The management of trigeminal neuralgia with triptans, a narrative review of the literature.

OBJECTIVE: The objective of this paper is to present a narrative review of the use of triptans in the treatment of trigeminal neuralgia (TN), as well as to outline possible therapeutic mechanisms of action. BACKGROUND: TN is a debilitating neuropathic disorder with a variety of surgical and pharmacological treatments currently available. Despite treatment being heavily individually tailored, some patients remain refractory to management. The use of triptans for the treatment of TN has been commented on in the literature, yet major trials showing their effectiveness are lacking. METHODS: A narrative review of current literature was conducted to identify published original research analyzing the usage of triptans in TN via PubMed and Google Scholar. RESULTS: Limited case reports and studies have been done to analyze the use of triptans for the treatment of TN. Despite the limited results, the studies that have been done show some promise for triptans as an alternative treatment, in particular to those with refractory TN. Given the incapacitating nature of TN, another alternative treatment may be of benefit to those patients and can help reduce its associated morbidity. CONCLUSION: Patients with refractory TN may find relief of symptoms from the use of triptans. Larger clinical trials are needed to help determine which patients would benefit from their use as well as specific dosing. Caution should be given regarding the long-term use of triptans, in particular for the typical patient population with TN.

'Down to the person, the individual patient themselves': A qualitative study of treatment decision-making for shoulder pain.

INTRODUCTION: Many inconsistencies have been identified in the translation of evidence-based treatment recommendations for musculoskeletal shoulder pain into healthcare services, with little known about factors influencing decision-making. The objective of this study was to explore the views and experiences of healthcare providers (HCPs) and people living with shoulder pain on treatment decision-making. METHODS: Adopting a qualitative design, purposeful sampling was employed to recruit 13 individuals with nonspecific musculoskeletal shoulder pain and 30 HCPs. Data were collected through 1:1 semi-structured interviews and analysed using an approach informed by Constructivist Grounded Theory. To facilitate analysis, two patient and public involvement (PPI) meetings were conducted. RESULTS: Most participants (69%) had shoulder pain of ≥1-year duration. Biomechanical beliefs about shoulder pain predominated and were heavily influential in decision-making for both patients and HCPs. Despite a consensus that therapeutic alliance facilitated decision-making, the extent of collaboration between HCPs and patients in treatment decision-making was rather limited. In addition to condition-specific factors, Individual patient characteristics and resources also influenced treatment decisions. CONCLUSION: Findings revealed the complexity of the decision-making process for both patients and HCPs, exposing substantial gaps between the reported views and experiences of participants and the principles of client-centred and evidence-based practice. There is a pressing need to enhance the translation of evidence-based knowledge into practice in this clinical area. PATIENT OR PUBLIC CONTRIBUTION: In line with a consultative approach to collaborative data analysis, a subgroup of participants attended two PPI meetings to provide commentary and feedback on preliminary findings.

The Performative is Political: Using Counter-Storytelling through Theater to Create Spaces for Implicated Witnessing.

Performative counter-storytelling can be a powerful experience for both the artists who create these stories and the audiences who witness them. This study examined audience responses to a counter-narrative (entitled "AMKA") performed by Africans in Australia which intended to present more complex, holistic, and strengths-based representations of their communities than those currently circulated by dominant discourses. Guided by a critical whiteness lens, the study explored how 34 self-identifying white audience members interpreted the performance and how they questioned whiteness by assuming the role of implicated witnesses. Following thematic analysis of mixed closed- and open-ended post-performance survey responses, audience members made connections between the content of AMKA and the contemporary political and cultural contexts in which it was performed and began to examine their positions of privilege and power. This study has provided evidence for the potential of political theater in creating spaces of encounter whereby responsible listening positions can be nurtured in the journey toward dismantling personal, and potentially structural, racially-based injustices.

Case report: vertebral osteomyelitis secondary to a dental abscess.

