Long-lasting Symptoms Research Articles

A 20-year prospective longitudinal MRI study on cervical spine after whiplash injury: Follow-up of a cross-sectional study

BackgroundSome patients suffer from long-lasting symptoms after whiplash injury. However, there are few reports on the long-term changes in the cervical spine after whiplash injury using imaging tests. The purpose of this longitudinal study was to determine the changes on MRI of the cervical spine 20 years after whiplash injury, and to examine the relationships between changes in the cervical spine on MRI and changes in related clinical symptoms. MethodsEighty-one subjects finally participated in this study (follow-up rate 16%). The mean follow-up duration was 21.7 years. All subjects filled out a questionnaire about their clinical symptoms. The MRI findings were assessed using numerical grading system applied in the original study. Statistic analyses were used to investigate whether the progression of each MRI finding was associated with the severity of neck pain, stiff shoulders, dizziness and tinnitus. ResultsAll subjects had complained of some clinical symptoms in the original study: 71 had neck pain, 53 stiff shoulders, and others. In the present study, 66 subjects (81.5%) complained of some clinical symptoms: 57 had stiff shoulders, 20 neck pain, and others. The progression of degeneration on MRI was observed in 95% of the subjects, with C4/5 and 5/6 being the most frequently involved levels. Changes in the severity of neck pain, stiff shoulders, dizziness and tinnitus over 20 years were not significantly associated with the progression of degenerative changes in the cervical spine on MRI. ConclusionsTwenty years after whiplash injury, 95% of the subjects showed a progression of degeneration in the cervical spine. The progression of the intervertebral disc degeneration in the cervical spine on MRI after whiplash injury was not significantly associated with changes in the severity of related clinical symptoms, indicating that the degenerative changes on MRI may reflect the physiological aging process rather than post-traumatic sequelae.

Oxaliplatin induces pH acidification in dorsal root ganglia neurons

Oxaliplatin induced peripheral neurotoxicity is characterized by an acute cold-induced syndrome characterized by cramps, paresthesias/dysesthesias in the distal limbs and perioral region, that develops rapidly and lasts up to one week affecting nearly all the patients as well as by long-lasting symptoms. It has been previously shown that pharmacological or genetic ablation of TRPA1 responses reduces oxaliplatin-induced peripheral neurotoxicity in mouse models. In the present report, we show that treatment with concentrations of oxaliplatin similar to those found in plasma of treated patients leads to an acidification of the cytosol of mouse dorsal root ganglia neurons in culture and this in turn is responsible for sensitization of TRPA1 channels, thereby providing a mechanistic explanation to toxicity of oxaliplatin. Reversal of the acidification indeed leads to a significantly reduced activity of TRPA1 channels. Last, acidification occurs also in vivo after a single injection of therapeutically-relevant doses of oxaliplatin.

Biographical suspension and liminality of Self in accounts of severe sciatica

Sciatica is a common form of low back pain (LBP) that has been identified as distinct both in terms of the persistence and severity of symptoms. Little research has explored individual experiences of sciatica, and none focuses on individuals with the most severe, long-lasting symptoms who may experience the most profound impact. This paper addresses this gap through proposing a theoretical framework for understanding such experiences, that of biographical suspension as a form of liminality of Self. Twenty semi-structured interviews were conducted with individuals with severe sciatic symptoms between January 2016‒March 2017, as part of the UK-based SCOPiC (SCiatica Outcomes in Primary Care) randomised controlled trial. Data were analysed thematically using the constant comparison method. The concept of ‘biographical suspension’, originally developed in LBP, emerged as one whereby individuals put life on-hold in the expectation of an eventual return to their former, pain-free selves. Deeper analysis extended this concept to a form of liminality, whereby individuals are caught between pre- and post-sickness selves, unable to fully identify with either. This liminality is underpinned by ongoing beliefs about sciatica as a temporary and fixable ‘injury’ rather than long-term ‘illness’, even among those with long-lasting symptoms. This led to a disjuncture between individuals' ongoing pain beliefs and experiences, resulting in longer-term psychological impacts. Biographical suspension is further conceptualised as an experiential stage giving rise to four distinct short-term trajectories: i) symptom resolution leading individuals to occupy a clearly post-liminal state; ii) remaining in suspended liminality; iii) ongoing symptoms leading to a post-liminal state of resignation; ix) a state of being both between sickness and wellness, and straddling hope and fear; thus exemplifying differing states of liminality experienced over time. Findings have implications for the support provided in clinical settings to individuals who may struggle to self-manage due to sustained liminality of Self.

