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ObjectiveEffective medical therapy and validated trial outcomes are lacking for small bowel Crohn’s disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion.DesignModified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures.ResultsIn this exercise, diagnosis of naïve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials.ConclusionStandardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.

Background and Aims Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn’s disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. Methods MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. Results In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate–severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. Conclusions MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.

Background. In monkey, reticulospinal connections to hand and forearm muscles are spontaneously strengthened following corticospinal lesions, likely contributing to recovery of function. In healthy humans, pairing auditory clicks with electrical stimulation of a muscle induces plastic changes in motor pathways (probably including the reticulospinal tract), with features reminiscent of spike-timing dependent plasticity. In this study, we tested whether pairing clicks with muscle stimulation could improve hand function in chronic stroke survivors. Methods. Clicks were delivered via a miniature earpiece; transcutaneous electrical stimuli at motor threshold targeted forearm extensor muscles. A wearable electronic device (WD) allowed patients to receive stimulation at home while performing normal daily activities. A total of 95 patients >6 months poststroke were randomized to 3 groups: WD with shock paired 12 ms before click; WD with clicks and shocks delivered independently; standard care. Those allocated to the device used it for at least 4 h/d, every day for 4 weeks. Upper-limb function was assessed at baseline and weeks 2, 4, and 8 using the Action Research Arm Test (ARAT), which has 4 subdomains (Grasp, Grip, Pinch, and Gross). Results. Severity across the 3 groups was comparable at baseline. Only the paired stimulation group showed significant improvement in total ARAT (median baseline: 7.5; week 8: 11.5; P = .019) and the Grasp subscore (median baseline: 1; week 8: 4; P = .004). Conclusion. A wearable device delivering paired clicks and shocks over 4 weeks can produce a small but significant improvement in upper-limb function in stroke survivors.

Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society for Pediatric Radiology, the American Gastroenterological Association, and other international experts recently reported consensus recommendations for standardized nomenclature for the interpretation and reporting of CT enterography and MR enterography findings of small bowel Crohn disease. The consensus recommendations included CT enterography and MR enterography bowel wall findings that are associated with Crohn disease, findings that occur with penetrating Crohn disease, and changes that occur in the mesentery related to Crohn disease. Also included were recommended radiology report impression statements that summarize the findings of small bowel Crohn disease at CT enterography and MR enterography. This article, authored by the Society of Abdominal Radiology Crohn's Disease-Focused Panel, illustrates the imaging findings and recommended radiology report impression statements described in the consensus recommendations with examples of CT enterography and MR enterography images. Additional interpretation guidelines for reporting CT enterography and MR enterography examinations are also presented. The recommended standardized nomenclature can be used to generate radiology report dictations that will help guide medical and surgical management for patients with small bowel Crohn disease.

Background:The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents. Methods:We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age Findings:Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9–5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1–17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patientsvs1 [vssix [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patientsvs12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group). Interpretation:This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes.

Objectives Falls are the leading cause of pediatric injury and account for the majority of emergency department injury visits, costing US $5 billion in medical costs annually. Epidemiology of pediatric falls has primarily been studied at single hospital centers and has not been analyzed statewide. We assessed pediatric falls across Maryland and geographically mapped them by census tract and block group. Methods The study used Maryland Health Services Cost Review Commission discharge data to retrospectively analyze the demographics and cross-sectional incidence rates of fall injuries in Maryland from 2013 to 2015. Geographical clusters were calculated for pediatric falls in Maryland and Baltimore City. Results From 2013 to 2015, Maryland hospitals discharged 738,819 pediatric patients, of whom 77,113 had fall injuries. Falls were more prevalent among males (56%), white race (55%), and patients with public insurance (56%). Over this period, 2 children who presented with fall injuries died. The incidence of falls did not vary from 2013 (27,481 children) to 2014 (27,261) and 2015 (26,451). Mapping fall injuries across Maryland identified Baltimore City as the primary cluster and rural pockets as secondary clusters of high incidence rates. Baltimore City maps showed a stable high-incidence cluster in the southwest region across all 3 years. Conclusions Pediatric fall injuries comprise a large volume of emergency department visits yet have a low mortality. Geographic mapping shows that fall incidence varies across the state and persists over time. Statewide geographic information can be used to focus resource management and target prevention strategies.

