Neurodevelopmental testing of mice in the neonatal period does not affect their locomotor activity, depressive- and anxiety-like behaviour in adolescence.

Neonatal life is a sensitive period of brain plasticity. There are concerns that pre-weaning handling may therefore alter behavioural phenotype in adolescence or adulthood. Since neurodevelopment tests require daily manipulation with pups, later behavioural outcomes might be biased by repeated handling during suckling period. The aim of our study was to assess whether daily neurodevelopmental testing would cause alterations in behavioural phenotype. Sixty-four CD1 mice were randomized to tested and not tested group. In the tested group, maturation of physical features and neurodevelopment were monitored daily from postnatal day 1-21 between 9 and 11 AM. After weaning, battery of behavioural tests to monitor anxiety-like, depressive, or repetitive behaviour was performed in all mice. We revealed no significant between-group differences in performance of these tests. Our data did not confirm the assumption that early neurodevelopment testing during suckling period affects behavioural phenotype in adolescence.

The use, misuse and abuse of paraneoplastic panels in neurological disorders. A retrospective study.

OBJECTIVES: The field of paraneoplastic neurological syndromes PNS has grown exponentially with the increased identification of associated antibodies. Testing for these antibodies is commonly done in "panels" to increase sensitivity, and these panels have become a routine test on CSF samples obtained for a variety of clinical indications. Excessive testing has raised concerns about the correct utilization of these panels. Our study investigates the appropriateness of use of paraneoplastic panel in an academic, tertiary-care medical center. PATIENTS AND METHODS: We retrospectively reviewed charts of all patients who had autoimmune paraneoplastic panel testing in one year period. We collected date on demographics, clinical presentations and ancillary testings on all reviewed charts. Then, we devised an algorithm based on available data to define cases where testing had been unnecessary or likely unnecessary. RESULTS: We collected 60 cases that had undergone autoimmune paraneoplastic testing serum and/or CSF. Testing was unnecessary in 10 cases (16%), in which presentations had a definitive confirmatory tests. Testing was unlikely necessary in 11 cases (18%), in which all ancillary testing was normal in 6 cases, and presentation was not compatible with any known syndrome in 5 cases. Collectively, paraneoplastic panel testing was of extremely low yield on more than one third of the cases where where w testing was done. CONCLUSION: Our results adds to the growing concerns about the utilization of paraneoplastic panels, and the urgent need for enhanced screening and establishing a framework that can guide neurologists on when testing can have a sufficient yield to warrant it. Such framework should be built using diagnostic algorithms based on risk, clinical manifestations, characterization of autoantibodies and their associations.

Effect of needle diameter, type and volume of contrast agent on intervertebral disc degeneration in rats with discography.

PURPOSE: Discography can increase disc degeneration, but the influence of different discography variables on the degeneration of discs has not been reported. The aim of this study was to investigate the effects of discography variables of needle diameter, type of contrast agent and volume of contrast agent on disc degeneration. METHODS: Three separate experiments examined needle diameter, and type and volume of contrast agent. Coccygeal discs (Co7-10) adult male rats were used. X-rays were used to detect the disc height degeneration index at 1, 2 and 4 weeks after the procedure. MRI was used to study the changes in the disc structure and the signal intensity of IVD 2 and 4 weeks after the procedure. Disc water content and histology were measured at 4 weeks after the procedure. RESULTS: A 21-g needle significantly increased disc degeneration when compared with the 30-g needle as detected by X-ray, MRI, disc water content and histology (P < 0.05). Two microlitres of iodine significantly decreased the disc MRI signal and water content at 4 weeks compared with the same volume of normal saline (P < 0.05). Three microlitres of iodine significantly increased disc degeneration when compared with 2 µl iodine, as detected by X-ray, MRI, disc water content and histology at 4 weeks (P < 0.05). CONCLUSION: To reduce disc degeneration after discography, it may be best to choose a smaller needle size, minimize the use of contrast agent and use non-ionic contrast agents with osmotic pressure similar to the intervertebral disc. These slides can be retrieved under Electronic Supplementary Material.

From Healthcare to Warfare and Reverse: How Should We Regulate Dual-Use Neurotechnology?