Paths of causal influence from prenatal inflammation and preterm gestation to childhood asthma symptoms

Introduction: Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. The aim was to investigate paths of assumed causality leading from foetal inflammatory response syndrome (FIRS) to asthma symptoms in preterms. Methods: Demographic, antenatal, delivery and outcome data were collected from 262 infants with less than 32 completed weeks of gestational age over a 10-year period in a prospective cohort study. The presence of symptoms of asthma beyond the age of 5 years was the primary outcome measure. The causal effect of FIRS on childhood asthma was tested with three different logistic regression models and two structural equation models (SEM). Results: FIRS (OR = 4.7) and subsequent chronic lung disease of prematurity (OR = 7.7) and early childhood wheezing (OR = 9.5) are the most important risk factors for development of asthma symptoms in children born with less than 32 weeks of gestational age. The path analysis showed that FIRS has a large direct (0.59), medium indirect (0.11) and large overall (0.70) effect on CLD; large negative direct effect on ECW (−0.34) and a large positive indirect effect (0.74), mediated by CLD. On the occurrence of asthma symptoms, FIRS has a medium negative direct effect (−0.18) and a medium positive indirect effect (0.26), mediated by CLD and ECW. Conclusion: Prenatal inflammation plays an important role in the development of chronic respiratory disturbances in preterm infants. This influence is mainly related to structural and developmental lung abnormalities initiated in utero as consequences of FIRS, resulting in CLD of prematurity, and overcoming the protective mechanisms of chorioamnionitis.

Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach

Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). Moreover, we examined whether there were sex-specific attributes of these functional brain abnormalities and whether functional brain abnormalities in patients is related to pain intensity characteristics on different time scales. We acquired resting-state functional MRI and quantified frequency-specific regional LFOs in chronic pain patients with ankylosing spondylitis. We found that patients exhibit frequency-specific aberrations in LFOs. Specifically, lower-frequency (slow-5) abnormalities were restricted to the ascending pain pathway (thalamus and S1), whereas higher-frequency abnormalities also included the default mode (i.e., posterior cingulate cortex; slow-3, slow-4) and salience (i.e., mid-cingulate cortex) networks (slow-4). Using a machine learning approach, we found that these abnormalities, in particular within higher frequencies (slow-3), can be used to make generalizable inferences about patients' average pain ratings (trait-like pain) but not current (i.e., state-like) pain levels. Furthermore, we identified sex differences in LFOs in patients that were not present in healthy controls. These novel findings reveal mechanistic brain abnormalities underlying the longer-lasting symptoms (trait pain intensity) in chronic pain.SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.

Emergency room intervention to prevent post concussion-like symptoms and post-traumatic stress disorder. A pilot randomized controlled study of a brief eye movement desensitization and reprocessing intervention versus reassurance or usual care

Up to 20% of patients presenting at an emergency room (ER) after a stressful event will for several months suffer from very diverse long-lasting symptoms and a potentially significant decline in quality of life, often described as post concussion-like symptoms (PCLS). The objectives of our randomized open-label single-center study were to assess the feasibility of psychologist-led interventions in the context of the ER and to compare the effect of eye movement desensitization and reprocessing (EMDR) with reassurance and usual care. Conducted in the ER of Bordeaux University Hospital, the study included patients with a high risk of PCLS randomized in three groups: a 15-min reassurance session, a 60-min session of EMDR, and usual care. Main outcomes were the proportion of interventions that could be carried out and the prevalence of PCSL and post-traumatic stress disorder (PTSD) three months after the ER visit.One hundred and thirty patients with a high risk of PCLS were randomized. No logistic problem or patient refusal was observed. In the EMDR, reassurance and control groups, proportions of patients with PCLS at three months were 18%, 37% and 65% and those with PTSD were 3%, 16% and 19% respectively. The risk ratio for PCLS adjusted for the type of event (injury, non-injury) for the comparison between EMDR and control was 0.36 [95% CI 0.20–0.66].This is the first randomized controlled trial that shows that a short EMDR intervention is feasible and potentially effective in the context of the ER.The study was registered at ClinicalTrials.gov (NCT03194386).

The Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry: rationale and design

Uterine fibroids are common in premenopausal women, yet comparative effectiveness research on uterine fibroid treatments is rare. The purpose of this study was to design and establish a uterine fibroid registry based in the United States to provide comparative effectiveness data regarding uterine fibroid treatment. We report here the design and initial recruitment forthe Comparing Options for Management: Patient-centered REsults forUterine Fibroids (COMPARE-UF) registry (Clinicaltrials.gov, NCT02260752), funded by the Agency for Healthcare Research and Quality in collaboration with the Patient-Centered Outcomes Research Institute. COMPARE-UF was designed to help answer critical questions about treatment options for women with symptomatic uterine fibroids. Women who undergo a procedure for uterine fibroids (hysterectomy, myomectomy [abdominal, hysteroscopic, vaginal, and laparoscopic/robotic], endometrial ablation, radiofrequency fibroid ablation, uterine artery embolization, magnetic resonance-guided focused ultrasound, or progestin-releasing intrauterine device insertion) at 1 of the COMPARE-UF sites are invited to participate in a prospective registry with 3 years follow up for postprocedural outcomes. Enrolled participants provide annual follow-up evaluation through an online portal or through traditional phone contact. A central data abstraction center provides information obtained from imaging, operative or procedural notes, and pathology reports. Women with uterine fibroids and other stakeholders are a key part of the COMPARE-UF registry and participate at all points from study design to dissemination of results. We built a network of 9 clinical sites across the United States with expertise in the care of women with uterine fibroids to capture geographic, racial, ethnic, and procedural diversity. Of the initial 2031 women who were enrolled in COMPARE-UF, 42% are self-identified as black or African American, and 40% are ≤40 years old, with 16% of participants <35 years old. Women who undergo myomectomy comprise the largest treatment group at 46% of all procedures, with laparoscopic or robotic myomectomy comprising the largest subset of myomectomies at 19% of all procedures. Hysterectomy is the second most common treatment within the registry at 38%. In response to priorities that were identified by our patient stakeholders, the initial aims within COMPARE-UF will address how different procedures that are used to treat uterine fibroids compare in terms of long-lasting symptom relief, potential for recurrence, medical complications, improvement in quality of life and sexual function, age at menopause, and fertility and pregnancy outcomes. COMPARE-UF will generate evidence on the comparative effectiveness of different procedural options for uterine fibroids and help patients and their caregivers make informed decisions that best meet an individual patient's short- and long-term preferences. Building on this infrastructure, the COMPARE-UF team of investigators and stakeholders, including patients, collaborate to identify future priorities for expanding the registry, such as assessing the efficacy of medical therapies for uterine fibroids. COMPARE-UF results will be disseminated directly to patients, providers, and other stakeholders by traditional academic pathways and by innovative methods that include a variety of social media platforms. Given demographic differences among women who undergo different uterine fibroid treatments, the assessment of comparative effectiveness for this disease through clinical trials will remain difficult. Therefore, this registry provides optimized evidence to help patients and their providers better understand the pros and cons of different treatment options so that they can make more informed decisions.

Sedentary Behavior Predicts Headache Pain Following Mild Traumatic Brain Injury

The acute management of mild traumatic brain injury (mTBI), particularly in athletes, typically includes a period of physical rest during symptom resolution. However, evidence for the use of rest versus physical activity to aid in mTBI recovery is mixed and may depend on symptom type and severity. Post-traumatic headaches (PTH) are one of the most common and long-lasting symptoms of mTBI. While physical activity is often used in the non-pharmacological management of primary headache disorders, the relationship between PTH’s and physical activity behavior in the first month post-injury remains poorly understood. PURPOSE: To determine if self-reported physical activity behavior predicts headache pain in mTBI patients within 1 month of head injury, and whether psychological factors mediate this relationship. METHODS: Twenty-seven mTBI patients recruited from Emergency Departments completed study sessions at 1-2 weeks and 1-month post head injury. The McGill Pain Questionnaire (MPQ) provided a quantitative evaluation of the patient’s headache pain experience. The International Physical Activity Questionnaire - short form assessed the amount of time in the past week participants spent on vigorous and moderate intensity activity, walking, and sitting. Participants also completed the Pain Catastrophizing Scale, which assesses negative mental responses to anticipated or actual pain. Simple and multiple linear regressions were used to test whether physical activity behavior and pain catastrophizing predicted headache pain at 1 month post injury, and whether pain catastrophizing mediated this relationship. RESULTS: Separate simple regression analyses indicated the following: 1) time sitting at 2 weeks post-injury predicted pain on the MPQ at 1 month (B=.41, p=.035), 2) time sitting at 2 weeks predicted pain catastrophizing at 1 month (B=.38, p=.049), 3) pain catastrophizing predicted pain on the MPQ at 1 month (B=.53, p=.003). When pain catastrophizing and time sitting were both entered as predictors into the same regression model, pain catastrophizing was the only significant predictor of pain on the MPQ. CONCLUSIONS: Results suggest that increased sitting in the acute stage of mTBI predicted greater headache pain in the subacute stage of injury, and this relationship was mediated by pain catastrophizing.

