"CNS signs and symptoms, indicative of LM in more than 90% of patients, may be pleomorphic and are often subtle and difficult to distinguish from other cancer or antineoplastic treatment complications . The specificity of gadolinium-enhanced MRI signs is up to 100% in solid tumors, balanced by a risk of false negative as high as 65% and false positive approaching 10% . Evidence of malignant cells in the CSF is diagnostic of LM. "
[Show abstract][Hide abstract] ABSTRACT: Background
The diagnosis of leptomeningeal metastasis (LM) in patients with solid tumors remains difficult. The usual diagnostic methods of cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium enhanced MRI of the entire neuraxis lack both specificity and sensitivity. The Veridex CellSearch® technology has been designed for the detection of circulating tumor cells (CTC) in blood from cancer patients and validated for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer. Our aim was to adapt this technology for the detection and the enumeration of tumor cells in the CSF of breast cancer patients presenting with LM.
On the occasion of a randomized phase III study evaluating the role of the intrathecal treatment in LM from breast cancer (DEPOSEIN, EudraCT N°: 2010-023134-23), the CellSearch® technology was adapted to direct enrichment, enumeration and visualization of tumor cells in 5 mL CSF samples, collected on CellSave® Preservative Tubes and analyzed within 3 days after CSF sampling.
Sixteen CSF of 8 patients with primary breast cancer presenting with LM were studied. EpCAM+/cytokeratin + cells with typical morphology could be observed and enumerated sequentially with reproducible results in low or elevated numbers in 8 patients.
This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of cancer patients with LM, especially to appreciate the efficacy of chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: We report a 76-year-old caucasian man who presented with a 3-week history of progressive confusion. His past medical history included a left nephro-uretectomy for poorly differentiated transitional cell carcinoma 9 years previously. Besides his confusion, his clinical and neurological examination was unremarkable. Extensive investigation revealed only isolated hypoglycorrachia and mildly elevated CSF protein. Cerebral CT and MRI scans without contrast did not reveal any abnormalities. As his condition continued to decline, an MRI scan of the brain with gadolinium was performed which revealed extensive nodular enhancement of the surface of the cerebellum and brainstem and both temporal lobe convexities. Repeat lumbar puncture showed malignant cells in the CSF and confirmed the diagnosis of leptomeningeal carcinomatosis. This case illustrates that leptomeningeal carcinomatosis should be considered in the differential diagnosis of cognitive decline in the elderly, after other common aetiologies have been excluded. The index of suspicion should be increased in patients with a prior history of cancer.
[Show abstract][Hide abstract] ABSTRACT: : Altered mental status is a common reason for neurologic consultation. Although it is often due to a systemic infection or metabolic derangement, a host of other etiologies can lead to irreversible brain injury if they are not promptly identified and treated. A systematic approach to the patient is important, with an understanding of when to initiate a more advanced and potentially more resource-intense diagnostic workup.
: The last decade has seen advances in both the diagnosis and treatment of altered mental status. A significant step forward in the diagnosis of patients with otherwise unexplained encephalitis has been the identification of numerous antibodies associated with paraneoplastic and nonparaneoplastic autoimmune encephalitis. The use of continuous electroencephalography has shown that a significant proportion of otherwise unexplained altered mental status may be caused by nonconvulsive seizures. Several studies have demonstrated that proactive, multicomponent interventions may be effective in preventing hospital-acquired delirium. The recent introduction of dexmedetomidine may lead to decreased rates of delirium in the intensive care unit if the results of clinical trials are borne out in practice.
: This article discusses causes of altered mental status, an initial approach to evaluating the patient, and elements of the advanced diagnostic workup. The article concludes with a general discussion of prevention and treatment.
CONTINUUM Lifelong Learning in Neurology 10/2011; 17(5 Neurologic Consultation in the Hospital):967-83. DOI:10.1212/01.CON.0000407055.17661.33
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