NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents.

Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses. Other RFamide peptides, including neuropeptide AF, neuropeptide SF and RFamide related peptide also target NPFFR1 or NPFFR2, and have been reported to activate the HPA axis and induce anxiety- or depression-like behaviors. However, little is known about the action of NPFF on HPA axis activity and anxiety-like behaviors, and the role of the individual receptors remains unclear. In this study, NPFFR2 agonists were used to examine the role of NPFFR2 in activating the HPA axis in rodents. Administration of NPFFR2 agonists, dNPA (intracerebroventricular, ICV) and AC-263093 (intraperitoneal, IP), time-dependently (in rats) and dose-dependently (in mice) increased serum corticosteroid levels and the effects were counteracted by the NPFF receptor antagonist, RF9 (ICV), as well as corticotropin-releasing factor (CRF) antagonist, α-helical CRF(9-41) (intravenous, IV). Treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings reveal, for the first time, that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors.

Pictionary-based fMRI paradigm to study the neural correlates of spontaneous improvisation and figural creativity.

A novel game-like and creativity-conducive fMRI paradigm is developed to assess the neural correlates of spontaneous improvisation and figural creativity in healthy adults. Participants were engaged in the word-guessing game of Pictionary(TM), using an MR-safe drawing tablet and no explicit instructions to be "creative". Using the primary contrast of drawing a given word versus drawing a control word (zigzag), we observed increased engagement of cerebellum, thalamus, left parietal cortex, right superior frontal, left prefrontal and paracingulate/cingulate regions, such that activation in the cingulate and left prefrontal cortices negatively influenced task performance. Further, using parametric fMRI analysis, increasing subjective difficulty ratings for drawing the word engaged higher activations in the left pre-frontal cortices, whereas higher expert-rated creative content in the drawings was associated with increased engagement of bilateral cerebellum. Altogether, our data suggest that cerebral-cerebellar interaction underlying implicit processing of mental representations has a facilitative effect on spontaneous improvisation and figural creativity.

Rapid detection of copper chlorophyll in vegetable oils based on surface-enhanced Raman spectroscopy.

The addition of copper chlorophyll and its derivatives (Cu-Chl) to vegetable oils to disguise them as more expensive oils, such as virgin olive oils, would not only create public confusion, but also disturb the olive oil market. Given that existing detection methods of Ch-Chl in oils, such as LC-MS are costly and time consuming, it is imperative to develop economical and fast analytical techniques to provide information quickly. This paper demonstrates a rapid analytical method based on surface-enhanced Raman spectroscopy (SERS) to detect Cu-Chl in vegetable oils; the spectroscopic markers of Cu-Chl are presented and a detection limit of 5 mg kg(-1) is demonstrated. The analysis of a series of commercial vegetable oils is undertaken with this method and the results verified by a government agency. This study shows that a SERS-based assessment method holds high potential for quickly pinpointing the addition of minute amounts of Cu-Chl in vegetable oils.

Single-Incision laparoscopic surgery (SILS) for ventriculoperitoneal shunt placement.

BACKGROUND: Single-incision laparoscopic surgery (SILS) may facilitate safer shunt placement and lower distal obstruction rate than is seen in conventional surgery. OBJECTIVE: We reviewed our 2-year experience in SILS for ventriculoperitoneal shunt placement to evaluate its usefulness and safety.Materials and Methods In this retrospective study, we enrolled patients older than 18 years with dilated ventricle and syndromes of hydrocephalus. A total of 31 patients underwent 31 primary ventriculoperitoneal shunt placement surgery and two underwent revision surgery. All the procedures were performed by the SILS technique. RESULTS: The entire duration of ventriculoperitoneal shunt implantation ranged from 45 to 80 minutes, with mean operation time of 65 ± 15.3 minutes. No major laparoscopy-related complications were noted. Shunt infection, peritonitis, and distal catheter malfunction occurred in one case (3.2%), proximal malfunction in one case (3.2%), and subcutaneous emphysema occurred in two cases (6.4%). The emphysema resolved within 2 days. Cosmetic results were "very good to good" in 17 patients (54.8%) and "satisfactory" in 14 patients (45.2%). The abdominal scars in most cases were nearly invisible. CONCLUSION: SILS is a safe and effective technique for ventriculoperitoneal shunt placement and can be accomplished with no higher risk of shunt infection and distal malfunction. Without an additional port, SILS allows good visualization of the peritoneal cavity to avoid major intra-abdominal complications. Only one 6-mm incision at the umbilicus area is required and is almost invisible after wound healing.