Recent advances in military-funded neurotechnology and novel opportunities for misusing neurodevices show that the problem of dual use is inherent to neuroscience. This paper discusses how the neuroscience community should respond to these dilemmas and delineates a neuroscience-specific biosecurity framework. This neurosecurity framework involves calibrated regulation, (neuro)ethical guidelines, and awareness-raising activities within the scientific community.

Brain Monitoring in Critically Neurologically Impaired Patients.

Assessment of neurologic injury and the evolution of severe neurologic injury is limited in comatose or critically ill patients that lack a reliable neurologic examination. For common yet severe pathologies such as the comatose state after cardiac arrest, aneurysmal subarachnoid hemorrhage (aSAH), and severe traumatic brain injury (TBI), critical medical decisions are made on the basis of the neurologic injury. Decisions regarding active intensive care management, need for neurosurgical intervention, and withdrawal of care, depend on a reliable, high-quality assessment of the true state of neurologic injury, and have traditionally relied on limited assessments such as intracranial pressure monitoring and electroencephalogram. However, even within TBI there exists a spectrum of disease that is likely not captured by such limited monitoring and thus a more directed effort towards obtaining a more robust biophysical signature of the individual patient must be undertaken. In this review, multimodal monitoring including the most promising serum markers of neuronal injury, cerebral microdialysis, brain tissue oxygenation, and pressure reactivity index to access brain microenvironment will be discussed with their utility among specific pathologies that may help determine a more complete picture of the neurologic injury state for active intensive care management and long-term outcomes. Goal-directed therapy guided by a multi-modality approach appears to be superior to standard intracranial pressure (ICP) guided therapy and should be explored further across multiple pathologies. Future directions including the application of optogenetics to evaluate brain injury and recovery and even as an adjunct monitoring modality will also be discussed.

Evaluation of 126 Consecutive Stereotactic Procedures: Brain Biopsy, Diagnostic Yield, Accuracy, Non-Diagnostic Results, Complications and Follow-up.

AIM: A retrospective analysis of 126 consecutive computed tomography (CT)-guided, frame-based stereotactic procedures in 121 patients is presented to evaluate the diagnostic yield, accuracy, complications, management of non-diagnostic cases and followup. MATERIAL AND METHODS: The medical records of the identified patients were investigated retrospectively. Age, sex, surgical procedures, histopathological diagnosis, diagnostic yield, accuracy, complications, management of non-diagnostic cases and follow-up were analyzed in 121 consecutive patients. Stereotactic procedures were performed by the author by using Leksell's stereotactic system, and stereotactic biopsies were conducted under local anesthesia except for those patients who were not able to tolerate this treatment. These patients had control CT scans two hours after the operation. RESULTS: Patient age ranged from 2 to 82 years (mean 48 years). Stereotactic biopsy was performed in 112 patients. Cyst and abscess aspiration, intracystic catheter replacement and tumor resection with stereotactic craniotomy were among the other procedures. The diagnostic yield was 93%, and the histological accuracy was 63% with no mortality. Craniotomy and hematoma evacuation were required in two cases. The patients were followed up from one month to 17 years. CONCLUSION: Frame-based stereotactic biopsy is a safe and efficacious method with acceptable complications. Experience is important, but not sufficient for preventing complications and performing procedures accurately. Necrosis and gliosis are the most common non-diagnostic findings. Empirical treatment with presumptive diagnoses based on clinical and radiological findings and close clinical follow-up may not affect patients adversely. The follow-up of patients through examination and imaging is important to allow the revision of treatment when necessary.

Data-driven model comparing the effects of glial scarring and interface interactions on chronic neural recordings in non-human primates.