BACKGROUND: Vertebral osteomyelitis can be attributed to many factors including immunosuppression, diabetes, malignancy, collagen disease, periodontal disease, open fractures, and endoscopic procedures. Anaerobic bacteria, such as Veillonella species, are found in the oral cavity and are rarely implicated in the infection. This report describes vertebral osteomyelitis secondary to a dental abscess with positive Veillonella cultures. CASE DESCRIPTION: A 76-year-old man presented to the hospital due to back pain with a four-day history of fever and chills. CT scans revealed several abscesses in the lumbar region as well as indications of vertebral osteomyelitis. After a psoas drain, the patient began antibiotics with a combination of ampicillin-sulbactam, metronidazole, and levofloxacin, but due to the patient's penicillin allergy, he was initially desensitized to this antibiotic for a significant period of time. Laminectomies, foraminotomies, and facetectomies were performed, but the infection spread to vertebral levels. The patient was then switched to a combination of vancomycin, metronidazole, and levofloxacin which eliminated the infection. Final laminectomy was performed with posterior segmental instrumentation and arthrodesis. Post-operatively, there were no signs of infection. The patient recovered well and regained mobility. Deeper examination of the patient's medical history revealed a severe tooth abscess immediately before the onset of bacteremia. CONCLUSION: We believe that a delay in the onset of antibiotic treatment is what led to the initial bacteremia that ultimately took root in the lower lumbar vertebrae. To the best of our ability, we could identify only one other case that linked vertebral osteomyelitis to the oral cavity.

Investigation of a Valve-Agnostic Cranial Implant for Adult Hydrocephalus Patients Requiring Ventriculoperitoneal Shunting.

INTRODUCTION: Currently, the most effective treatment strategy for adults with hydrocephalus involves cerebrospinal fluid diversion by means of a shunt system, most commonly ventriculoperitoneal shunts (VPS). Ventriculoperitoneal shunting is associated with high complication and/or revision rates, in part due to the high-profile programmable valve designs. Thus, the valve-agnostic cranial implant (VACI) was designed and investigated as a safe and effective method of reducing the valve's high profile and is currently undergoing clinical trials. As such, the objective of this study was to collate preliminary, multi-institutional data of early outcomes using a VACI approach for patients requiring VPS by way of an Institutional Review Board approved registry. METHODS: A total of 25 adult patients across 4 institutions and 6 surgeons underwent VACI placement for VPS based on preoperative evaluation and perceived benefit. Patient demographics, operative details, and preliminary outcomes are presented here. RESULTS: Valve-agnostic cranial implant placement via a limited size craniectomy at time of shunt revision was performed with no adverse events. Over an average follow-up period of 1 year (394 ±â€Š178 days), 92% of patients experienced no major shunt-related or scalp-related complications. There were 2 cases with a major complication requiring reoperation: 1 shunt tubing extrusion and 1 case of meningitis. The most frequent postsurgical intervention seen in this study was related to adjustment of drainage: a non-invasively performed valve reprogramming after initial shunt placement when proper flow rate is being established. Of the 8 cases of drainage adjustment, all but 1 (88%) were receiving a VPS for the first time, with the exception undergoing a fourth shunt revision. All instances of improper flow were treated non-surgically and remediated effectively via shunt reprogramming in clinic. Removal of the VACI was not indicated in any treatment course. In this way, all complications as they relate to the shunt valve were minor and required nonsurgical intervention, and no complications reported were directly or indirectly caused by using the VACI. CONCLUSION: Preliminary findings from this multicenter trial suggest promising outcomes with a low complication rate for patients with hydrocephalus undergoing VACI placement during VPS. Ongoing research will continue to provide a more robust clinical picture of VACI in hydrocephalus management as more data becomes available.

Region-specific disruption of the blood-brain barrier following repeated inflammatory dural stimulation in a rat model of chronic trigeminal allodynia.

