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A case of limbic encephalitis presenting as a paraneoplastic manifestation of limited stage small cell lung cancer: a case report
© Fahim et al; licensee BioMed Central Ltd. 2010
Received: 18 January 2010
Accepted: 17 December 2010
Published: 17 December 2010
The differential diagnosis of altered mental status and behavioral change is very extensive. Paraneoplastic limbic encephalitis is a rare cause of cognitive impairment, which should be considered in the differential diagnosis.
A 64-year-old British Caucasian woman presented to our hospital with a 12-week history of confusion and short-term memory loss. She was hyponatremic with a serum sodium level of 128mmol/L. Moreover, there was evidence of left hilar prominence on the chest radiograph. A thoracic computed tomography scan showed left hilar opacity with confluent lymphadenopathy. A percutaneous biopsy confirmed a diagnosis of small cell lung cancer. There was no radiological evidence of brain metastasis on the computed tomography scan. In view of continued cognitive impairment, which was felt to be disproportionate to hyponatremia, a magnetic resonance imaging scan of the brain was undertaken. It showed hyperintense signals from both hippocampi, highly suggestive of limbic encephalitis presenting as a paraneoplastic manifestation of small cell lung cancer. She had a significant radiological and clinical response following chemotherapy and radiotherapy.
This case highlights the importance of considering paraneoplastic syndromes in patients with neurological symptoms in the context of lung malignancy. If initial investigations fail to reveal the cause of cognitive impairment in a patient with malignancy, magnetic resonance imaging may be invaluable in the diagnosis of limbic encephalitis. The clinical presentation, diagnostic techniques and management of paraneoplastic limbic encephalitis are discussed in this case report.
The differential diagnosis of cognitive impairment in a patient with lung malignancy is extensive. Paraneoplastic neurological syndromes, including limbic encephalitis, should be suspected as a cause of altered behavior and short-term memory loss, if the more common causes (brain metastasis, biochemical derangement, infection or drug related delirium) have been excluded. We report a case of paraneoplastic limbic encephalitis (PLE) associated with limited stage small cell lung cancer, which highlights the importance of considering this entity as a cause of cognitive dysfunction in a patient with lung carcinoma.
A 64-year-old British Caucasian woman with a medical history of fibromyalgia, hypertension and asthma presented to our hospital with collapse and brief loss of consciousness. Our patient had no recollection of the event, and she did not have a history of witnessed seizures. According to her family, she had experienced progressively worsening short-term memory for the previous three months. She was a lifelong smoker with a 50-pack-year history. Her medications included citalopram, co-amilozide, salbutamol and beclomethasone inhalers.
Paraneoplastic limbic encephalitis, first described as a clinical entity in 1968  is characterized by short-term memory deficits, mood and behavioral changes and relative preservation of other cognitive functions. There may be seizures, which are most often partial complex in nature. Moreover, hypothalamic involvement can manifest with hyperthermia, hyperphagia or pituitary hormonal deficits . Patients with PLE often present with symptoms of neurological involvement distant from the limbic system (commonly brainstem and cerebellum). Bakheit and colleagues  found that only 32% of patients had isolated limbic encephalitis. The neurological symptoms often precede identification of the tumor by weeks or months and the non-specific nature and diversity of symptoms add to the difficulty in diagnosing this rare clinical entity.
The most frequent neoplasms associated with PLE are small cell lung cancer, testicular tumors, thymoma, Hodgkin's lymphoma and breast cancer. In an analysis of 50 patients with PLE, Gultekin and colleagues  found that lung cancer was the most common neoplasm identified in 50% of cases, followed by testicular and breast carcinoma in 20% and 8%, respectively. The neurological symptoms preceded the diagnosis of cancer in approximately two-thirds of patients with a median duration of three and a half months.
Paraneoplastic limbic encephalitis can pose a diagnostic challenge in patients with cognitive impairment, especially when there is no evidence of malignant disease, and can be easily mistaken for viral encephalomyelitis or rapidly progressive neurodegenerative disease. Even in the presence of malignancy, the neurological symptoms can be easily attributed to cranial metastases.
An MRI scan of the brain is the most sensitive radiological investigation to diagnose limbic encephalitis. Typically, it shows hyperintense lesions in the medial temporal lobes and these are best visualized in T2 and axial FLAIR sequences without significant contrast enhancement. A CSF examination is seldom diagnostic of this condition, and the most common findings are consistent with inflammatory changes (pleocytosis, increased protein, oligoclonal bands and increased immunoglobulin content). Anti-neuronal antibodies are frequently found in the serum or CSF of patients with PLE, but the absence of these antibodies does not exclude the diagnosis. The most common is the anti-Hu antibody, which is present in about 50% of patients with small cell lung cancer presenting with limbic encephalitis and the anti-Ta antibody associated with testicular cancer . Moreover, the presence of antibodies can be predictive for a good response to immunosuppressive therapy .
Electroencephalography can be a useful tool in order to support the diagnosis of limbic encephalitis, as it can demonstrate focal or generalized slowing and/or sharp wave epileptiform activity predominantly in the temporal regions . The treatment should be directed at the associated malignancy, which frequently improves the neurological symptoms and is superior to immunomodulatory therapy.
Our patient's case highlights the importance of considering PLE in the differential diagnosis of altered mental status in patients with lung malignancy, if there is no readily identifiable cause of cognitive impairment on initial investigations. Prompt diagnosis and early treatment of malignancy provides the best chance of clinical improvement in patients with this rare disorder.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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