Robotic skull base surgery via supraorbital keyhole approach: a cadaveric study.

BACKGROUND: The supraorbital keyhole approach has been used in anterior skull base tumor and aneurysm surgery. However, there are debates regarding the safety and limitations of this kind of approach. OBJECTIVE: To determine the feasibility and potential benefits of surgical robotic technology in minimally invasive neurosurgery. METHODS: Two fresh cadaver heads were studied with the da Vinci Surgical System with 0° and 30° stereoscopic endoscopes to visualize neuroanatomy. The ability of the system to suture and place clips under the keyhole approach was tested. RESULTS: The da Vinci Surgical System was used throughout the supraorbital transeyebrow keyhole approach. With the use of standard microdissection techniques, the optic nerve, optic chiasm, carotid artery, and third cranial nerve were visualized. The sylvian fissure was then exposed from the proximal sylvian membrane to the distal M1 segment. With the EndoWrist microforceps, suturing can be achieved smoothly to close a defect created on the M2 artery. Although the benefits in adjusting clips during aneurysm surgery could be provided by an articulating applier, a proper robotic applier is not currently available. CONCLUSION: The minimally invasive supraorbital keyhole surgery can be achieved with the da Vinci Surgical System in cadaver models. This system provides neurosurgeons with broader vision and articulable instruments, which standard microsurgical systems do not provide. Further studies are necessary to evaluate the safety and benefits of using the da Vinci Surgical System in minimally invasive neurosurgery.

Pituitary stalk Langerhans cell histiocytosis treated with CyberKnife radiosurgery.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare idiopathic disease that is characterized by clonal proliferation of Langerhans histiocytes in various parts of the body. These atypical cells have been found to infiltrate single or multiple organs, including bone, lungs, liver, spleen, lymph nodes, and skin. Central nervous system invasion in LCH patients has rarely been reported, especially in the adult population. METHODS AND RESULTS: We describe three histopathologically confirmed cases of adult LCH that involves both the pituitary stalk and hypothalamus, and report our limited experience of such cases in this location that has been treated with CyberKnife radio surgery. CONCLUSION: The treatment goal of controlling lesion growth is achieved by CyberKnife radiosurgery in this case series. All patients tolerated the treatment well without obvious complications.

Sarcoma of the cervical spine after radiation treatment for thyroid cancer.

STUDY DESIGN: Case report. OBJECTIVE: We report a rare case of postradiation sarcoma of the cervical spine 30 years after treatment for thyroid cancer. SUMMARY OF BACKGROUND DATA: The reported case is a 66-year-old man with a history of thyroid cancer treated with surgery and radiotherapy at the age of 36 years. He was disease-free for 30 years, but then developed left upper limb weakness and numbness. Magnetic resonance imaging showed a homogeneously enhanced mass lesion with cystic parts involving the C4 vertebral body and occupying the left side of the spinal canal with extension to the paraspinal space through the neural foramen. METHODS: Using staged posterior and anterior approaches, gross total tumor excision, C4 corpectomy, and spinal fusion were achieved. RESULTS: The histologic diagnosis revealed sarcoma that was immunoreactive to vimentin and focally to S100 and O13 antibodies. Radiation-induced sarcoma should be suspected in patients who have received radiation treatment previously and present with new neurologic symptoms and signs in the irradiated area. The patient's muscle power returned to 5/5, except for the left upper extremity, which reached 2/5; he was free from recurring symptoms during the follow-up period. CONCLUSION: Because of advancements in diagnostic techniques and therapeutic methods, more patients survive primary cancer, and therefore an increase in the number of cases of postradiation sarcoma is expected. Postradiation sarcomas have extremely long latent periods, and one should therefore always keep in mind such a complication of previous radiation treatment.