Background The blood-brain barrier (BBB) has been hypothesized to play a role in migraine since the late 1970s. Despite this, limited investigation of the BBB in migraine has been conducted. We used the inflammatory soup rat model of trigeminal allodynia, which closely mimics chronic migraine, to determine the impact of repeated dural inflammatory stimulation on BBB permeability. Methods The sodium fluorescein BBB permeability assay was used in multiple brain regions (trigeminal nucleus caudalis (TNC), periaqueductal grey, frontal cortex, sub-cortex, and cortex directly below the area of dural activation) during the episodic and chronic stages of repeated inflammatory dural stimulation. Glial activation was assessed in the TNC via GFAP and OX42 immunoreactivity. Minocycline was tested for its ability to prevent BBB disruption and trigeminal sensitivity. Results No astrocyte or microglial activation was found during the episodic stage, but BBB permeability and trigeminal sensitivity were increased. Astrocyte and microglial activation, BBB permeability, and trigeminal sensitivity were increased during the chronic stage. These changes were only found in the TNC. Minocycline treatment prevented BBB permeability modulation and trigeminal sensitivity during the episodic and chronic stages. Discussion Modulation of BBB permeability occurs centrally within the TNC following repeated dural inflammatory stimulation and may play a role in migraine.

An Analysis of Transient Ischemic Attack Practices: Does Hospital Admission Improve Patient Outcomes?

INTRODUCTION: Immediate treatment has been shown to decrease the recurrence of cerebrovascular accidents following transient ischemic attacks (TIA), prompting the use of a specialized neurologic emergency department (Neuro ED) to triage patients. Despite these findings, there is little evidence supporting the notion that hospital admission improves post-TIA outcomes. Through the lens of a Neuro ED, this retrospective chart review of TIA patients examines whether hospital admission improves 90-day outcomes. MATERIALS AND METHODS: Two hundred sixty charts of patients discharged with TIA diagnosis were reviewed. These charts encompassed patients with TIA who presented to a main emergency department (ED) or Neuro ED from January 2014 to April 2015. Demographic information, admission ABCD(2) scores, admission National Institutes of Health Stroke Scale scores, and admission Modified Rankin Scale, and reason for any return visits within 90 days were collected. RESULTS: This review shows that patients triaged by the Neuro ED were admitted at a lower rate than those seen by the standard ED. Further, patients triaged by the Neuro ED experienced lower readmission and recurrence of stroke or TIA within 90 days. CONCLUSIONS: These results provide preliminary support for the notion that discharging appropriate TIA patients, with adequate follow-up, will not adversely affect the recurrence of TIA or stroke within 90 days.

Improved door-to-needle times and neurologic outcomes when IV tissue plasminogen activator is administered by emergency physicians with advanced neuroscience training.

BACKGROUND: The neurologic emergency department (neuro ED) at our medical center is staffed by emergency medicine physicians who have specialized neuroscience training and give intravenous (IV) tissue plasminogen activator (tPA) independently for acute ischemic stroke patients. Door-to-needle (DTN) times, discharge location, and discharge National Institute of Health Stroke Scale (NIHSS) scores were studied between the neuro ED and main emergency department (ED) with the hypothesis that all measures would be better in the neuro ED group. METHODS: This is a retrospective study evaluating DTN time, discharge outcomes, and discharge location in acute stroke patients who received IV tPA at our comprehensive stroke center. These outcome measures were compared between patients who were evaluated and treated in our neuro ED to those treated in our main ED. RESULTS: From 2012 to 2014, 67 acute stroke patients received IV tPA in our ED. Thirty-five patients were evaluated in the neuro ED, and 32, in the main ED. Average DTN times were significantly faster in the neuro ED at 35 minutes, compared to main ED DTN times of 83 minutes. Discharge NIHSS score was significantly lower, and more patients were discharged to home in the neuro ED group compared to the main ED group. CONCLUSIONS: Trained neuro ED physicians can safely give IV tPA independently for stroke patients with improved DTN times, lower discharge NIHSS, and higher likelihood of being discharged to home compared to the main ED physicians who used teleneurology consultation. This suggests utility in training emergency medicine physicians to administer tPA independently based on clinical practice guidelines.

