N-Methyl-d-aspartate (NMDA) receptors play a variety of physiologic roles and their proper signaling is essential for cellular homeostasis. Any disruption in this pathway, leading to either enhanced or decreased activity, may result in the manifestation of neuropsychiatric pathologies such as schizophrenia, mood disorders, substance induced psychosis, Huntington’s disease, Alzheimer’s disease, and neuropsychiatric systemic lupus erythematosus. Here, we explore the notion that the overlap in activity of at least one biochemical pathway, the NMDA receptor pathway, may be the link to understanding the overlap in psychotic symptoms between diseases. This review intends to present a broad overview of those neuropsychiatric disorders for which alternations in NMDA receptor activity is prominent thus suggesting that continued direction of pharmaceutical intervention to this pathway may present a viable option for managing symptoms.
NMDA; psychiatry; schizophrenia; mood disorders; substance induced psychosis; Huntington’s disease; Alzheimer’s disease; neuropsychiatric systemic lupus erythematosus
Prescription stimulants are often used to treat attention deficit hyperactivity disorder (ADHD). Drugs like methylphenidate (Ritalin, Concerta), dextroamphetamine (Dexedrine), and dextroamphetamine-amphetamine (Adderall) help people with ADHD feel more focused. However, misuse of stimulants by ADHD and nonaffected individuals has dramatically increased over recent years based on students' misconceptions or simple lack of knowledge of associated risks. In this review, we discuss recent advances in the use and increasing misuse of prescription stimulants among high school and college students and athletes. Given the widespread belief that stimulants enhance performance, there are in fact only a few studies reporting the cognitive enhancing effects of stimulants in ADHD and nonaffected individuals. Student athletes should be apprised of the very serious consequences that can emerge when stimulants are used to improve sports performance. Moreover, misuse of stimulants is associated with dangers including psychosis, myocardial infarction, cardiomyopathy, and even sudden death. As ADHD medications are prescribed for long-term treatment, there is a need for long-term safety studies and education on the health risks associated with misuse is imperative.
Amphetamine; athletes; attention deficit hyperactivity disorder; cognition; methylphenidate; misuse; performance; students
Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases that mediate extracellular matrix turnover and associated processes, such as cell survival, growth, and differentiation. This paper discusses important functions of MMP in the normal and injured nervous system, focusing on the role played by these proteases in neurological pain syndromes, most prominently in neuropathic pain and migraine headaches. In the past decade, metalloproteinases emerged as key modulators of neuropathic pain, with MMP-9 acting as an initiator of the neuropathic cascade. Increased MMP activity was detected in migraine patients, independent of aura, in tight association with metabolic derangements. The therapeutic implications of MMP inhibition are considered in the context of neurogenic pain regulation.
Background. Stroke occurs due to an interruption in cerebral blood supply affecting neuronal function. Body temperature on hospital admission is an important predictor of clinical outcome. Therapeutic hypothermia is promising in clinical settings for stroke neuroprotection. Methods. MEDLINE/PubMed, CENTRAL, Stroke Center, and ClinicalTrials.gov were systematically searched for hypothermia intervention induced by external or endovascular cooling for acute stroke. NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were the main stroke scales used, and mortality was also reported. A meta-analysis was carried out on stroke severity and mortality. Results. Seven parallel-controlled clinical trials were included in the meta-analysis. Sample sizes ranged from 18 to 62 patients, yielding a total of 288. Target temperature (∼33°C) was reached within 3-4 hours. Stroke severity (Cohen's d = −0.17, 95% CI: −0.42 to 0.08, P = 0.32; I2 = 73%; Chi2 = 21.89, P = 0.0001) and mortality (RR = 1.60, 95% CI: 0.93 to 2.78, P = 0.11; I2 = 0%; Chi2 = 2.88, P = 0.72) were not significantly affected by hypothermia. Discussion. Hypothermia does not significantly improve stroke severity; however, this finding should be taken with caution due to the high heterogeneity and limited number of included studies. No impact on mortality was observed.
Mindfulness-based therapy (MBT) has been used effectively to treat a variety of physical and psychological disorders, including depression, anxiety, and chronic pain. Recently, several lines of research have explored the potential for mindfulness-therapy in treating somatization disorders, including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome.