Decompressive craniectomy as the primary surgical intervention for hemorrhagic contusion.

The standard surgical treatment of hemorrhagic cerebral contusion is craniotomy with evacuation of the focal lesion. We assessed the safety and feasibility of performing decompressive craniectomy and duraplasty as the primary surgical intervention in this group of patients. Fifty-four consecutive patients with Glasgow Coma Scale (GCS) scores of less than or equal to 8, a frontal or temporal hemorrhagic contusion greater than 20 cm(3) in volume, and a midline shift of at least 5 mm or cisternal compression on computer tomography (CT) scan were studied. Sixteen (29.7%) underwent traditional craniotomy with hematoma evacuation, and 38 (70.4%) underwent craniectomy as the primary surgical treatment. Mortality, reoperation rate, Glasgow Outcome Scale-Extended (GOSE) scores, and length of stay in both the acute care and rehabilitation phase were compared between these two groups. Mortality (13.2% vs. 25.0%) and reoperation rate (7.9% vs. 37.5%) were lower in the craniectomy group, whereas the length of stay in both the acute care setting and the rehabilitation phase were similar between these two groups. The craniectomy group also had better GOSE score (5.55 vs. 3.56) at 6 months. Decompressive craniectomy is safe and effective as the primary surgical intervention for treatment of hemorrhagic contusion. This study also suggests that patient with hemorrhagic contusion can possibly have better outcome after craniectomy than other subgroup of patients with severe traumatic brain injury.

Clinical outcome of severe head injury in different protocol-driven therapies.

In the past 5 years cerebral perfusion pressure (CPP) management has become mainstream in the treatment of severe head injuries. The American Association of Neurological Surgeons guidelines (2000) suggest that CPP should be maintained at least 70 mmHg; however, there is still debate about optimal CPP level. The purpose of this study is to evaluate the effectiveness of three widely used therapies: intracranial pressure (ICP)-targeted therapy, CPP-targeted therapy with CPP > 70 mmHg, and modified CPP-targeted therapy with CPP > 60 mmHg. The clinical procedures, complications, and patient outcomes are compared. Data including patient age, sex, initial Glasgow Coma Score (GCS), ICP, CPP, fluid status, amount of mannitol and vasopressor used, daily intake and output, complications, and clinical results were collected from 213 patients with severe head injuries over a 12-year period. Patients were categorized into three groups (ICP, CPP, modified CPP [mCPP]) according to treatment protocol used. Retrospective data collection was by chart review. The mortality rate was 28.6%, 14.3%, and 13.5% in groups ICP, CPP, and mCPP, respectively. Highest intake/output ratio, amount of vasopressor used, and pulmonary complication rates were seen in group CPP patients. Group mCPP patients showed the best clinical outcome and lowest complication rate. Though CPP-targeted therapy is the most recommended therapeutic protocol, our data showed that the outcome is as good in the mCPP-targeted group with CPP > 60 mmHg as in the CPP-targeted group, but complications are fewer in the mCPP group.

Clinical experience of hydroxyethyl starch (10% HES 200/0.5) in cerebral perfusion pressure protocol for severe head injury.