A mixed-methods approach to understand victimization discourses by opposing feminist sub-groups on social media.

Opposing social movements are groups that have conflicting objectives on a shared social justice issue. To maximize the probability of their movement's success, groups can strategically portray their group in a favourable manner while discrediting their opposition. One such approach involves the construction of victimization discourses. In this research, we combined topic modelling and critical discursive psychology to explore how opposing groups within the feminist movement used victimization as a lens to understand their movements in relation to transgender women. We compiled a dataset of over 40,000 tweets from 14 UK-based feminist accounts that included transgender women as women (the pro-inclusion group) and 13 accounts, that excluded transgender women (the anti-inclusion group). Our results revealed differences in how victimization was employed by the opposing movements: pro-inclusion groups drew on repertoires that created a sense of shared victimhood between cisgender women and transgender women, while anti-inclusion groups invoked a competitive victimhood repertoire. Both groups also challenged and delegitimised their oppositions' constructions of feminism and victimhood. These findings add to our understanding of the communication strategies used by opposing movements to achieve their mobilization goals.

Multicenter comparison of Chiari malformation type I presentation in children versus adults.

OBJECTIVE: Treatment for Chiari malformation type I (CM-I) often includes surgical intervention in both pediatric and adult patients. The authors sought to investigate fundamental differences between these populations by analyzing data from pediatric and adult patients who required CM-I decompression. METHODS: To better understand the presentation and surgical outcomes of both groups of patients, retrospective data from 170 adults and 153 pediatric patients (2000-2019) at six institutions were analyzed. RESULTS: The adult CM-I patient population requiring surgical intervention had a greater proportion of female patients than the pediatric population (p < 0.0001). Radiographic findings at initial clinical presentation showed a significantly greater incidence of syringomyelia (p < 0.0001) and scoliosis (p < 0.0001) in pediatric patients compared with adult patients with CM-I. However, presenting signs and symptoms such as headaches (p < 0.0001), ocular findings (p = 0.0147), and bulbar symptoms (p = 0.0057) were more common in the adult group. After suboccipital decompression procedures, 94.4% of pediatric patients reported symptomatic relief compared with 75% of adults with CM-I (p < 0.0001). CONCLUSIONS: Here, the authors present the first retrospective evaluation comparing adult and pediatric patients who underwent CM-I decompression. Their analysis reveals that pediatric and adult patients significantly differ in terms of demographics, radiographic findings, presentation of symptoms, surgical indications, and outcomes. These findings may indicate different clinical conditions or a distinct progression of the natural history of this complex disease process within each population, which will require prospective studies to better elucidate.

Prediction of Effectiveness and Toxicities of Immune Checkpoint Inhibitors Using Real-World Patient Data.

PURPOSE: Although immune checkpoint inhibitors (ICIs) have improved outcomes in certain patients with cancer, they can also cause life-threatening immunotoxicities. Predicting immunotoxicity risks alongside response could provide a personalized risk-benefit profile, inform therapeutic decision making, and improve clinical trial cohort selection. We aimed to build a machine learning (ML) framework using routine electronic health record (EHR) data to predict hepatitis, colitis, pneumonitis, and 1-year overall survival. METHODS: Real-world EHR data of more than 2,200 patients treated with ICI through December 31, 2018, were used to develop predictive models. Using a prediction time point of ICI initiation, a 1-year prediction time window was applied to create binary labels for the four outcomes for each patient. Feature engineering involved aggregating laboratory measurements over appropriate time windows (60-365 days). Patients were randomly partitioned into training (80%) and test (20%) sets. Random forest classifiers were developed using a rigorous model development framework. RESULTS: The patient cohort had a median age of 63 years and was 61.8% male. Patients predominantly had melanoma (37.8%), lung cancer (27.3%), or genitourinary cancer (16.4%). They were treated with PD-1 (60.4%), PD-L1 (9.0%), and CTLA-4 (19.7%) ICIs. Our models demonstrate reasonably strong performance, with AUCs of 0.739, 0.729, 0.755, and 0.752 for the pneumonitis, hepatitis, colitis, and 1-year overall survival models, respectively. Each model relies on an outcome-specific feature set, though some features are shared among models. CONCLUSION: To our knowledge, this is the first ML solution that assesses individual ICI risk-benefit profiles based predominantly on routine structured EHR data. As such, use of our ML solution will not require additional data collection or documentation in the clinic.