Thirteen studies were identified as fulfilling the present criteria of employing randomized controlled trials to determine the efficacy of any form of MBT in treating somatization disorders. A meta-analysis of the effects of mindfulness-based therapy on pain, symptom severity, quality of life, depression, and anxiety was performed to determine the potential of this form of treatment.
While limited in power, the meta-analysis indicated a small to moderate positive effect of MBT (compared to wait-list or support group controls) in reducing pain (SMD = −0.21, 95% CI: −0.37, −0.03; p<0.05), symptom severity (SMD = −0.40, 95% CI: −0.54, −0.26; p<0.001), depression (SMD = −0.23, 95% CI: −0.40, −0.07, p<0.01), and anxiety (SMD = −0.20, 95% CI: −0.42, 0.02, p = 0.07) associated with somatization disorders, and improving quality of life (SMD = 0.39, 95% CI: 0.19, 0.59; p<0.001) in patients with this disorder. Subgroup analyses indicated that the efficacy of MBT was most consistent for irritable bowel syndrome (p<0.001 for pain, symptom severity, and quality of life), and that mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MCBT) were more effective than eclectic/unspecified MBT.
Preliminary evidence suggests that MBT may be effective in treating at least some aspects of somatization disorders. Further research is warranted.
The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer’s disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet.
Obesity; Nutrition; Cognition; Fructose; Diabetes; Dementia; Omega-3 fatty acids
Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1), a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs’ role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined.
matrix metalloproteinases; blood-brain barrier; stroke; caveolin-1; reactive oxygen species
Current antidepressants used to treat pediatric patients have the disadvantage of limited efficacy and potentially serious side effects. The purpose of this study was to assess the efficacy of vitamin C as an adjuvant agent in the treatment of pediatric major depressive disorder in a six-month, double-blind, placebo-controlled pilot trial.
The study group (n=12) was given fluoxetine (10–20 mg/day) plus vitamin C (1000 mg/day) and control group (n=12) administered fluoxetine (10–20 mg/day) plus placebo. The data were analyzed by ANOVA and t-test for independent samples.
Both groups demonstrated significantly improved scores on the Children’s Depression Rating Scale (CDRS), the Children’s Depression Inventory (CDI), and the Clinical Global Impression (CGI). ANOVA was significantly different on all clinical measurements (group effect, time effect, and interaction), with the exception of group effect and interaction for CGI. Patients treated for six months with fluoxetine and vitamin C showed a significant decrease in depressive symptoms in comparison to the fluoxetine plus placebo group as measured by the CDRS (t=11.36, P<0.0001) and CDI (t=12.27, P<0.0001), but not CGI (t=0.13, P=0.90). No serious adverse effects were observed.
These preliminary results suggest that vitamin C may be an effective adjuvant agent in the treatment of MDD in pediatric patients.
Microsatellites are nucleotide sequences of tandem repeats occurring throughout the genome, which have been widely used in genetic linkage analysis, studies of loss of heterozygosity, determination of lineage and clonality, and the measurement of genome instability or the emergence of drug resistance reflective of mismatch repair deficiency. Such analyses may involve the parallel evaluation of many microsatellite loci, which are often limited by sample DNA, are labor intensive, and require large data processing.
To overcome these challenges, we developed a cost-effective high-throughput approach of microsatellite analysis, in which the amplifications of microsatellites are performed in miniaturized, multiplexed polymerase chain reaction (PCR) adaptable to 96 or 384 well plates, and accurate automated allele identification has been optimized with a collective reference dataset of 5,508 alleles using the GeneMapper software.
In this investigation, we have documented our experience with the optimization of multiplex PCR conditions and automated allele identification, and have generated a unique body of data that provide a starting point for a cost-effective, high-throughput process of microsatellite analysis using the studied markers.
Microsatellite instability; Loss of heterozygosity; Multiplexed PCR
Acute cerebral edema is a significant cause of death in patients treated for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome.
