Acute lethargy in a young woman due to latent disseminated cancer mimicking bacterial meningitis: a diagnostic pitfall
young woman due to l”>Case Report
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American Journal of Emergency Medicine
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American Journal of Emergency Medicine 34 (2016) 2050.e5-2050.e7
Acute lethargy in a young woman due to latent disseminated cancer mimicking Bacterial meningitis: a Diagnostic pitfall?,??,?,??
Abstract
Leptomeningeal carcinomatosis is an atypical behavior of cancer as a consequence of infiltration of malignant cells into the leptomeninges. Leptomeningeal carcinomatosis may share similar clinical manifesta- tions with other etiologies involving the leptomeninges such as infec- tious meningitis or meningoencephalitis. We present a diagnostic pitfall of acute leptomeningeal carcinomatosis from a latent gastric can- cer in a 28-year-old woman presenting with being rapidly comatose and an initial misdiagnosis of bacterial meningitis. This case report aims to raise Red flags suggesting that when progressive Neurological deterioration mimicking infectious meningitis but with poor responses to empirical antimicrobial therapy are encountered in healthy young in- dividuals, the rare possibility of leptomeningeal carcinomatosis should be considered in the differential diagnosis even if patients have no known malignancy. Cerebrospinal fluid cytology along with gadolinium enhancement magnetic resonance imaging may be critical in the Timely diagnosis and management of these patients with overlapping clinical features.
A 28-year-old woman was admitted to the emergency department with a 5-day history of reduced consciousness, blurry vision, gait distur- bance, and episodic Focal seizures. Her past medical and family histories were unremarkable. Three days before presentation, she had been ad- mitted to a local hospital and received Empiric antibiotics plus anticon- vulsants therapy for suspected Acute bacterial meningitis, but with no clinical improvement.
On arrival, her vital signs were febrile temperature of 37.8?C, pulse rate of 80 per minute, respiratory rate of 18 per minute, and blood pres- sure of 120/80 mmHg. Her conjunctivae were not icteric, clear breath sounds in auscultation, and regular cardiac sounds without pericardial friction rubs. Neurologic examination revealed lethargy with a Glasgow Coma Scale score of 13 (eye opening: 3, best verbal response: 4, and best motor response: 6), bilateral Abducens nerve palsy with funduscopic papilledema, quadriparesis with a Medical Research Council scale of grade 3 to 4, and upper limb dysmetria according to the finger-nose- finger coordination test. Meningeal irritation signs were equivocal. Rou- tine biochemical analyses and toxin screen were within normal limits
? Data sharing: No additional data.
?? Contributorship: All of the authors contributed to planning, conduct, and reporting of
the work. All contributors are responsible for the overall content as guarantors.
?? Competing interests: All of the authors have no conflict of interest.
except for a leukocytosis (White blood cell counts of 15,840/uL; refer- ence value: 4500-11,000/uL) and an elevated C-reactive protein (0.64 mg/dL; reference value: 0.00-0.50 mg/dL). Non-contrast cranial computed tomography obtained at presentation showed insignifi- cant findings. Considering the possibility of acute brainstem infarction or other etiologies, additional gadolinium-enhanced magnetic reso- nance imaging (MRI) of the brain was ordered, which demonstrated diffuse leptomeningeal enhancement in both hemispheres of the cere- brum and cerebellum (FigureA).
A follow-up cerebrospinal fluid (CSF) analysis indicated an elevated opening pressure (30 cm of water), pleocytosis (white blood cell counts of 36/uL), high protein level (72 mg/dL), and low glucose concentration (18 mg/dL). Broad-spectrum antimicrobial agents with ceftriaxone and acyclovir were initiated for presumed infectious meningitis.
On the next day after presentation, the patient gradually became stu- porous and rapidly comatose following a generalized tonic-clonic seizure. Because potential airway compromise and Oxygen desaturation, emer- gency endotracheal intubation with continuous mechanical ventilation was performed. Repeated brain CT demonstrated a global Brain swelling (FigureB). Meanwhile, the microbiologic workup of the blood, CSF, spu- tum, and urine yielded negative findings. Unexpectedly, CSF cytology re- vealed the presence of carcinoembryonic antigen-immunopositive adenocarcinoma. In addition, extremely high levels of carcinoembryonic antigen were detected simultaneously in the CSF (800 ng/mL) and serum (1730 ng/mL), which was consistent with leptomeningeal carcinomato- sis (LMC).
Subsequent investigation of the primary malignancy, which includ- ed chest, abdominopelvic contrast-enhanced CT, and colonoscopy, re- vealed no definite lesions. However, an upper gastroscopy revealed an inconspicuous ulcer on the lesser curvature of the anterior gastric body (FigureC). Pathologic analysis of the resulting biopsy identified the ulcer as a poorly differentiated signet-ring cell adenocarcinoma (FigureD).
