflict of interest.
  3. Hassan reports no conflict of interest.
  4. A. Ismail reports no conflict of interest.

TABLES & FIGURES

FIGURE 1 Axial chest CT scan showing left hilar mass lesion targeting the distal left main bronchus.

FIGURE 2 Axial FLAIR MRI sequence showing hyperintensities at right insular gyrus, right thalamus, right corpus striatum, and right cingulate gyrus.

FIGURE 3 Axial FLAIR MRI sequence showing hyperintense signal at some of the right frontoparietal gyri.

FIGURE 4 Axial DWI MRI sequence showing a bright signal at the insular gyrus.

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Conflict of Interest
There is no conflict of interest to declare.

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