Spontaneous trigeminal allodynia in rats: a model of primary headache.

Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.

Managing shoulder pain: a meta-ethnography exploring healthcare providers' experiences.

OBJECTIVE: To review and synthesize qualitative research studies exploring the experiences of Healthcare Providers (HCPs) of managing shoulder pain. METHODS: A meta-ethnographic approach was adopted to review and synthesize eligible studies. The findings from each included study were translated into one another using Noblit and Hares' seven-stage process. A systematic search of eleven electronic databases was conducted in February 2021. Methodological quality was assessed using the CASP Appraisal Tool. RESULTS: Ten studies were included in the meta-synthesis, all deemed of high methodological quality. Three themes were identified; (1) Lack of consensus: "we all have different approaches." (2) Challenges to Changing Practice: It's "really hard to change and switch to a different approach," (3) Getting "Buy in" to Treatment: "…so you have to really sell it early". CONCLUSION: Healthcare providers working with people with shoulder pain struggle to reconcile, often conflicting, research recommendations with their own clinical experience, beliefs and patient expectations. These findings help explain the continued lack of consensus on how best to manage shoulder pain in clinical practice.IMPLICATIONS FOR REHABILITATIONHealthcare providers (HCPs) working with people with shoulder pain struggle to resolve conflicts between evidence-based recommendations, clinical experience, their own shoulder pain beliefs and patient expectations and preferences.Stronger collaboration across professional disciplines is needed to address the current lack of consensus on the management of shoulder pain.Many HCP's find it difficult to engage patients with shoulder pain in exercise and they work hard to "sell" this approach to patients using strategies such as education, shared decision making and therapeutic alliance.

Understanding Shoulder Pain: A Qualitative Evidence Synthesis Exploring the Patient Experience.

OBJECTIVE: The objective of this study was to review and synthesize qualitative research studies exploring the experiences of individuals living with shoulder pain to enhance understanding of the experiences of these individuals as well as facilitate health care developments. METHODS: A meta-ethnographic approach was adopted to review and synthesize eligible published qualitative research studies. The findings from each included study were translated into one another using the Noblit and Hares 7-stage process. A systematic search of 11 electronic databases was conducted in March 2020. Methodological quality was assessed using the Critical Appraisal Skills Programme appraisal tool. RESULTS: Nineteen studies were included in the meta-synthesis. Included articles explored the lived experiences as well as treatment-related experiences of participants. All of the included articles were deemed to be of high methodological quality. Three themes were identified: (1) negative emotional, social, and activity impact ("It has been a big upheaval"); (2) developing an understanding ("Why is it hurting so much?"); and (3) exercise ("Am I going to go through a lot of pain in moving it…?"). Across the included studies, the severe emotional and physical impact of shoulder pain was a core finding. Many people sought a "permanent" solution involving surgery. Openness to other treatment options was influenced by factors including understanding of pain, prior experiences, and treatment expectations. CONCLUSION: These findings deepen our understanding of the impact of shoulder pain on peoples' lives and provide novel insight into the experience of treatment. Enhanced awareness of people's experiences of shoulder pain and treatment is crucial for clinicians when planning and implementing evidence-based recommendation. IMPACT: To the knowledge of the authors, this is the first qualitative evidence synthesis to explore the treatment-related experiences of individuals with shoulder pain. Shoulder surgery was considered by many as the only means to achieve a more permeant resolution of symptoms. LAY SUMMARY: Shoulder pain causes emotional and physical turmoil that can permeate every facet of life. People's understanding of their shoulder pain appears to be deeply rooted in a biomechanical view of pain, which influences their expectations relating to diagnosis and treatment.