Patients with Crohn’s disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.

Background. Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery. Methods. We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer. Results. StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores. Conclusion. We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.

Mills’ syndrome is an idiopathic, slowly progressive, spastic hemiparesis. We describe three cases that have been under review for a minimum of 11 years (range 11–19). In all patients, symptoms started in a leg, with a mean age of onset of 59 years (range 53–63). The only abnormality on laboratory investigations was a mildly elevated CSF protein in one case. MRI demonstrated focal T2 hyper-intensity located eccentrically in the cervical cord ipsilateral to the symptomatic side. No cerebral abnormality was demonstrated. Whilst visual and somatosensory evoked potentials were unremarkable, motor evoked potentials were abnormal in all patients: central motor conduction times were significantly prolonged unilaterally in two patients and bilaterally but asymmetrically in the third. Beta-band (15–30 Hz) intermuscular coherence, a potentially more sensitive method of assessing upper motor neuron integrity, was absent unilaterally in one patient and bilaterally in the other two. One patient developed amyotrophy and thus a picture of amyotrophic lateral sclerosis after 16 years, suggesting that Mills’ syndrome is part of the motor neuron disease spectrum. Both amyotrophy and subclinical contralateral upper motor neuron disease can therefore be features of Mills’ syndrome. However, even with the most sensitive electrodiagnostic techniques, unilateral upper motor neuron disease can remain the only abnormality for as long as 10 years. We conclude that whilst Mills’ syndrome should be classified as a motor neuron disorder, it is a distinct nosological entity which can be distinguished from amyotrophic lateral sclerosis, upper motor neuron-dominant amyotrophic lateral sclerosis and primary lateral sclerosis. We propose diagnostic criteria for Mills’ syndrome, and estimate a point prevalence of at least 1.2:1,000,000 based on our well-defined referral population in the North of England.

Background and Aims Intestinal strictures are a common complication of Crohn’s disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. Methods We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). Results Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. Conclusions There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.

BACKGROUND & AIMS: No reliable method for evaluating intestinal fibrosis in Crohn’s disease (CD) exists; therefore, we developed a computed-tomography enterography (CTE)–based radiomic model (RM) for characterizing intestinal fibrosis in CD. METHODS: This retrospective multicenter study included 167 CD patients with 212 bowel lesions (training, 98 lesions; test, 114 lesions) who underwent preoperative CTE and bowel resection at 1 of the 3 tertiary referral centers from January 2014 through June 2020. Bowel fibrosis was histologically classified as none–mild or moderate–severe. In the training cohort, 1454 radiomic features were extracted from venous-phase CTE and a machine learning–based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers. The diagnostic performance of RM was compared with 2 radiologists’ visual interpretation of CTE using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate–severe from none–intestinal fibrosis was 0.888 (95% confidence interval [CI], 0.818–0.957). In the test cohort, the RM showed robust performance across 3 centers with an AUC of 0.816 (95% CI, 0.706–0.926), 0.724 (95% CI, 0.526–0.923), and 0.750 (95% CI, 0.560–0.940), respectively. Moreover, the RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort. Decision curve analysis showed that the RM provided a better net benefit to predicting intestinal fibrosis than the radiologists. CONCLUSIONS: A CTE-based RM allows for accurate characterization of intestinal fibrosis in CD.

Stricturing and penetrating disease are complications of Crohn disease (CD) that significantly affect patient outcomes. Careful evaluation for such complications is critical to the interpretation of magnetic resonance enterography. This manuscript outlines the key findings related to stricturing and penetrating CD and discusses current understanding of the pathophysiology and prognosis of complicated CD based on the literature.

Visual hallucinations (VH) are a common symptom of Parkinson's disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear although visual evoked potential (VEP) differences have been associated with VH at an earlier stage of PD. Here we compared the amplitude and latency pattern reversal VEPs in healthy controls (n = 21) and PDD patients (n = 34) with a range of VH severities. PDD patients showed increased N2 latency relative to controls, but no significant differences in VEP measures were found for patients reporting complex VH (CVH) (n = 17) compared to those without VH. Our VEP findings support previous reports of declining visual system physiology in PDD and some evidence of visual system differences between patients with and without VH. However, we did not replicate previous findings of a major relationships between the integrity of the visual pathway and VH.

