The Purple and Ugly Are Hidden Inside

T- cell prolymphocytic leukemia (T-PLL) is a rare, mature lymphoid neoplasm that affects males around age 60 and presents with leukocytosis, lymphadenopathy and hepatosplenomegaly (1-3). Although rare, direct invasion of the CNS can occur (3,4). We describe a case of a 57-year-old male with T-PLL with acute, bilateral, painful vision loss from infiltrative optic neuropathy without optic nerve sheath or CSF involvement

Neuro-Ophthalmic Manifestations of Intracranial Malignancies

Background: To describe the various neuro-ophthalmic presentations, key exam features, and clinical findings associated with 5 common primary and secondary intracranial malignancies. Evidence acquisition: Retrospective PubMed search and review of published case reports, case series, observational studies, book chapters, and review articles examining the neuro-ophthalmic features of intracranial malignancies including primary glial neoplasms (e.g., glioblastoma multiforme), primary and secondary lymphoma, intracranial metastases, carcinomatous/lymphomatous meningitis, and intracranial germ cell tumors. The search strategy used to perform the retrospective review included the aforementioned tumor type (e.g., glioblastoma multiforme) and the following terms and Boolean operators: AND ("visual loss" OR "papilledema" OR "diplopia" OR "ophthalmoplegia" or "neuro-ophthalmology" OR "proptosis"). Results: The rate of growth and the location of an intracranial tumor are essential factors in determining the neuro-ophthalmic presentation of certain intracranial malignancies. Primary malignant brain glial neoplasms commonly present with visual afferent complaints (e.g., unilateral or bilateral visual acuity or visual field defects, bitemporal or homonymous hemianopsia), pupil abnormalities (relative afferent pupillary defect), and optic atrophy or papilledema. Primary intraocular lymphoma (with or without central nervous system lymphoma) typically presents as a painless bilateral vitritis. Secondary intracranial malignancies have variable afferent and efferent visual pathway presentations. Carcinomatous/lymphomatous meningitis is associated with diplopia (e.g., multiple ocular motor cranial neuropathies with or without vision loss from papilledema or compressive/infiltrative optic neuropathy). Intracranial germ cell tumors can present with a chiasmal syndrome or dorsal midbrain syndrome. Conclusion: Intracranial malignancies can present with neuro-ophthalmic symptoms or signs depending on topographical localization. Specific neuro-ophthalmic presentations are associated with different malignant intracranial tumors. Clinicians should be aware of the common malignant intracranial tumors and their associated clinical presentations in neuro-ophthalmology

Incidence of Neurological Complications Secondary to Intrathecal Chemotherapy Used As Either Prophylaxis or Treatment of Leptomeningeal Carcinomatosis