To cut or not to cut? A case report on pediatric intervertebral disc calcification.

BACKGROUND: Intervertebral disc calcification (IVDC) is a rare cause of acute spinal pain in pediatric patients. The most common symptom is back or neck pain, but muscle spasm, muscle weakness, and sensory loss also occur. Many patients have an alarming presentation and radiological findings concerning for spinal cord compression. CASE DESCRIPTION: A 10-year-old female presented with 2 weeks of worsening back pain and restricted neck flexion with no history of preceding trauma. Magnetic resonance imaging (MRI) showed T4/5 and T5/6 vertebral disc calcification and posterior herniation causing thoracic spinal cord compression. Despite concerning imaging findings, we decided to manage this patient conservatively with nonsteroidal anti-inflammatory drugs, leading to the improvement of symptoms within 9 days, and resolution of all pain within 1 month after hospital discharge. At 6 months follow-up, MRI showed complete resolution of calcification within the spinal canal. CONCLUSION: This case report emphasizes IVDC as an important differential diagnosis of pediatric disc disease that does not require surgical intervention. X-ray imaging with PA and lateral views is an adequate screening for these patients. Majority of cases resolve within 6 months with conservative therapy.

Reversal of cognitive, behavioral, and language impairments after the left frontal arachnoid cyst fenestration in a pediatric patient.

BACKGROUND: Arachnoid cysts (ACs) are cerebrospinal fluid-containing cysts located between the surface of the brain or spinal cord and arachnoid layer of the leptomeninges. ACs have been known to cause cognitive, language, and behavioral deficits and currently there is no standard treatment paradigm. Surgical indications include papilledema, increasing growth with mass effect causing neurological deficit, or rapid head growth, however, cognitive symptoms related to mass effect may not always be considered. CASE DESCRIPTION: We present a 3-year-old male with an AC of the left anterior fossa causing frontal lobe compression with resultant behavioral, language, and cognitive deficits. CONCLUSION: Surgical intervention for AC decompression may be indicated when there are cognitive, behavioral, or language delays related to the mass effect and location of the AC. Neuropsychiatric testing or more advanced imaging studies may further support surgical treatment. After craniotomy for fenestration of the left frontal AC, there was drastic improvement in cognitive, language, and behavioral symptoms in our pediatric patient.

The Use of Antiplatelet Agents and Heparin in the 24-Hour Postintravenous Alteplase Window for Neurointervention.

BACKGROUND: Intravenous (IV) alteplase with mechanical thrombectomy has been found to be superior to alteplase alone in select patients with intracranial large vessel occlusion. Current guidelines discourage the use of antiplatelet agents or heparin for 24 h following alteplase. However, their use is often necessary in certain circumstances during thrombectomy procedures. OBJECTIVE: To study the safety and outcomes in patients who received blood thinning medications for thrombectomy after IV Tissue-Type plasminogen activator (tPA). METHODS: This is a multicenter retrospective review of the use of antiplatelet agents and/or heparin in patients within 24 h following tPA administration. Patient demographics, comorbidities, bleeding complications, and discharge outcomes were collected. RESULTS: A series of 88 patients at 9 centers received antiplatelet medications and/or heparin anticoagulation following IV alteplase for revascularization procedures requiring stenting. The mean National Institutes of Health Stroke Scale (NIHSS) on admission was 14.6. Reasons for use of a stent included internal carotid artery occlusion in 74% of patients. Thrombolysis in cerebral infarction (TICI) 2b-3 revascularization was accomplished in 90% of patients. The rate of symptomatic intracranial hemorrhage (sICH) was 8%; this was not significantly different than the sICH rate for a matched group of patients not receiving antiplatelets or heparin during the same time frame. Functional independence at 90 d (modified Rankin Scale 0-2) was seen in 57.8% of patients. All-cause mortality was 12%. CONCLUSION: The use of antiplatelet agents and heparin for stroke interventions following IV alteplase appears to be safe without significant increased risk of hemorrhagic complications in this group of patients when compared to control data and randomized controlled trials.

