Rapid and Deep Remission Induced by Blinatumomab for CD19-Positive Chronic Myeloid Leukemia in Lymphoid Blast Phase

In summary, we show rapid and deep remission induced by blinatumomab in CD19(+) blast phase CML. Clinicians may consider the use of bispecific T-cell engager therapy as a bridge to transplant. Additional studies are needed before expanding the US Food and Drug Administration indication of blinatumomab to include lymphoid blast phase CML

Intramedullary melanotic schwannoma

We present a case of an intramedullary melanotic schwannoma (IMS) of the thoracic spinal cord. To our knowledge, this is the seventh reported case of an IMS of the central nervous system. Schwannomas are benign nerve sheath tumors of neural crest origin composed entirely of well differentiated Schwann cells that typically occur in peripheral nerves. Both the intramedullary location and the melanotic component of the reported lesion make it exceedingly rare. We will present our case, theories as to the origin of these tumors, clues in radiographic identification, and current clinical follow-up recommendations

Non-genomic effects of nuclear receptors: insights from the anucleate platelet

Nuclear receptors have the ability to elicit two different kinds of responses, genomic and non-genomic. While genomic responses control gene expression by influencing the rate of transcription, non-genomic effects occur rapidly and independently of transcriptional regulation. Due to their anucleate nature and mechanistically well-characterised and rapid responses, platelets provide a model system for the study of any non-genomic effects of the nuclear receptors. Several nuclear receptors have been found to be expressed in human platelets, and multiple nuclear receptor agonists have been shown to elicit anti-platelet effects by a variety of mechanisms. The non-genomic functions of NRs vary, including the regulation of kinase and phosphatase activity, ion channel function, intracellular calcium levels and production of second messengers. Recently, the characterisation of mechanisms and identification of novel binding partners of nuclear receptors have further strengthened the prospects of developing their ligands into potential therapeutics that offer cardio-protective properties in addition to their other defined genomic effects

Refractory Cerebrospinal Fluid Rhinorrhea Secondary to Occult Superior Vena Cava Syndrome and Benign Intracranial Hypertension: Diagnosis and Management

Objective: This study is designed to describe the association between benign intracranial hypertension (BIH) and spontaneous cerebrospinal fluid (CSF) rhinorrhea and address the effect of extracranial venous flow dynamics on intracranial pressure (ICP). Methods: We present a 58-year-old woman with refractory spontaneous CSF rhinorrhea who was later found to have superior vena cava syndrome. The patient had undergone two prior transnasal endoscopic repair attempts. In retrospect, a preoperative magnetic resonance venogram (MRV) suggested very prolonged cerebral transit time, despite otherwise normal intracranial venous anatomy. Results: The CSF leak was repaired through a bifrontal craniotomy. The intraoperative and postoperative course was complicated due to the patient's significant comorbidities. She ultimately made a good recovery and has not had any further CSF rhinorrhea in more than 2 years of follow-up. Conclusions: Refractory, spontaneous CSF leak must prompt aggressive investigation for multiple causes of elevated ICP. A cerebral transit time can be obtained from scout imaging when a magnetic resonance angiogram or MRV is performed, and this may disclose elevated ICP if it is prolonged. If endoscopic transnasal repair fails, craniotomy and direct suture repair and autologous tissue reinforcement of the skull base may prove successful and durable, even if BIH persists

Evolution of deep brain stimulation: Human electrometer and smart devices supporting the next generation of therapy

Deep brain stimulation (DBS) provides therapeutic benefit for several neuropathologies, including Parkinson disease (PD), epilepsy, chronic pain, and depression. Despite well-established clinical efficacy, the mechanism of DBS remains poorly understood. In this review, we begin by summarizing the current understanding of the DBS mechanism. Using this knowledge as a framework, we then explore a specific hypothesis regarding DBS of the subthalamic nucleus (STN) for the treatment of PD. This hypothesis states that therapeutic benefit is provided, at least in part, by activation of surviving nigrostriatal dopaminergic neurons, subsequent striatal dopamine release, and resumption of striatal target cell control by dopamine. While highly controversial, we present preliminary data that are consistent with specific predications testing this hypothesis. We additionally propose that developing new technologies (e.g., human electrometer and closed-loop smart devices) for monitoring dopaminergic neurotransmission during STN DBS will further advance this treatment approach. © 2009 International Neuromodulation Society

Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) for intraoperative neurochemical monitoring

The Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) measures extracellular neurotransmitter concentration in vivo and displays the data graphically in nearly real time. WINCS implements two electroanalytical methods, fast-scan cyclic voltammetry (FSCV) and fixed-potential amperometry (FPA), to measure neurotransmitter concentrations at an electrochemical sensor, typically a carbon-fiber microelectrode. WINCS comprises a battery-powered patient module and a custom software application (WINCSware) running on a nearby personal computer. The patient module impresses upon the electrochemical sensor either a constant potential (for FPA) or a time-varying waveform (for FSCV). A transimpedance amplifier converts the resulting current to a signal that is digitized and transmitted to the base station via a Bluetooth® radio link. WINCSware controls the operational parameters for FPA or FSCV, and records the transmitted data stream. Filtered data is displayed in various formats, including a background-subtracted plot of sequential FSCV scans - a representation that enables users to distinguish the signatures of various analytes with considerable specificity. Dopamine, glutamate, adenosine and serotonin were selected as analytes for test trials. Proof-of-principle tests included in vitro flow-injection measurements and in vivo measurements in rat and pig. Further testing demonstrated basic functionality in a 3-Tesla MRI unit. WINCS was designed in compliance with consensus standards for medical electrical device safety, and it is anticipated that its capability for real-time intraoperative monitoring of neurotransmitter release at an implanted sensor will prove useful for advancing functional neurosurgery