OBJECTIVE: We characterized electrode stability over twelve weeks of impedance and neural recording data from four chronically-implanted Utah arrays in two rhesus macaques, and investigated the effects of glial scarring and interface interactions at the electrode recording site on signal quality using a computational model. APPROACH: A finite-element model of a Utah array microelectrode in neural tissue was coupled with a multi-compartmental model of a neuron to quantify the effects of encapsulation thickness, encapsulation resistivity, and interface resistivity on electrode impedance and waveform amplitude. The coupled model was then reconciled with the in vivo data. Histology was obtained seventeen weeks post-implantation to measure gliosis. MAIN RESULTS: From week 1-3, mean impedance and amplitude increased at rates of 115.8 kΩ/week and 23.1 µV/week, respectively. This initial ramp up in impedance and amplitude was observed across all arrays, and is consistent with biofouling (increasing interface resistivity) and edema clearing (increasing tissue resistivity), respectively, in the model. Beyond week 3, the trends leveled out. Histology showed that thin scars formed around the electrodes. In the model, scarring could not match the in vivo data. However, a thin interface layer at the electrode tip could. Despite having a large effect on impedance, interface resistivity did not have a noticeable effect on amplitude. SIGNIFICANCE: This study suggests that scarring does not cause an electrical problem with regard to signal quality since it does not appear to be the main contributor to increasing impedance or significantly affect amplitude unless it displaces neurons. This, in turn, suggests that neural signals can be obtained reliably despite scarring as long as the recording site has sufficiently low impedance after accumulating a thin layer of biofouling. Therefore, advancements in microelectrode technology may be expedited by focusing on improvements to the recording site-tissue interface rather than elimination of the glial scar.

One center's experience with complications during the Wada test.

This study aimed to define the number and type of complications associated with the Wada test at an academic medical center for comparison to previous reports. We performed a retrospective review of medical records for patients who underwent the Wada test at the University of Michigan between April 1991 and June 2013. Information was collected regarding the angiography procedure and the immediate postoperative period to assess for both clinical and angiographic complications. A total of 436 patients were identified who underwent the Wada procedure between April 1991 and June 2013, and 431 patients were included in the final analysis. Twenty-five patients (5.8%) had notable clinical events associated with the Wada test. Nine patients (2.1%) had clinical events meeting criteria for complication, which included seizures, status epilepticus, internal carotid artery vasospasm, inadvertent injection of anesthetic in the external carotid artery, and transient encephalopathy. No complications were associated with significant morbidity or mortality. This retrospective review of patients undergoing the Wada test found significantly fewer associated complications in comparison to previously published studies, with no patients experiencing long-term morbidity. The Wada test should be considered a safe diagnostic tool for lateralizing language and memory.

In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes.

AIMS: To investigate whether small nerve fibre degeneration detected using corneal confocal microscopy is associated with cardiac autonomic neuropathy in people with Type 1 diabetes. METHODS: Thirty-six people with Type 1 diabetes and 20 age- and sex-matched healthy control subjects were enrolled. Tests to determine heart rate response to deep-breathing (expiratory-to-inspiratory ratio), heart rate response to lying-to-stand test (30:15 ratio) and blood pressure response to standing were performed to detect cardiac autonomic neuropathy. Corneal confocal microscopy was performed to assess: corneal nerve density and corneal nerve beadings; branching pattern; and nerve fibre tortuosity. RESULTS: Compared with control participants, participants with Type 1 diabetes had fewer (mean ± SD 45.4 ± 20.2 vs 92.0 ± 22.7 fibres/mm²; P < 0.001) and more tortuous corneal nerve fibres (20 participants with Type 1 diabetes vs four control participants had nerve tortuosity grade 2/3; P = 0.022) and fewer beadings (mean ± SD 15.1 ± 3.5 vs 20.6 ± 5.0; P < 0.001). Of the participants with Type 1 diabetes, 11 met the criteria for the diagnosis of cardiac autonomic neuropathy. Corneal nerve density was significantly lower in participants with cardiac autonomic neuropathy than in those without (mean ± SD 32.8 ± 16.4 vs 51.7 ± 18.9 fibres/mm²; P = 0.008). This difference remained significant after adjustment for age (P = 0.02), gender (P = 0.04), disease duration (P = 0.005), insulin requirement (P = 0.02) and neuropathy disability score (P = 0.04). CONCLUSION: This study suggests that corneal confocal microscopy could represent a new and non-invasive tool to investigate cardiac autonomic neuropathy in people with Type 1 diabetes. Larger studies are required to define the role of corneal confocal microscopy in the assessment of cardiac autonomic neuropathy.