Ketamine modulates theta and gamma oscillations.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor glutamatergic antagonist, has been studied as a model of schizophrenia when applied in subanesthetic doses. In EEG studies, ketamine affects sensory gating and alters the oscillatory characteristics of neuronal signals in a complex manner. We investigated the effects of ketamine on in vivo recordings from the CA3 region of mouse hippocampus referenced to the ipsilateral frontal sinus using a paired-click auditory gating paradigm. One issue of particular interest was elucidating the effect of ketamine on background network activity, poststimulus evoked and induced activity. We find that ketamine attenuates the theta frequency band in both background activity and in poststimulus evoked activity. Ketamine also disrupts a late, poststimulus theta power reduction seen in control recordings. In the gamma frequency range, ketamine enhances both background and evoked power, but decreases relative induced power. These findings support a role for NMDA receptors in mediating the balance between theta and gamma responses to sensory stimuli, with possible implications for dysfunction in schizophrenia.

Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120--protection by gene delivery of antioxidant enzymes.

HIV-1 effects on the blood-brain barrier (BBB) structure and function are still poorly understood in animal models based on direct administration of recombinant HIV proteins. We therefore injected HIV-1 envelope glycoprotein, gp120, into rat caudate-putamens (CPs) and examined vascular integrity and function. Gp120 coimmunostained with endothelial cell marker, CD31. It induced apoptosis of endothelial cells in vitro and in vivo. BBB function was assessed by administering Evans Blue (EB) intravenously before injecting gp120. EB leaked near the site of gp120 administration. Within 1h after intra-CP gp120 injection, structures positive for endothelial markers ICAM-1 and RECA-1 were greatly decreased. Vascular density assessed by laminin immunostaining remained decreased 1 month after gp120 injection. RECA-1-positive cells expressed hydroxynonenal, a marker of lipid peroxidation and rSV40-mediated gene delivery of antioxidant enzymes protected the BBB from gp120-related injury. Extravasated IgG accumulated following intra-CP SV(gp120) injection, an experimental model of continuing gp120 exposure. Thus: acute and chronic exposure to gp120 disrupts the BBB; gp120-mediated BBB abnormalities are related to lesions of brain microvessels; and gp120 is directly toxic to brain endothelial cells.

The effects of spinal manipulative therapy on lower limb neurodynamic test outcomes in adults: a systematic review.

Objective: Spinal Manipulative Therapy (SMT) is a routinely applied treatment modality for various musculoskeletal conditions, including low back pain. The precise mechanisms by which SMT elicits its effects are largely unknown, but recent research supports a multi-system explanation recognizing both biomechanical and neurophysiological mechanisms. Although the evaluation of changes in clinical presentation is complex, objective neurophysiological measures of sensitivity to movement (e.g. neurodynamic tests) can be a valuable clinical indicator in evaluating the effects of SMT. This review aimed to synthesize current literature investigating the effects of SMT on lower limb neurodynamics.Method: Eight electronic databases were systematically searched for randomized controlled trials (RCT) that applied SMT (against any control) and evaluated lower limb neurodynamics (Passive Straight Leg Raise or Slump Test). Selection and data extraction were conducted by one researcher, reviewed by a second author. Risk of bias (RoB) was assessed using the Cochrane Back Review Group criteria.Results: Eight RCTs were included, one with high RoB. SMT produced a clinically meaningful (≥6°) difference in five of these studies compared with inert control, hamstring stretching, and as an adjunct to conventional physiotherapy, but not compared with standard care, as an adjunct to home exercise and advice, or when comparing different SMT techniques. Findings compared to sham were mixed. When reported, effects tentatively lasted up to 6 weeks post-intervention.Conclusion: Limited evidence suggests SMT-improved range of motion and was more effective than some other interventions. Future research, using standardized Neurodynamic tests, should explore technique types and evaluate longer-term effects.Level of Evidence: 1a.