From the aforementioned clinical evidences, we confirmed the diag- nosis of acute LMC from an asymptomatic latent gastric cancer in this patient. Palliative treatment with intravenous dexamethasone and glyc- erol was administered for cerebral vasogenic edema. However, the patient’s condition continued to deteriorate throughout her hospital course. Finally, she died 2 weeks after admission.
LMC, also known as carcinomatous meningitis, is an atypical behav- ior of cancer characterized by infiltration of malignant cells into the leptomeninges [1], may present with vertigo, cranial nerve palsies, atax- ia, seizures, Altered consciousness, and ultimately comatose, which could share similar clinical manifestations with other etiologies involv- ing the leptomeninges such as infectious meningitis or meningoenceph- alitis. Patients with these diseases affecting the same anatomical areas
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Figure. A, Gadolinium-enhanced T1-weighted MRI (axial view) showing diffuse linear leptomeningeal enhancements (red arrows) in the cerebellar sulci. B, The cranial CT exhibiting a global brain swelling with effacement of sulci and ventricles. C, The upper gastroscope revealing a subtle gastric ulcer (asterisk) on the lesser curvature of the anterior body of the stomach. D, Histology section demonstrating signet-ring type adenocarcinoma cells (arrows) infiltrating the stroma of the lamina propria of the gastric mucosa (hematoxylin and eosin stain; orig- inal magnification x200). Inset showing immunohistochemical CK18 labeling of signet-ring cells (arrows) in the corresponding stroma (original magnification x200).
but by different pathogenic mechanisms may exhibit overlapping clini- cal features at the First visit to the emergency department, is a diagnostic pitfall. However, misdiagnosis by the emergency physicians results in an inappropriate treatment and may lead to medico-legal problems. In our case, the patient’s course could be explained by involvement of the cortex and Cranial nerves with increased intracranial pressure, con- tributing to diffuse Brain edema, these in turn can precede cerebral and Cerebellar dysfunction [2].
LMC may present in 5% to 8% of patients with a diagnosed hemato- logic or solid malignancy [3,4]. Among malignant solid tumors, LMC oc- curs most commonly in Lung cancer (9%-25%), breast cancer (2%-5%), and melanoma (up to 23%) [1,5]. In contrast, LMC originating from gas- tric cancer is very rare (b 0.16%) [3].
Generally, LMC is rarely considered in healthy Young individuals becoming rapidly comatose. Here, we report an unusual case of acute LMC in a young woman from an uncommon malignant origin and an initial misdiagnosis of bacterial meningitis. Tragically, the ap- parently occult metastatic disease had already progressed by the time of detection [5].
Clues for the diagnosis of LMC are established based on the cytological identification of malignant cells within the CSF in combination with char- acteristic meningeal gadolinium enhancement on craniospinal MRI [3].
Treatments for LMC should be individualized, which include system- ic or intrathecal chemotherapy, radiation therapy, neurosurgery, pallia- tive care, and psychosocial support. The median survival after diagnosis of LMC is only 4 to 6 months, even with aggressive therapy [5].
In conclusion, in cases involving with progressive neurological dys- function resembling Infectious meningoencephalitis but with poor
responses to empiric antimicrobial agents, LMC should be considered in the differential diagnosis even if the patients have no known malignancy.
Tsung-Han Ho, MD Fu-Chi Yang, MD, PhD
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu, 114
Taipei, Taiwan E-mail address: [email protected]
Hung-Wen Kao, MD Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu, 114
Taipei, Taiwan E-mail address: [email protected]
Sy-Jou Chen, MD MS Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu, 114
Taipei, Taiwan E-mail address: [email protected]
Jiunn-Tay Lee, MD Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu, 114
Taipei, Taiwan E-mail address: [email protected]
T.-H. Ho et al. / American Journal of Emergency Medicine 34 (2016) 2050.e5-2050.e7 2050.e7
Liang-Wei Wen, MD Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu, 114
Taipei, Taiwan E-mail address: [email protected]
Heng-Cheng Chu, MD Division of Gastroenterology, Department of Internal Medicine Tri-Service General Hospital, National Defense Medical
Center, No. 325, Section 2 Cheng-Kung Road, Neihu, 114
Taipei, Taiwan E-mail address: [email protected]
Jiann-Chyun Lin, MD, PhD Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu, 114
Taipei, Taiwan
Corresponding author at: Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2 Cheng-Kung Road, Neihu 114, Taipei, Taiwan
Tel.: +886 2 87923311lx12885v; fax: +886 2 87927174
E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2016.02.065
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