INTRODUCTION: Fibrostenosis is a hallmark of Crohn’s disease (CD), remains a challenge in today’s clinical management of inflammatory bowel disease patients and represents a key event in the disease course necessitating improved preventative strategies and a multidisciplinary approach to diagnosis and management. With the advent of anti-fibrotic therapies and well-defined clinical endpoints for stricturing CD, there is promise to impact the natural history of disease. AREAS COVERED: This review summarizes current evidence in the natural history of stricturing Crohn’s disease, discusses management approaches as well as future perspectives on intestinal fibrosis. EXPERT OPINION: Currently, there are no specific therapies to prevent progression to fibrosis or to treat it after it becomes clinically apparent. In addition to the international effort by the Stenosis Therapy and Anti-Fibrotic Research (STAR) consortium to standardize definitions and propose endpoints in the management of stricturing CD, further research to improve our understanding of mechanisms of intestinal fibrosis will help pave the way for the development of future anti-fibrotic therapies.

Background:Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.Methods:During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.Findings:The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. Interpretation:To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. Funding: None.

Despite improvements in diagnostic criteria for dementia with Lewy bodies (DLB), the ability to discriminate DLB from Alzheimer’s disease (AD) and other dementias remains suboptimal. Electroencephalography (EEG) is currently a supportive biomarker in the diagnosis of DLB. We performed a systematic review to better clarify the diagnostic and prognostic role of EEG in DLB and define the clinical correlates of various EEG features described in DLB. MEDLINE, EMBASE, and PsycINFO were searched using search strategies for relevant articles up to 6 August 2020. We included 43 studies comparing EEG in DLB with other diagnoses, 42 of them included a comparison of DLB with AD, 10 studies compared DLB with Parkinson’s disease dementia, and 6 studies compared DLB with other dementias. The studies were visual EEG assessment (6), quantitative EEG (35) and event-related potential studies (2). The most consistent observation was the slowing of the dominant EEG rhythm (

Visual hallucinations (VH) are a common symptom of Parkinson’s disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear. Here we compared amplitude and latency patterns of reversal visual evoked potentials (VEPs) in healthy controls (n=21) and PDD patients (n = 34) with a range of VH severities. PDD patients showed increased N2 latency relative to controls, but patients reporting complex VH (n=17) did not demonstrate any relationship between VEP measurements and their hallucination severity as measured on the neuropsychiatric inventory hallucinations subscale (NPIHal) score. Our VEP findings support previous reports of declining visual system physiology in PDD. However, no notable major relationships between the integrity of the visual pathway and VH were found.

Fatigue is one of the most debilitating symptoms for people with multiple sclerosis (PwMS). By consolidating a diverse and conflicting evidence-base, this systematic review and meta-analysis aimed to gain new insights into the neurobiology of MS fatigue. MEDLINE, ProQuest, CINAHL, Web of Science databases and grey literature were searched using Medical Subject Headings. Eligible studies compared neuroimaging and neurophysiological data between people experiencing high (MS-HF) versus low (MS-LF) levels of perceived MS fatigue, as defined by validated fatigue questionnaire cut-points. Data were available from 66 studies, with 46 used for meta-analyses. Neuroimaging studies revealed lower volumetric measures in MS-HF versus MS-LF for whole brain (­22.74 ml; 95% CI: -37.72 to -7.76 ml; p = 0.003), grey matter (­18.81 ml; 95% CI: ­29.60 to ­8.03 ml; p p = 0.008) and acumbens (­0.09 ml; 95% CI: ­0.15 to ­0.03 ml; p = 0.003) and a higher volume of T1-weighted hypointense lesions (1.10 ml; 95% CI: 0.47 to 1.73 ml; p p = 0.02) and an attenuation of upper-limb (­5.77%; 95% CI:­8.61 to ­2.93%; p p = 0.04) skeletal muscle voluntary activation, accompanied by more pronounced upper-limb fatigability (­5.61%; 95% CI: -9.57 to -1.65%; p = 0.006) in MS-HF versus MS-LF. Results suggest that MS fatigue is characterised by greater cortico-subcortical grey matter atrophy and neural lesions, accompanied by neurophysiological decrements, which include reduced strength and voluntary activation. Prospero registration Prospero registration number: CRD42016017934