BACKGROUND: The present study was undertaken to evaluate 10% hydroxyethyl starch (HES 200/0.5) with regard to its clinical outcome and safety in the treatment of severe head injury. METHODS: Retrospective review of patient data from a prospectively designed standard treatment protocol for severe head injury. The standard protocol included (1) cerebral perfusion pressure higher than 60 mm Hg, (2) colloid solution (10% HES 200/0.5) 1000 mL/d in combination with crystalloid solution, (3) stepwise management of intracranial hypertension. Renal function, coagulation function, and electrolytes were evaluated every other day. The data of intracranial pressure, mean arterial pressure, cerebral perfusion pressure, intake, output, mannitol, complications, and outcome were recorded and analyzed. RESULTS: There were 78 patients, aged 45.61 +/- 21.80 years, in this study. The initial Glasgow Coma Scale score was 6.35 +/- 1.38. Seventy-three patients received operations with intracranial pressure monitoring. Blood transfusion was surgery related (days 1 and 2); otherwise, it was rarely used (P<.05). Prolonged prothrombin time was shown only 7 (2.65%) times of 234 of blood sampling. There was no anaphylactic reaction, pulmonary complications, or renal function deterioration in the course of our observation. The chart review of the patients at 6 months revealed the following: favorable outcome, 55.1%; unfavorable outcome, 33.3%; and mortality, 11.6%. CONCLUSIONS: The 10% HES (200/0.5) can be used in the treatment protocol of severe head injury. There is no definite bleeding complications documented by current dosage of HES. Besides, balanced fluid management can be achieved without causing serious pulmonary complications. However, a further randomized, prospective study is needed to define the actual benefit of HES in fluid management and clinical outcome.

Subdural intracranial pressure monitoring in severe head injury: clinical experience with the Codman MicroSensor.

BACKGROUND: Our main objective was to study the clinical outcome and complications of the subdural ICP monitoring with the CMS (Johnson and Johnson Medical Ltd, Raynhan, MA) in severe head injury. METHODS: A retrospective analysis of patients with head injury with a GCS score of 8 or less was performed. Patients with severe systemic injury with hypotension (systolic blood pressure of <90 mm Hg on admission), a GCS score of 3 with fixed and dilated pupils after resuscitation, a GCS score of 3 to 4 whose family refused aggressive treatment, and those who were dead on arrival were excluded from this study. During the period from January 1997 to April 2004, 120 patients with severe head injuries were included and met criteria for insertion of a subdural ICP monitoring device (CMS). RESULTS: A total of 120 patients (84 males and 36 females), aged 16 to 80 years old (mean, 43.8 +/- 14.4), were enrolled in the study. The average duration of ICP monitoring device use was 7.6 +/- 0.4 days (range, 2-14 days). The overall clinical outcomes of these patients were as follows: mortality rate, 13.5%; percentage of unfavorable outcomes, 17.3%; percentage of favorable outcomes, 69.2%. There were no complications such as CNS infection or hemorrhage in this study. CONCLUSION: A subdural transducer-tipped catheter (CMS) can be used as the first-line equipment for monitoring ICP in patients with severe head injury. The clinical results are similar with other recent studies, but no complication such as infection or hemorrhage occurred in this study.

Clinical outcome of severe head injury using three different ICP and CPP protocol-driven therapies.

In the past 5 years, cerebral perfusion pressure (CPP) management has become the standard in the treatment of severe head injuries. Guidelines published in 2000 suggest that CPP should be at least 70 mmHg; however, there is still debate about the optimal CPP. The purpose of the present study was to evaluate the effectiveness of these three widely used therapies: (i) intracranial pressure (ICP) targeted; (ii) CPP-targeted with CPP >70 mmHg; and (iii) modified CPP-targeted (mCPP) therapy with CPP >60 mmHg. The clinical procedures, complications and outcomes of patients in the different groups were compared. Data, including patient age, sex, initial Glasgow Coma Scale, ICP, CPP, fluid status, amount of mannitol and vasopressor used, daily fluid intake and output, complications and clinical results, were collected from 213 patients with severe head injuries over a 12-year period. Patients were categorized into three groups (ICP, CPP, mCPP) according to the treatment protocol used. Retrospective data collection was performed by chart review. The mortality rate was 28.6%, 14.3% and 13.5% in the ICP, CPP, and mCPP groups, respectively. Highest intake/output ratio, amount of vasopressor used and pulmonary complications were seen in the CPP patients. The mCPP patients showed the best clinical outcome and lowest complication rate. Although CPP-targeted therapy is the most recommended therapeutic protocol, our data show that patients treated with modified CPP-target therapy with CPP >60 mmHg have better clinical outcomes and fewer complications.