Utility of different seizure induction protocols in psychogenic nonepileptic seizures.

Psychogenic non epileptic seizure (PNES) can be induced by several induction tests but their relative usefulness has not been evaluated. In this study, we report the sensitivity and specificity of various induction tests in the diagnosis of PNES and assess their discomfort level. The induction tests were: (a) compression of temple region (CTR), (b) verbal suggestion (VS), (c) tuning fork application (TFA), (d) moist swab application (MSA), (e) torch light stimulation (TLS) and (f) saline injection (SI). Up to 3 trials were done for each test except for normal saline injection which was given once. For comparison of these tests, patients with epileptic seizures were included as controls. The time to precipitate PNES was recorded and patients' discomfort levels were noted on a 0-10 scale. Video EEG was recorded in the PNES patients. 140 patients with PNES and 50 controls with epileptic seizures were included. The diagnostic yield of CTR was 65.7%, TFA 61.4%, MSA 60.7%, SI 55.6%, VS 54.3% and TLS 40.7%. These tests did not induce seizures in the controls. All these tests had 100% specificity and 100% positive predictive value in the diagnosis of PNES. The maximum discomfort was reported with SI and minimum with MSA. The similarity of efficacy and discomfort with CTR and TFA appear to be the most optimal induction techniques when compared with VS, AMS, TLS, and SI.

Completing the apnea test: decline in complications.

INTRODUCTION: The apnea test is a crucial component of the clinical diagnosis of brain death. Apprehension about hypoxemia, hypotension, and/or cardiac arrhythmias may sometimes lead clinicians to avoid performing or prematurely terminate the apnea test. The purpose of this study was to perform a contemporary re-evaluation of the safety of the apnea test. METHODS: We performed a detailed chart review of consecutive brain dead patients who underwent an apnea test from 2008 to 2012. RESULTS: Out of 63 patients, 33 were men (52.4 %). Mean age was 46.4 years. In all but four patients (93.7 %), the apnea test was performed by a neurointensivist. Infiltrates on chest radiographs were present in 34 (54 %). Seven patients (11.1 %) had chest tubes, six of which were associated with polytrauma. Echocardiograms were obtained in 47 patients (74.6 %), and 18 patients (38.3 %) had regional wall motion abnormalities (IQR 41-65 %). Fifty patients (79.4 %) were on vasopressors prior to apnea test. Median FiO2 was 0.5 (IQR 0.4-0.6), and PEEP was 5 cm H2O (IQR 5-10). After apnea test, median pO2 was 306 mmHg (IQR 121-389). Apnea test was aborted in only one patient; this patient had required FiO2 0.9-1.0 prior to the test and desaturated during the test. Mild hypoxemia occurred in three others without any consequences. Mild hypotension occurred in 11 patients (17.4 %) and was easily managed by an increase in the vasopressor infusion. There were no instances of major cardiac arrhythmias. CONCLUSION: Apnea determined using the oxygenation diffusion method during brain death testing is very safe, provided appropriate prerequisites are met. We found a major decrease in the number of aborted or not attempted apnea tests compared to previous studies.

Intravenous methylprednisolone reduces the risk of propofol-induced adverse effects during Wada testing.

The adverse effects and risks associated with intracarotid propofol injection during Wada testing were retrospectively compared in two groups of patients with (n = 75) and without (n = 58) intravenous methylprednisolone administered before intracarotid propofol injection. The incidences of all adverse effects were decreased in the methylprednisolone group. In particular, severe adverse effects such as increased muscle tone with twitching and rhythmic movements or tonic posture, which could adversely affect Wada test results, were seen in one patient in the methylprednisolone group and seven patients in the control group, indicating 92% risk reduction. This study suggests that Wada testing using intravenous methylprednisolone administration prior to propofol injection is a safe approach to the preoperative evaluation of brain tumors, epilepsy, and arteriovenous malformations.

Value and pitfalls of neurophysiological monitoring in thoracic and thoracoabdominal aortic replacement and endovascular repair.

