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A Case of Confusion
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI A Case of Confusion Ishita Aggarwal, Jared Beller, and Dmitrios Tzimas NYU School of Medicine and Bellevue Hospital, New York, New York
Question: A 59-year-old man with a history of hypertension, hyperlipidemia, diabetes mellitus type 2, chronic kidney disease, and chronic right foot osteomyelitis was found confused in his car by a passerby and was admitted for altered mental status and new memory deficits. He was only oriented to himself. He had anterograde amnesia and could not recall information for >1–2 hours at a time. He had diarrhea that was believed to be overflow related. He denied abdominal pain, bright red blood per rectum, nausea, vomiting, loss of appetite, and was unsure of weight loss. Physical examination was significant for a weeping yellow ulcer on the right malleolus. No mass was palpated on rectal examination, although there was mucous and liquid stool in the vault. Laboratory values were significant for a white blood cell count of 23,600/mm3 (77% neutrophils, 11% monocytes, 13% lymphocytes), hemoglobin of 7.5 g/dL, creatinine of 2.3 mg/dL, erythrocyte sedimentation rate of 87 mm/h. Chest radiograph was unremarkable. Computed axial tomography (CAT) of the head did not indicate an acute intracranial abnormality. He initially received normal saline, vancomycin, ceftriaxone, piperacillin/tazobactam, and acyclovir in the emergency department. Bacterial meningitis was ruled out with cerebrospinal fluid studies so the patient was admitted for the workup of his altered mental status and for treatment of osteomyelitis. Laboratory evaluation for herpes simplex virus (HSV)-1, HSV-2, varicella zoster virus, Epstein–Barr virus, cytomegalovirus, West Nile virus, alpha-fetoprotein, beta-human chorionic gonadotropin, Lyme disease, Mycobacterium tuberculosis, VRDL, rapid plasma reagin, Clostridium difficile, and stool ova and parasite, was unrevealing. MRI of the brain revealed bilateral hyperintensities in the mesial temporal lobes (Figure A). Repeat cerebrospinal fluid studies and serum studies were done to evaluate possible paraneoplastic and antibody-mediated etiologies. Further workup for an occult malignancy with chest, abdomen and pelvis CT scan and MRI revealed a large, 7 5-cm sigmoid mass with no evidence of metastases (Figure B). On subsequent colonoscopy, a circumferential, ulcerated and necrotic mass was found extending from 10 cm to approximately 20 cm from the anal verge, and occupied 75% of the lumen. The remainder of the colon was free of gross abnormality. Biopsies of the colonic mass were taken (Figure C; original magnification, 20). What diagnosis can be made after this presentation of clinical, laboratory, imaging, and histopathologic findings? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.06.036
Gastroenterology 2014;147:e5–e6
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI Answer to the Clinical Challenges and Images in GI Question: Image 3: Paraneoplastic Limbic Encephalitis The pathologic findings were consistent with moderately differentiated invasive adenocarcinoma of the sigmoid and rectum. Neuroimaging and the patient’s clinical picture were consistent with limbic encephalitis. Limbic encephalitis is characterized by a subacute onset of confusion with a marked reduction of short-term memory.1 Our patient met the criteria of paraneoplastic limbic encephalitis with his profound short-term memory impairment, malignancy within 4 years of neurologic manifestations, and exclusion of other neurooncologic complications and cerebrospinal fluid with inflammation; he had few oligoclonal bands, but negative cytology.2 The patient was admitted for intravenous antibiotics to treat his right calcaneal osteomyelitis, and was concurrently treated with chemoradiation with 5-flurouracil as an inpatient for stage IIA rectal cancer. Later, he underwent a low anterior resection. Interestingly, the patient’s paraneoplastic markers from the serum and cerebrospinal fluid (anti-GAD65, Hu, Yo, Ri, MaTa, CV2, CASP, NMDA-R, VGKC, amphiphysin and LGII) were normal. Sio et al3 reported a case of a man who presented with visual disturbances, generalized headaches, hypersomnolence, urinary retention, and confusion with a negative infectious workup but this patient required FOLFOX chemotherapy, steroids, and ultimately hemicolectomy before his symptoms improved.3 They hypothesized that there are perhaps unidentified autoantibodies implicated in limbic encephalitis that may be present.3 Paraneoplastic syndromes associated with occult malignancies are more common in lung, testicular and breast cancers.1,2 As in our patient, paraneoplastic neurologic manifestations often develop before the diagnosis of cancer by several months in 80% of patients.1 Treatment generally consists of treating the underlying cancer to remove the origin of the antibodies, although our patient was experiencing some neurologic improvement before the start of his chemotherapy. In some patients, immunosuppression with steroids, intravenous immunoglobulin, plasma exchange, or cyclophosphamide has been useful.1
References 1. 2. 3.
e6
Said S, Cooper CJ, Reyna E, et al. Paraneoplastic limbic encephalitis, an uncommon presentation of a common cancer: case report and discussion. Am J Case Rep 2013;14:391–394. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123:1481–1494. Sio TT, Paredes M, Chaudhary U. Neurologic manifestation of colonic adenocarcinoma. Rare Tumors 2012;4:98–100.