We present the case of a 44-year-old African American woman admitted with acute severe headache and diagnosed with diabetic hyperglycemic hyperosmolar syndrome. Computed tomography of the head showed diffuse leukoencephalopathy, but sparing of the cortex. We were concerned for acute cerebral edema secondary to hyperglycemic hyperosmolar syndrome. Magnetic resonance imaging of the brain showed numerous collections of cystic spaces in the white matter of both hemispheres representing tumefactive perivascular spaces. Her headache improved with correction of the hyperglycemic hyperosmolar state.
Although the clinical presentation and head computed tomography were concerning for cerebral edema, the distinctive features on brain magnetic resonance imaging helped to clarify the diagnosis and differentiate it from other processes.
Tumefactive perivascular spaces; Cerebral edema; Hyperglycemic hyperosmolar syndrome
MRI is considered a safe and well tolerated imaging technique with risks largely limited to heating and/or displacement of implanted ferromagnetic metal in the patient’s body, worsening anxiety, triggering claustrophobia, and gadolinium induced nephrogenic systemic fibrosis.
We present a case of a 26 year old Asian American man with no significant past medical or psychiatric history and two months of left T4 radicular pain. During 3T-MRI of the whole spine, the patient experienced acute agitation, fear, anxiety, tachypnea, tachycardia with palpitations, and dizziness. He felt intense surface heat over segments of his body and very loud noises. He perceived impending serious bodily harm by the scanner. The scan was aborted at the lumbar spine, and cervical and thoracic spine was unremarkable. The patient’s pain resolved in the weeks following with over the counter analgesics, however, he developed increased arousal, re-experiencing the event, persistent avoidance, and significant psychosocial impairment consistent with DSM-IV-TR criteria for post-traumatic stress disorder (PTSD).
This is the first reported case of MRI induced PTSD. Theoretically, the high-magnetic field of the 3T scanner may have contributed to the development of symptoms.
PTSD; MRI; Imaging; Anxiety; Stress
Schizophrenia and bipolar disorder are the two most serious and debilitating neuropsychiatric disorders that share many characteristics, both symptomatic and epidemiological. There has yet to be a single diagnostic biomarker discovered for schizophrenia and bipolar disorder. Proteomics holds promise in elucidating the pathophysiology of these neuropsychiatric disorders from each other and healthy individuals.
Postmortem prefrontal cortex tissue from schizophrenia, bipolar disorder, and psychiatric-free controls (n = 35 in each group) were subject to SELDI-TOF-MS protein profiling. There were 13 protein peaks distinguishing schizophrenia versus control and 15 in bipolar versus control. Using a predictor set of 10 peaks for each comparison, 73% prediction accuracy (p = 2.3×10−4) was achieved. Three peaks were in common between schizophrenia and bipolar disorder.
This pilot study found protein profiles that distinguished schizophrenia and bipolar patients from controls and notably from each other. Identifying and characterizing the proteins in this study may elucidate neuropsychiatric phenotypes and uncover therapeutic targets. Further, applying class prediction bioinformatics may allow the clinician to differentiate the two phenotypes by profiling CSF or even serum.
Chronic traumatic encephalopathy (CTE) is a form of neurodegeneration that results from repetitive brain trauma. Not surprisingly, CTE has been linked to participation in contact sports such as boxing, hockey and American football. In American football getting "dinged" equates to moments of dizziness, confusion, or grogginess that can follow a blow to the head. There are approximately 100,000 to 300,000 concussive episodes occurring in the game of American football alone each year. It is believed that repetitive brain trauma, with or possibly without symptomatic concussion, sets off a cascade of events that result in neurodegenerative changes highlighted by accumulations of hyperphosphorylated tau and neuronal TAR DNA-binding protein-43 (TDP-43). Symptoms of CTE may begin years or decades later and include a progressive decline of memory, as well as depression, poor impulse control, suicidal behavior, and, eventually, dementia similar to Alzheimer's disease. In some individuals, CTE is also associated with motor neuron disease similar to amyotrophic lateral sclerosis. Given the millions of athletes participating in contact sports that involve repetitive brain trauma, CTE represents an important public health issue.
In this review, we discuss recent advances in understanding the etiology of CTE. It is now known that those instances of mild concussion or "dings" that we may have previously not noticed could very well be causing progressive neurodegenerative damage to a player's brain. In the future, focused and intensive study of the risk factors could potentially uncover methods to prevent and treat this disease.