BACKGROUND: The aim of our study was to analyze the neurophysiological monitoring method with regard to its potential problems during thoracic and thoracoabdominal aortic open or endovascular repair. Furthermore, preventive strategies to the main pitfalls with this method were developed. METHODS: Between 11/2000 and 05/2007 in 97 cases open surgery or endovascular stentgraft-implantation was performed on the thoracic or thoracoabdominal aorta. Intraoperatively, neurophysiologic motor- and somatosensory-evoked potentials were monitored. RESULTS: Our cases were divided into four groups: event-free patients with normal potentials (A, 63 cases), with correlation of modified evoked potentials and neurological outcome (B, 14 cases), false-positive or false-negative results (C, 4 cases), and medication interaction or technical issues (D, 16 cases). We observed a sensitivity of 93 % and a specificity of 96 % for the neurophysiological monitoring. CONCLUSIONS: Monitoring spinal cord function during surgical and endovascular interventions on the thoracic and thoracoabdominal aorta is necessary. It can be made more effective by precisely analyzing the interference factors of the neurophysiological monitoring method itself. Successful strategies of immediate troubleshooting could be identified.

Open biopsy in patients with acute progressive neurologic decline and absence of mass lesion.

OBJECTIVE: Patients with acute to subacute neurologic decline undergo a battery of imaging and laboratory tests to determine a diagnosis and treatment plan. Often, after an extensive evaluation, a brain biopsy is recommended as yet another tool to assist in determining the diagnosis. The goal of this retrospective cohort analysis is to measure the sensitivity of open brain biopsy in this patient population, compare these results with the preoperative presumed diagnosis, and evaluate if the biopsy result significantly alters treatment. METHODS: The authors reviewed the medical records of 135 consecutive patients who underwent open brain biopsies for acute to subacute progressive neurologic decline between January 1999 and September 2008 at a single institution. All patients with mass lesions, with HIV/AIDS, and who were younger than 20 years of age were excluded from the study. Fifty-one patients met these criteria and all preoperative tests, imaging, and treatment plans were examined and compared with postbiopsy interventions to determine the impact of the biopsy on patient outcome. RESULTS: The sensitivity of open brain biopsy at our institution was 35%. The most common preoperative presumed diagnosis was vasculitis and the most common postoperative finding was Creutzfeldt-Jakob disease, followed by amyloid angiopathy. Postbiopsy hemorrhage was a complication in 4% of patients. Treatment plans changed as a direct result of the biopsy in 8% of patients, and in only 4% did the biopsy findings make a difference in disease course. CONCLUSION: In patients with progressive neurologic decline without a radiographic mass lesion or immunodeficiency, open brain biopsy often fails to provide a diagnosis and even more rarely does it significantly alter treatment.

Justified use of painful stimuli in the coma examination: a neurologic and ethical rationale.

Much has been written about the neurologic basis and rationale for the coma examination, but little has been written about its ethical framework. In contrast to the neurologic framework, the ethical basis for the use of painful stimuli in the coma examination is context dependent and value driven, aimed at identifying the ethical justification for healthcare professionals to cause pain for patients in ways that would not be tolerated or justifiable in any other setting. Basic ethical principles can be used to justify the use of painful stimuli to examine patients, but they also impose limits on their use. To clarify the ethical issues that apply to the coma examination, we review its neurologic and ethical bases and propose a practical test by which to justify the use of painful stimuli.

Diagnostic lumbar puncture: minimizing complications.

Diagnostic lumbar puncture (LP) is essential to the diagnosis of central nervous system infections and subarachnoid haemorrhage. Life or limb-threatening adverse events due to the procedure are rare, but less severe complications may be common. Clinical practice in diagnostic LP is often not evidenced based. The aim of the study was to use best available published evidence to address questions on minimizing complications associated with diagnostic LP. We searched PubMed for studies in the English language using key words relevant to the complications of diagnostic LP. We emphasized randomized controlled trials and systematic reviews enrolling adult patients undergoing diagnostic LP. Uncontrolled studies and studies involving children or spinal anaesthesia were considered when no other evidence was available. There were nine prospective studies and three systematic reviews on reducing complications from LP. Recommendations on interventions to minimize complications of LP are graded based on the quality and strength of evidence.