Long-term neurological and neuropsychological complications of sulfur mustard and Lewisite mixture poisoning in Chinese victims exposed to chemical warfare agents abandoned at the end of WWII

In August 2003, 44 victims were poisoned by chemical warfare agents (CWAs) leaked from five drums that were excavated at a construction site in Qiqihar, Northeast China. The drums were abandoned by the former Japanese imperial army during World War II and contained a mixture of Sulfur mustard (SM) and Lewisite. We carried out a total of six regular check-ups between 2006 and 2014, and from 2008 we added neurological evaluations including neuropsychological test and autonomic nervous function test in parallel with medical follow-up as much as was possible. Severe autonomic failure, such as hyperhidrosis, pollakiuria, diarrhoea, diminished libido, and asthenia appeared in almost all victims. Polyneuropathy occurred in 35% of the victims and constricted vision occurred in 20% of them. The rates of abnormal response on cold pressor test (CPT), active standing test (AST), Heart rate variability (CVR-R), performed in 2014, were 63.1%, 31.6%, and 15.9%, respectively. On neuropsychological testing evaluated in 2010, a generalized cognitive decline was observed in 42% of the victims. Memories and visuospatial abilities were affected in the remaining victims. Finally, a 17-item PTSD questionnaire and the Beck Depression Inventory evaluated in 2014 revealed long-lasting severe PTSD symptoms and depression of the victims. Our findings suggest that an SM/Lewisite compound have significant adverse consequences directly in cognitive and emotional network and autonomic nervous systems in the brain.

Anderson-Fabry disease.

Anderson-Fabry disease.

Molecular role of dopamine in anhedonia linked to reward deficiency syndrome (RDS) and anti- reward systems.

Anhedonia is a condition that leads to the loss of feelings pleasure in response to natural reinforcers like food, sex, exercise, and social activities. This disorder occurs in addiction, and an array of related neuropsychiatric syndromes, including schizophrenia, depression, and Post Traumatic Stress Disorder (PTSD). Anhedonia may by due to derangements in mesolimbic dopaminergic pathways and their terminal fields (e.g., striatum, amygdala, and prefrontal cortex) that persist long after the traces of the causative drugs are eliminated (pharmacokinetically). Here we postulate that anhedonia is not a distinct entity but is rather an epiphenomenon of hypodopaminergic states and traits arising from the interaction of genetic traits and epigenetic neurobiological alterations in response to environmental influences. Moreover, dopaminergic activity is rather complex, and so it may give rise to differential pathophysiological processes such as incentive sensitization, aberrant learning and stress-like "anti-reward" phenomena. These processes may have additive, synergistic or antagonistic interactions with the concurrent reward deficiency states leading in some instances to more severe and long-lasting symptoms. Operant understanding of the neurogenetic antecedents to reward deficiency syndrome (RDS) and the elucidation of reward gene polymorphisms may provide a map for accessing an individual's genetic risk for developing Anhedonia. Prevention techniques that can restore homeostatic balance via physiological activation of dopaminergic receptors (D2/D3) may be instrumental for targeting not only anhedonia per se but also drug craving and relapse.

Success factors for adherence in hyposensitization.

