Ryan Y. Kim

MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity

An accurate, nonsurgical diagnostic test for brain tumors is currently unavailable, and the methods of monitoring disease progression are not fully reliable. MicroRNA profiling of biological fluids has recently emerged as a diagnostic tool for several pathologic conditions. Here we tested whether microRNA profiling of cerebrospinal fluid (CSF) enables detection of glioblastoma, discrimination between glioblastoma and metastatic brain tumors, and reflects disease activity. We determined CSF levels of several cancer-associated microRNAs for 118 patients diagnosed with different types of brain cancers and nonneoplastic neuropathologies by quantitative reverse transcription PCR analysis. The levels of miR-10b and miR-21 are found significantly increased in the CSF of patients with glioblastoma and brain metastasis of breast and lung cancer, compared with tumors in remission and a variety of nonneoplastic conditions. Members of the miR-200 family are highly elevated in the CSF of patients with brain metastases but not with any other pathologic conditions, allowing discrimination between glioblastoma and metastatic brain tumors. Quantification of as few as 7 microRNAs in CSF enables differential recognition of glioblastoma and metastatic brain cancer using computational machine learning tools (Support Vector Machine) with high accuracy (91%-99%) on a test set of samples. Furthermore, we show that disease activity and treatment response can be monitored by longitudinal microRNA profiles in the CSF of glioblastoma and non-small cell lung carcinoma patients. This study demonstrates that microRNA-based detection of brain malignancies can be reliably performed and that microRNAs in CSF can serve as biomarkers of treatment response in brain cancers.

Retrospective analysis of the tolerability and activity of lacosamide in patients with brain tumors: clinical article.

OBJECT The object of this study was to determine the tolerability and activity of lacosamide in patients with brain tumors. METHODS The authors reviewed the medical records at 5 US academic medical centers with tertiary brain tumor programs, seeking all patients in whom a primary brain tumor had been diagnosed and who were taking lacosamide. RESULTS The authors identified 70 patients with primary brain tumors and reviewed seizure frequency and toxicities. The majority of the patients had gliomas (96%). Fifty-five (78%) had partial seizures only, and 12 (17%) had generalized seizures. Most of the patients (74%) were started on lacosamide because of recurrent seizures. Forty-six patients (66%) reported a decrease in seizure frequency, and 21 patients (30%) reported stable seizures. Most of the patients (54 [77%]) placed on lacosamide did not report any toxicities. CONCLUSIONS This retrospective analysis demonstrated that lacosamide was both well tolerated and active as an add-on antiepileptic drug (AED) in patients with brain tumors. Lacosamides novel mechanism of action will allow for concurrent use with other AEDs, as documented by its activity across many different types of AEDs used in this patient population. Larger prospective studies are warranted.

Chronic lymphocytic leukemia with central nervous system involvement: report of two cases with a comprehensive literature review

Central nervous system (CNS) involvement is a rare complication of chronic lymphocytic leukemia (CLL) with varied outcomes. We contribute two additional cases of CLL with CNS involvement. The clinical course and response to treatment are described. All 78 previously reported cases of CLL with CNS involvement are presented in this comprehensive review of the literature. CNS involvement of CLL is a rare complication that does not seem to correlate with any evident risk factors. Resolution of CNS symptoms can often be accomplished with intrathecal chemotherapy or irradiation. Early detection and treatment may result in better outcomes in this rare complication.

Levetiracetam-induced interstitial nephritis in a patient with glioma

A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline.

Seizure control: A secondary benefit of chemotherapeutic temozolomide in brain cancer patients.

The severity of brain tumor associated seizures often mirror the growth of the underlying tumor, and may be intractable to conventional antiepileptic drugs. We present a patient with intractable seizures in the setting of a low grade glioma who responded dramatically to temozolomide despite minimal radiographic change in tumor size. Temozolomide is an effective treatment for seizure control in patients with brain tumors.

Cerebral syphilitic gumma: a case report and review of the literature

A 45-year-old male presented with subacute onset of a right-sided hemiparesis, right homonymous hemianopsia, and slurred speech. The brain imaging revealed two separate intraparenchymal enhancing lesions. The cerebrospinal fluid rapid plasma reagin and venereal disease research laboratory test were positive and consistent with syphilitic gumma, and the patient responded dramatically to penicillin G. Despite, currently low incidence of syphilis; CNS gummas should be in the differential of mass lesions as they are eminently treatable.

Paraganglioma with intracranial metastasis: a case report and review of the literature.

Paragangliomas are rare neuroendocrine tumors of neural crest origin. They are mostly benign, however; malignant tumors with aggressive behavior and distant metastasis can also occur. Intracranial involvement is extremely rare and has been sporadically reported in the literature. Here we report a case who presented with progressive neurologic deficits due to multiple intracranial lesions found to be metastasis from an occult retroperitoneal malignant paraganglioma.

Durable remission of leptomeningeal metastases from hormone-responsive prostate cancer

Prostate cancer is rarely associated with leptomeningeal metastasis. An 87-year-old man with a history of prostate cancer presented with leptomeningeal metastasis. He received hormonal therapy with leuprolide. Subsequently, he achieved an impressive response, indicated by a constant fall in his PSA levels and by the stabilization of leptomeningeal disease and clinical improvement. Hormonal therapy may be effective in inducing remission in hormone-sensitive prostate cancer with leptomeningeal metastasis.

Relapsing tumefactive lesion in an adult with medulloblastoma previously treated with chemoradiotherapy and stem cell transplant.

Herein, we present an adult case of medulloblastoma who received chemotherapy, radiation therapy and stem cell transplantation, and underwent multiple surgical resections for what were thought to be recurrences; however pathology confirmed a diagnosis of relapsing tumefactive lesions. This phenomenon seems to be a consequence of stem cell transplantation rather than a simple radiation treatment effect.

Fourth ventricular choroid plexus papilloma

Dear Editors, A 19-year-old girl presented with headache and dizziness over a 6–month-period. The headaches were frontal and postoccipital with dull throbbing quality and she was taking over the counter pain medications. Her headaches did not occur with coughing or straining. She initially thought that this was related to her recent 90 lb weight loss since being on a diet and exercise. She also noted intermittent dizziness accompanied by gait difficulty and a generalized weakness. The week prior to the admission, she had a severe headache, nausea, dizziness, shortness of breath and diffuse weakness. Her physical examination was remarkable for slight bilateral dysmetria, occasional bilateral hypometric saccades, and nystagmus on end gaze. The T1-weighted MRI with gadolinium revealed a heterogeneously enhancing mass fungating into the fourth ventricle and an obstructive hydrocephalus (Fig. 1). The patient underwent surgical resection, and the pathology confirmed a diagnosis of choroid plexus papilloma. Choroid plexus papillomas, which account for about 0.3–0.7 of all intracranial tumors, are more commonly seen in the pediatric population. The most common reported locations are the lateral ventricles (50%), followed by the fourth (40%) and third ventricles (10%) [1–3]. Given their hypervascularity, they usually demonstrate an intense enhancement on postcontrast images [1, 2]. From histopathologic perspective, choroid plexus papillomas are the most common tumor type arising from choroid plexus. Other pathologies include choroid plexus carcinomas and diffuse choroid plexus hyperplasia. Surgical resection is the treatment of choice for choroid plexus papillomas and progression-free survival approaches 100% even despite an incomplete resection [4]. However, choroid plexus carcinomas, which account for about 8–25% of all choroid plexus tumors, have a strong tendency to spread along the cerebrospinal fluid pathway with a variable response to surgery and adjuvant therapy. Hence, it is important to differentiate benign choroid plexus papillomas from this type of tumors [5].