Traumatic brain injury; TDP-43; Taupathy; Dementia; Contact sports; Neurodegeneration; Concussion
Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered.
Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.
α7-nicotinic acetylcholine receptor; ulcerative colitis; enteric nervous system; pro-inflammatory cytokines
Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder's pathogenesis.
Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut.
If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients.
Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal.
An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events.
A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate.
Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.
Statin therapy is considered an effective measure for the prevention of ischemic stroke. Several recent studies have indicated that treatment with statins, prior to the onset of acute ischemic stroke, may also substantially reduce the severity of stroke and the degree of patient disability. The purpose of the present review is to systematically evaluate the effectiveness of statin pretreatment on functional outcome of acute ischemic stroke and to assess potential adverse events associated with statin use.
Relevant articles on the role of statins in acute ischemic stroke were identified via MEDLINE/PubMed, EMBASE, CENTRAL, and by manual searches of the references of identified papers. Clinical studies (most were prospective cohort studies) assessing statin therapy for acute ischemic stroke were selected for the review. Only two randomized controlled clinical trials met the criteria to be included in the analysis. Clinical outcome was assessed based on the degree of disability determined with the modified Rankin Scale (mRS) and Barthel index (BI). The National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity. Recurrence of stroke in patients who had suffered from a previous stroke was analyzed with and without statin therapy. Incidence and severity of adverse reactions was reviewed. Because there were too many differences in study outcome measures, a quantitative analysis of data was deemed inappropriate. A qualitative summary of the data was consequently completed.
Thirteen reports were systematically reviewed to evaluate the efficacy and safety of statins in the pretreatment of acute ischemic stroke. Pretreatment with statins was found to reduce the recurrence of stroke and to result in more favorable outcomes for patients. The beneficial effects of prior statin therapy in acute ischemic stroke were shown to be especially profound in whites, diabetics, elderly patients with hypertension and other vascular diseases, and in patients with ideal low density lipoprotein (LDL) levels. There were few incidences of adverse reactions with statin pretreatment, most of which were not statistically significant.
Pretreatment with statins was associated with a favorable outcome in acute ischemic stroke, with few incidences of adverse reactions.
Inflammatory bowel disease is a chronic intestinal inflammatory condition, the pathology of which is incompletely understood. Gut inflammation causes significant changes in neurally controlled gut functions including cramping, abdominal pain, fecal urgency, and explosive diarrhea. These symptoms are caused, at least in part, by prolonged hyperexcitability of enteric neurons that can occur following the resolution of colitis. Mast, enterochromaffin and other immune cells are increased in the colonic mucosa in inflammatory bowel disease and signal the presence of inflammation to the enteric nervous system. Inflammatory mediators include 5-hydroxytryptamine and cytokines, as well as reactive oxygen species and the production of oxidative stress. This review will discuss the effects of inflammation on enteric neural activity and potential therapeutic strategies that target neuroinflammation in the enteric nervous system.
In spite of advances in psychotherapy and pharmacotherapy, there are still a significant number of patients with depression and obsessive-compulsive disorder that are not aided by either intervention. Although still in the experimental stage, deep brain stimulation (DBS) offers many advantages over other physically-invasive procedures as a treatment for these psychiatric disorders. The purpose of this study is to systematically review reports on clinical trials of DBS for obsessive-compulsive disorder (OCD) and treatment-resistant depression (TRD). Locations for stimulation, success rates and effects of the stimulation on brain metabolism are noted when available. The first observation of the effects of DBS on OCD and TRD came in the course of using DBS to treat movement disorders. Reports of changes in OCD and depression during such studies are reviewed with particular attention to electrode locations and associated adverse events; although these reports were adventitious observations rather than planned. Subsequent studies have been guided by more precise theories of structures involved in DBS and OICD. This study suggests stimulation sites and prognostic indicators for DBS. We also briefly review tractography, a relatively new procedure that holds great promise for the further development of DBS.
Articles were retrieved from MEDLINE via PubMed. Relevant references in retrieved articles were followed up. We included all articles reporting on studies of patients selected for having OCD or TRD. Adequacy of the selected studies was evaluated by the Jadad scale. Evaluation criteria included: number of patients, use of recognized psychiatric rating scales, and use of brain blood flow measurements. Success rates classified as "improved" or "recovered" were recorded. Studies of DBS for movement disorders were included if they reported coincidental relief of depression or reduction in OCD. Most of the studies involved small numbers of subjects so individual studies were reviewed.