For the success of an immunotherapy regimen, adherence is a major success factor. The goal of our study was to identify the factors that positively and negatively influence patient compliance, and to create strategies to improve it. Four questionnaires were designed for different patient groups: A – after immunotherapy; B – during immunotherapy; C – before immunotherapy; D – no experience with immunotherapy. From March to October 2008, 790 questionnaires were collected. For the first group, questionnaire A was answered by 272 patients. Of these, 15.8% had dropped out of immunotherapy. Women had higher dropout rates than men (16.8% vs. 12.3%). The following aspects of immunotherapy were viewed by the patients as negative: time consuming (69.5%), adverse reactions (62.5%), insufficient patient information (53.7%), no change in use of symptomatic medication (33.8%) and no change in symptoms (60.7%). Despite the mentioned drawbacks, 74% of all patients would still recommend allergen immunotherapy. Questionnaire B was completed by 281 patients. In this group, 8.7% had already considered dropping out. The following unfavourable aspects were identified: time consuming (66.2%), adverse reactions (61.9%), insufficient patient information (54.8%), no change in symptoms (51.2%) and use of symptomatic medication (47.0%). Despite this, up to 95.4% of all patients would recommend immunotherapy. Questionnaire C was filled-out by 55 patients. The following reasons were rated by the patients as “important” or “very important” for the decision to start hyposensitization: long-lasting symptom alleviation (100%), few adverse reactions (98.2%), comprehensive patient information (96.3%), easy integration into daily routine (89.1%), re-assessment of therapy by doctor (83.3%) and reduced need for symptomatic medication (81.8%). Questionnaire D was filled in by 182 participants. 89% had already heard the term hyposensitization before. Their general knowledge regarding this therapy was average (3.23 on a scale of 1 – 6; where 1 = optimum). Long-lasting symptom alleviation (99.5%), comprehensive patient information (97.8%), easy integration into daily routine (96.1%), reduced symptomatic medication use (92.6%) and re-assessment by doctor (88.8%) were considered “very important” or “important” characters in the desired immunotherapy regime. Adherence to the hyposensitization schedule is essential for its success. The treating doctor should aim at choosing the right therapy and working out an individualized patient treatment plan. Equally important is providing information to the patient throughout the duration of the treatment. The doctor should assist the patient to create an optimized time schedule to help make the therapy less time-consuming.

Long-Lasting Voice-Related Symptoms in Patients Without Vocal Cord Palsy After Thyroidectomy.

Some patients complain of long-lasting voice symptoms after thyroid surgery without objective vocal fold pathology. We assessed the factors that may influence voice symptoms more than 12months after thyroidectomy. We performed a retrospective analysis of 68 patients from July 2010 to May 2012. The voices of all patients were analyzed before and after thyroid surgery (2weeks and 2, 4, 6, 8, 10, and 12months after surgery). According to the recovery of postoperative voice symptoms, patients were divided into two groups: the non-recovery group and the recovery group. Voice symptoms were measured using a thyroidectomy-related voice questionnaire (TVQ). We compared voice analysis data for each group and investigated the factors related to long-lasting postoperative voice symptoms. Forty-nine patients were included in the recovery group, and 19 patients were included in the non-recovery group. No differences in sex ratio, tumor size, and surgical extent were found between the groups. However, the proportion of professional voice users (odds ratio 4.121; 95% confidence interval 0.983-17.267; p<0.043) was significantly higher in the non-recovery group. The cutoff score of the TVQ, at 2months after thyroid surgery, for the differentiation of the recovery and non-recovery groups was 25, and the sensitivity and specificity values were 84.2 and 87.8%, respectively. Professional voice users may be presented long-lasting voice symptoms after thyroid surgery. The cutoff TVQ score of 25, at 2months after thyroid surgery, may be a guideline for counseling patients who have voice symptoms.

Psychiatric symptoms after acute respiratory distress syndrome: a 5-year longitudinal study.

We aimed to characterize anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms over 5-year follow-up after acute respiratory distress syndrome (ARDS) and determine risk factors for prolonged psychiatric morbidity. This prospective cohort study enrolled patients from 13 medical and surgical intensive care units in four hospitals, with follow-up at 3, 6, 12, 24, 36, 48, and 60months post-ARDS. Trained research staff administered the Hospital Anxiety and Depression Scale (HADS) (scores≥8 on anxiety and depression subscales indicating substantial symptoms) and the Impact of Event Scale-Revised (IES-R, scores≥1.6 indicating substantial PTSD symptoms) at each follow-up visit. Of 196 consenting survivors, 186 (95%) completed HADS and IES-R assessments; 96 (52%) had any continuous or recurring (prolonged) symptoms, and 71 (38%), 59 (32%), and 43 (23%) had prolonged anxiety, depression, and PTSD symptoms, respectively (median total durations 33-39months, 71-100% of observed follow-up time). Prolonged psychiatric symptoms tended to co-occur across domains; the most common morbidity pattern involved substantial symptoms in all three domains. Worse pre-ARDS mental health, including prior depression and psychological distress in the period immediately preceding ARDS, was strongly associated with prolonged post-ARDS psychiatric morbidity across symptom domains. Clinically significant and long-lasting symptoms of anxiety, depression, and PTSD are common in the first 5years after ARDS. In-hospital screening of psychiatric history, including recent anxiety and depression symptoms, may be useful for long-term mental health treatment planning after ARDS.