Question: A 59-year-old man with a history of hypertension, hyperlipidemia, diabetes mellitus type 2, chronic kidney disease, and chronic right foot osteomyelitis was found confused in his car by a passerby and was admitted for altered mental status and new memory deficits. He was only oriented to himself. He had anterograde amnesia and could not recall information for >1–2 hours at a time. He had diarrhea that was believed to be overflow related. He denied abdominal pain, bright red blood per rectum, nausea, vomiting, loss of appetite, and was unsure of weight loss. Physical examination was significant for a weeping yellow ulcer on the right malleolus. No mass was palpated on rectal examination, although there was mucous and liquid stool in the vault. Laboratory values were significant for a white blood cell count of 23,600/mm3 (77% neutrophils, 11% monocytes, 13% lymphocytes), hemoglobin of 7.5 g/dL, creatinine of 2.3 mg/dL, erythrocyte sedimentation rate of 87 mm/h. Chest radiograph was unremarkable. Computed axial tomography (CAT) of the head did not indicate an acute intracranial abnormality. He initially received normal saline, vancomycin, ceftriaxone, piperacillin/tazobactam, and acyclovir in the emergency department. Bacterial meningitis was ruled out with cerebrospinal fluid studies so the patient was admitted for the workup of his altered mental status and for treatment of osteomyelitis. Laboratory evaluation for herpes simplex virus (HSV)-1, HSV-2, varicella zoster virus, Epstein–Barr virus, cytomegalovirus, West Nile virus, alpha-fetoprotein, beta-human chorionic gonadotropin, Lyme disease, Mycobacterium tuberculosis, VRDL, rapid plasma reagin, Clostridium difficile, and stool ova and parasite, was unrevealing. MRI of the brain revealed bilateral hyperintensities in the mesial temporal lobes (Figure A). Repeat cerebrospinal fluid studies and serum studies were done to evaluate possible paraneoplastic and antibody-mediated etiologies. Further workup for an occult malignancy with chest, abdomen and pelvis CT scan and MRI revealed a large, 7 5-cm sigmoid mass with no evidence of metastases (Figure B). On subsequent colonoscopy, a circumferential, ulcerated and necrotic mass was found extending from 10 cm to approximately 20 cm from the anal verge, and occupied 75% of the lumen. The remainder of the colon was free of gross abnormality. Biopsies of the colonic mass were taken (Figure C; original magnification, 20). What diagnosis can be made after this presentation of clinical, laboratory, imaging, and histopathologic findings? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.06.036
Gastroenterology 2014;147:e5–e6
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI Answer to the Clinical Challenges and Images in GI Question: Image 3: Paraneoplastic Limbic Encephalitis The pathologic findings were consistent with moderately differentiated invasive adenocarcinoma of the sigmoid and rectum. Neuroimaging and the patient’s clinical picture were consistent with limbic encephalitis. Limbic encephalitis is characterized by a subacute onset of confusion with a marked reduction of short-term memory.1 Our patient met the criteria of paraneoplastic limbic encephalitis with his profound short-term memory impairment, malignancy within 4 years of neurologic manifestations, and exclusion of other neurooncologic complications and cerebrospinal fluid with inflammation; he had few oligoclonal bands, but negative cytology.2 The patient was admitted for intravenous antibiotics to treat his right calcaneal osteomyelitis, and was concurrently treated with chemoradiation with 5-flurouracil as an inpatient for stage IIA rectal cancer. Later, he underwent a low anterior resection. Interestingly, the patient’s paraneoplastic markers from the serum and cerebrospinal fluid (anti-GAD65, Hu, Yo, Ri, MaTa, CV2, CASP, NMDA-R, VGKC, amphiphysin and LGII) were normal. Sio et al3 reported a case of a man who presented with visual disturbances, generalized headaches, hypersomnolence, urinary retention, and confusion with a negative infectious workup but this patient required FOLFOX chemotherapy, steroids, and ultimately hemicolectomy before his symptoms improved.3 They hypothesized that there are perhaps unidentified autoantibodies implicated in limbic encephalitis that may be present.3 Paraneoplastic syndromes associated with occult malignancies are more common in lung, testicular and breast cancers.1,2 As in our patient, paraneoplastic neurologic manifestations often develop before the diagnosis of cancer by several months in 80% of patients.1 Treatment generally consists of treating the underlying cancer to remove the origin of the antibodies, although our patient was experiencing some neurologic improvement before the start of his chemotherapy. In some patients, immunosuppression with steroids, intravenous immunoglobulin, plasma exchange, or cyclophosphamide has been useful.1
References 1. 2. 3.
e6
Said S, Cooper CJ, Reyna E, et al. Paraneoplastic limbic encephalitis, an uncommon presentation of a common cancer: case report and discussion. Am J Case Rep 2013;14:391–394. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123:1481–1494. Sio TT, Paredes M, Chaudhary U. Neurologic manifestation of colonic adenocarcinoma. Rare Tumors 2012;4:98–100.