Abstract Purpose: To examine the incidence and frequency of neurological complications secondary to intrathecal chemotherapy. Introduction: Intrathecal (IT) chemotherapeutic agents have a narrow therapeutic index and high potential for toxicity. Though severe side effects are considered rare, consequences of IT chemotherapy administration can be catastrophic. The most common neurotoxic side effect is chemical arachnoiditis, manifesting typically as headache and/or fever, but more severe symptoms have also been reported including paraplegia, cranial nerve palsies, and seizures. The true incidence of neurological complications is not well quantified, and many cases of toxicity may go unrecognized or unreported. Here we detail neurologic complications of IT chemotherapy in adult patients over a two-year time period at our institution. Patients and Methods: Sixty-three patients received IT chemotherapy between January 2014 and December 2015 at Jackson Memorial Hospital and were included in this analysis. We cataloged all neurological complications within four days of IT chemotherapy. We defined minor neurological complications as headache, backache, nuchal rigidity, fever, nausea, or vomiting. Major neurological complications were defined as paresthesia, cranial nerve palsy, paralysis, or asthenia. For each administration of IT chemotherapy we recorded the type and dose of chemotherapy, and results of associated CSF cytology and flow cytometry. Results: Of the 63 patients who received IT chemotherapy treatment, 44 (70%) were male. 20 (32%) patients identified as non-Hispanic, 41 (65%) identified as Hispanic, and 2 (3%) identified as Haitian. The average age at time of treatment was 47.87 years (median: 49, range 22-72). 14 (22%) of patients were HIV positive. At time of IT chemotherapy treatment, 18 (29%) patients had known malignancy present in the CNS. Of the 208 recorded administrations of IT chemotherapy, 197 (95%) included methotrexate and 122 (59%) included cytarabine. The incidence of major neurologic adverse events for all patients receiving IT chemotherapy was 6.8%. The rate of major events was 9.2% for methotrexate with or without hydrocortisone, 9.1% for cytarabine with or without hydrocortisone, and 5.4% for methotrexate and cytarabine combined with or without hydrocortisone. There was no statistically significant difference in rate of major events when the three drug combinations were compared (p=0.562). The rate of minor neurologic events was 38.3% for all cases of patients receiving IT chemotherapy, 42.4% for methotrexate with or without hydrocortisone, 36.4% for cytarabine with or without hydrocortisone, and 35.5% for methotrexate and cytarabine combined with or without hydrocortisone. There was no statistically significant difference in rate of minor events when comparing the three different drug combinations (p=0.604). The adverse events encountered most frequently were headache (15.9%), nausea (13.6%), vomiting (9.6%), back pain (5.8%), and fever (5.8%). The most frequent major adverse events were asthenia (4.3%) and paresthesia (3.8%). Discussion and Conclusion: More than one third of all IT chemotherapy administration events resulted in at least one minor side effect, with roughly 7% resulting in at least one major effect. Headache, nausea, vomiting, back pain, and fever were the most common events encountered-all of which are common sequelae of chemical arachnoiditis. In the cases of major neurologic events we considered potential contamination of the IT methotrexate. Though never confirmed at our institution, Zeng et. al. (J Clin Oncol, 2011) investigated the development of paraplegia amongst patients who received IT methotrexate, discovering trace amounts of vincristine that contaminated intrathecal drugs produced by a manufacturing plant in China causing a large outbreak of severe neurological damage. Murata et al. (J Med Case Rep, 2015) reported a case of demyelination secondary to myelopathy attributed to an IT methotrexate dose. Outbreaks of severe adverse reactions to IT chemotherapy, especially when temporally related, should prompt suspicion of potential chemotherapy contamination. It is important for clinicians to be aware of the adverse events described in this study and consider them seriously when treating patients with IT chemotherapy. * Byrnes D, Dermarkarian C, and Kahn R contributed equally to this work Disclosures No relevant conflicts of interest to declare

Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating Endothelial Progenitor Cells

Background: Endothelial dysfunction, characterized by diminished endothelial progenitor cell (EPC) function and flow-mediated vasodilation (FMD), is a clinically significant feature of heart failure (HF). Mesenchymal stem cells (MSCs), which have pro-angiogenic properties, have the potential to restore endothelial function. Accordingly, we tested the hypothesis that MSCs increase EPC function and restore flow-mediated vasodilation (FMD). Methods: Idiopathic dilated and ischemic cardiomyopathy patients were randomly assigned to receive autologous (n = 7) or allogeneic (n = 15) MSCs. We assessed EPC-colony forming units (EPC-CFUs), FMD, and circulating levels of vascular endothelial growth factor (VEGF) in patients before and three months after MSC transendocardial injection (n = 22) and in healthy controls (n = 10). Findings: EPC-colony forming units (CFUs) were markedly reduced in HF compared to healthy controls (4 ± 3 vs. 25 ± 16 CFUs, P < 0.0001). Similarly, FMD% was impaired in HF (5.6 ± 3.2% vs. 9.0 ± 3.3%, P = 0.01). Allogeneic, but not autologous, MSCs improved endothelial function three months after treatment (Δ10 ± 5 vs. Δ1 ± 3 CFUs, P = 0.0067; Δ3.7 ± 3% vs. Δ-0.46 ± 3% FMD, P = 0.005). Patients who received allogeneic MSCs had a reduction in serum VEGF levels three months after treatment, while patients who received autologous MSCs had an increase (P = 0.0012), and these changes correlated with the change in EPC-CFUs (P < 0.0001). Lastly, human umbilical vein endothelial cells (HUVECs) with impaired vasculogenesis due to pharmacologic nitric oxide synthase inhibition, were rescued by allogeneic MSC conditioned medium (P = 0.006). Interpretation: These findings reveal a novel mechanism whereby allogeneic, but not autologous, MSC administration results in the proliferation of functional EPCs and improvement in vascular reactivity, which in turn restores endothelial function towards normal in patients with HF. These findings have significant clinical and biological implications for the use of MSCs in HF and other disorders associated with endothelial dysfunction