While the number of cases was small, these were extremely treatment-resistant patients. While not everyone responded, about half the patients did show dramatic improvement. Associated adverse events were generally trivial in younger psychiatric patients but often severe in older movement disorder patients. The procedures differed from study to study, and the numbers of patients was usually too small to do meaningful statistics or make valid inferences as to who will respond to treatment.
DBS is considered a promising technique for OCD and TRD. Outstanding questions about patient selection and electrode placement can probably be resolved by (a) larger studies, (b) genetic studies and (c) imaging studies (MRI, fMRI, PET, and tractography).
For more than 20 years, researchers have attempted to identify diagnostic and prognostic biomarkers for psychiatric disorders including schizophrenia, major (unipolar) depression, and bipolar disorder. Advocates of this research contend that identifying such biomarkers will aid in the diagnosis of these disorders, as well as the possible development of effective psychiatric medications to treat them. Currently, there are no diagnostic tests available. This is largely due to the multi-factorial nature of psychiatric disorders. Biomarker testing of individuals is also prohibitively expensive because significant expertise is required to conduct tests and follow-up counseling for the patient is often necessary. It is cautioned that widespread biomarker testing could lead to negative consequences such as discrimination in health insurance and employment, as well as selective abortion.
Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.
We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.
Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.
We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.
Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies.
Brainstem gliomas are rare in adults. They most commonly occur in the pons and are most likely to be high-grade lesions. The diagnosis of a high-grade brainstem glioma is usually reached due to the presentation of rapidly progressing brainstem, cranial nerve and cerebellar symptoms. These symptoms do, however, overlap with a variety of other central nervous system disorders. Magnetic resonance imaging is the radiographic modality of choice, but can still be misleading.
A 48-year-old Caucasian woman presented with headache and vomiting followed by cerebellar signs and confusion. Magnetic resonance imaging findings were suggestive of a demyelinating process, but the patient failed to respond to therapy. Her condition rapidly progressed and she died. At autopsy, a high-grade invasive pontine tumor was identified. Histological evaluation revealed glioblastoma multiforme.
While pontine gliomas are rare in adults, those that do occur tend to be high-grade and rapidly progressive. Progression of symptoms from non-specific findings of headache and vomiting to rapid neurological deterioration, as occurred in our patient, is common in glioblastoma multiforme. While radiographic findings are often suggestive of the underlying pathology, this case represents the possibility of glioblastoma multiforme presenting as a deceptively benign appearing lesion.
While hypertension is a leading risk factor for an initial stroke, the role of blood pressure lowering to prevent subsequent stroke is less clear. The results of recent large clinical trials investigating effects of antihypertensive agents in patients with a history of stroke have not shown a significant benefit; findings that are at odds with previous data. Our meta-analysis systematically evaluates the available, relevant trials to examine the role of antihypertensive drugs in preventing recurrent stroke.
MEDLINE, CENTRAL, and ClinicalTrials.gov were systematically searched and bibliographies from key reports were examined. All randomized, placebo-controlled trials that tested blood pressure lowering agents in patients with stroke or transient ischemic attack were identified. The results from these trials were combined and meta-analyses were performed.
Ten studies were found to contain relevant endpoints and presented data allowing meta-analysis. Agents that lowered blood pressure reduced recurrent stroke (OR 0.71, 95% CI 0.59-0.86, P = 0.0004) and cardiovascular events (OR 0.69, 95% CI 0.57-0.85, P = 0.0004) in patients with a previous stroke or TIA. These agents did not affect the rate of myocardial infarction (OR 0.86, 95% CI 0.73-1.01, P = 0.07) or all-cause mortality (OR 0.95, 95% CI 0.83-1.07, P = 0.39) in this patient population.
Despite recent large trials showing no significant effect, in patients that have experienced a TIA or stroke, blood pressure lowering agents reduced the occurrence of subsequent stroke and cardiovascular events. The rate of myocardial infarction and all-cause mortality was unchanged.