Potential of microRNAs as novel targets in the alleviation of pathological fear.

The current treatment of post-traumatic stress disorder (PTSD), phobias and other anxiety disorders, remains insufficient particularly in producing long-lasting full symptom control. Dysfunctional fear processing is common in these disorders, including a deficiency in fear-inhibitory mechanisms and impairment in the ability to discriminate between safety and danger cues. Research has aimed to elucidate brain circuitries, neurotransmitters and downstream signaling pathways important in the alleviation of aberrant fear, with a specific focus on mechanisms modulating fear memory and its behavioral expression. MicroRNAs (miRNA) as "fine tuners" of gene expression at the post-transcriptional level have emerged as critical regulators of such mechanisms important in both, the generation and the inhibition of fear memories. Along these lines, abnormal expression of miRNAs has been associated with different fear-related disorders. After providing an updated overview on the involvement of miRNAs in fear learning mechanisms, we summarize and discuss in particular those studies in which the implication of miRNAs in successful inhibition of fear has been explored. For a better overview, we dissociate the different modes of fear alleviation investigated in this regard and present studies in rodents demonstrating that specific miRNAs are involved in the destabilization of fear by interfering with consolidation/reconsolidation mechanisms or that they are associated with the generation of fear extinction or safety learning. Finally, we discuss the potential of miRNAs as biomarkers and novel therapeutic targets, as well as the challenges involved in applying the discovered mechanisms in the development of improved treatments of fear- and trauma-related disorders.

Combined cognitive and vocational interventions after mild to moderate traumatic brain injury: study protocol for a randomized controlled trial

BackgroundA considerable proportion of patients with mild to moderate traumatic brain injury (TBI) experience long-lasting somatic, cognitive, and emotional symptoms that may hamper their capacity to return to work (RTW). Although several studies have described medical, psychological, and work-related factors that predict RTW after TBI, well-controlled intervention studies regarding RTW are scarce. Furthermore, there has traditionally been weak collaboration among health-related rehabilitation services, the labor and welfare sector, and workplaces.Methods/designThis study protocol describes an innovative randomized controlled trial in which we will explore the effect of combining manualized cognitive rehabilitation (Compensatory Cognitive Training [CCT]) and supported employment (SE) on RTW and related outcomes for patients with mild to moderate TBI in real-life competitive work settings. The study will be carried out in the southeastern region of Norway and thereby be performed within the Norwegian welfare system. Patients aged 18–60 years with mild to moderate TBI who are employed in a minimum 50% position at the time of injury and sick-listed 50% or more for postconcussive symptoms 2 months postinjury will be included in the study. A comprehensive assessment of neurocognitive function, self-reported symptoms, emotional distress, coping style, and quality of life will be performed at baseline, immediately after CCT (3 months after inclusion), following the end of SE (6 months after inclusion), and 12 months following study inclusion. The primary outcome measures are the proportion of participants who have returned to work at 12-month follow-up and length of time until RTW, in addition to work stability as well as work productivity over the first year following the intervention. Secondary outcomes include changes in self-reported symptoms, emotional and cognitive function, and quality of life. Additionally, a qualitative RTW process evaluation focused on organizational challenges at the workplace will be performed.DiscussionThe proposed study will combine cognitive and vocational rehabilitation and explore the efficacy of increased cross-sectoral collaboration between specialized health care services and the labor and welfare system. If the intervention proves effective, the project will describe the cost-effectiveness and utility of the program and thereby provide important information for policy makers. In addition, knowledge about the RTW process for persons with TBI and their workplaces will be provided.Trial registrationClinicalTrials.gov, NCT03092713. Registered on 10 March 2017.

The many faces of primary cauda equina myxopapillary ependymoma: clinicoradiological manifestations of two cases and review of the literature

Abstract Introduction: Myxopapillary ependymoma (MPE) is a benign and slow growing tumor that originates exclusively from the conus medullaris and cauda equina nervous tissue. It occurs more commonly in young patients. In addition, clinical presentations are non-specific and may mimic benign conditions. Magnetic resonance imaging (MRI) is the imaging modality of choice for evaluating this tumor. We hereby report on two young patients with long-lasting non-specific symptoms, which were clinically attributed to benign conditions. However, cauda equina tumor was revealed on MRI in both patients. Case report: Two cases of cauda equina MPE, a 19-year-old female and a 38-year-old male, with different clinical manifestations are reported. The first patient presented with paresis and paresthesia of the lower limbs, and the second patient’s complaint was chronic low-back pain and urinary incontinence. In both cases, MRI detected a tumor originated from the cauda equina, and histopathologic examination was compatible with MPE. Conclusion: Cauda equina tumors should be considered as a differential diagnosis in the young patients presented with neurologic deficits in the lower limbs, sphincter or erectile dysfunction, and even a simple low-back pain (particularly when symptoms are long-lasting and/or progressive).

Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability, yet the mechanisms underlying the chronic cognitive deficits associated with TBI remain unknown. Consequently, there are no effective treatments for patients suffering from the long-lasting symptoms of TBI. Here, we show that TBI persistently activates the integrated stress response (ISR), a universal intracellular signaling pathway that responds to a variety of cellular conditions and regulates protein translation via phosphorylation of the translation initiation factor eIF2α. Treatment with ISRIB, a potent drug-like small-molecule inhibitor of the ISR, reversed the hippocampal-dependent cognitive deficits induced by TBI in two different injury mouse models-focal contusion and diffuse concussive injury. Surprisingly, ISRIB corrected TBI-induced memory deficits when administered weeks after the initial injury and maintained cognitive improvement after treatment was terminated. At the physiological level, TBI suppressed long-term potentiation in the hippocampus, which was fully restored with ISRIB treatment. Our results indicate that ISR inhibition at time points late after injury can reverse memory deficits associated with TBI. As such, pharmacological inhibition of the ISR emerges as a promising avenue to combat head trauma-induced chronic cognitive deficits.

LASH: A Review of the Current Literature

The purpose of this review is to evaluate and explain our current understanding of a very rare disorder, long-lasting autonomic symptoms with associated hemicranias (LASH). At present, there are four known cases in the literature of LASH. Its characteristics and reported response to indomethacin link it most closely to the trigeminal autonomic cephalalgias (TACs). Its pathophysiology and epidemiology remain unclear. Variance in the pain and autonomic symptom relationship in the existing TAC literature along with the reports of TAC sine headache suggests that LASH may represent a far end of the spectrum of TACs, with most similarities to paroxysmal hemicrania (PH) and hemicrania continua (HC).

ALCOHOL ABUSE AND NEUROPSYCHIATRIC INVENTORY BEHAVIORAL SYMPTOMS IN THE NACC DATABASE

Alcohol abuse affects brain health throughout life. Alcoholic dementia is a controversial subject, but alcohol abuse may impact individuals across the cognitive spectrum over long periods of time. The National Alzheimer Coordinating Center (NACC) UDS includes questions about alcohol and other substance abuse, both recent and remote. We examined the behavioral and cognitive impact of recent and remote alcohol abuse. Subjects were 33208 NACC cases at initial evaluation with known alcohol abuse history without illicit substance abuse history. Alcohol/Substance abuse was defined as work, driving, legal, or social impairment over 1 year. Subjects were never-abusers (N=31558), remote abusers (abuse > 1 year ago) (N=1337), or recent abusers (N=313) (abuse ≤ 1 year ago) and “ever”. Subjects were stratified by Clinical dementia rating and compared items using two-sample t-tests. Ever-abusers reported more NPI-Q items than never-abusers in all CDR groups, and all racial/ethnic groups. NPI-Q item analysis showed significantly more Anxiety and Appetite changes in CDR0, all items except Delusions and Elation in CDR0.5 and all items except Delusions, Anxiety and Apathy in CDR1–3. Never abusers had significantly higher NPI-Q scores and more items endorsed than remote abusers for each CDR stage, except CDR=3 which had a small N(Never Abusers N=1040 vs. Any Abuse N=74). CDR-SB did not differ significantly between Never Abusers and those with history of abuse. Our results associate alcohol abuse with increased and more severe NPI-Q behavioral symptoms. Remote abusers exhibit more symptoms than never-abusers, supporting the hypothesis that alcohol abuse is associated with long-lasting behavioral symptoms. However, Alcohol abuse history does not appear to change functional socres based on CDR-SB. The NACC database is funded by NIA/NIH Grant U01 AG016976.