A 25-year-old woman presented to the neurology clinic describing 3 episodes of transient loss of consciousness over 9 months. The first 2 were unwitnessed, with no prodromal symptoms. The third event was a witnessed collapse while shopping. It was reported that both the patient's arms were stiff and by her sides with accompanied lateral tongue biting, a blue discoloration to her face, choking noises, and dilated pupils. The event lasted for less than 2 minutes, after which she was confused and drowsy. She remembered a premonitory feeling before the third collapse but found this difficult to describe.

Adipose tissue is present in close proximity to various organs in the human body. One prominent example is fat contained in the mesentery that is contiguous with all abdominal digestive organs including the intestine. Despite the fact that mesenteric fat-wrapping around the inflamed gut (so called "creeping fat") was described as a characteristic feature of Crohn's disease (CD) in the early 1930s, the functional implications of creeping fat have received only recent attention. As a potent producer of fatty acids, cytokines, growth factors, and adipokines, creeping fat plays an important role in regulation of immunity and inflammation. Increasing evidence points to a link between creeping fat and intestinal inflammation in CD, where histopathologic evaluation shows a significant association between creeping fat and connective tissue changes in the bowel wall, such as muscular hypertrophy, fibrosis, and stricture formation. In addition, emerging mechanistic data indicate a link between creeping fat, muscularis propria hyperplasia, and stricturing disease. Information on fat-mesenchymal interactions in other organs could provide clues to fill the fundamental knowledge gap on the role of distinct components of creeping fat in intestinal fibrosis and stricture formation. Future studies will provide important new information that in turn could lead to novel therapeutic agents aimed at prevention or treatment of CD-associated fibrosis and stricture formation.

Objectives Post marketing analysis of anti-epileptic drug (AED) efficacy and tolerability is of great value to the clinician since it is more representative of clinical practice than clinical trial data. We analyzed our experience with lacosamide (LCM) in patients treated after marketing. Patients and methods We identified all patients who were treated with LCM during the four year period after marketing, excluding patients who were in clinical trials. We recorded demographic data and analyzed efficacy and tolerability in patients who had at least one follow up visit or telephone call 3 months after the initiation of LCM. Results A total of 165 patients met our inclusion criteria. The mean age was 41 years. The majority of the cohort had focal epilepsy (146 patients) (88.4%). The mean duration of treatment was 31.2 months. Eighty one patients (49.1%) were continuing LCM at last follow up. Adverse effects (AEs) and discontinuation were significantly more common when LCM was added to one or more Na-channel blocking agents (NCB) (p = 0.0003 and 0.17). The 50% responder rate was 26% at 3 months and increased to 49% at 36 months. Patients were more likely to continue the drug and less likely to have AEs with slower titration over > 4 weeks (p = 0.02 for each). Four or more previously failed AEDs predicted poorer response rate compared to three or less AEDs (p = 0.001). Conclusion LCM use in clinical practice was associated with greater rate of seizure freedom than in clinical trials. Discontinuation and occurrence of AEs were significantly more likely with faster titration and adding LCM to NCB agents.

Computed tomography and magnetic resonance enterography have become routine small bowel imaging tests to evaluate patients with established or suspected Crohn's disease, but the interpretation and use of these imaging modalities can vary widely. A shared understanding of imaging findings, nomenclature, and utilization will improve the utility of these imaging techniques to guide treatment options, as well as assess for treatment response and complications. Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of Pediatric Radiology, the American Gastroenterological Association, and other experts, systematically evaluated evidence for imaging findings associated with small bowel Crohn's disease enteric inflammation and established recommendations for the evaluation, interpretation, and use of computed tomography and magnetic resonance enterography in small bowel Crohn's disease. This work makes recommendations for imaging findings that indicate small bowel Crohn's disease, how inflammatory small bowel Crohn's disease and its complications should be described, elucidates potential extra-enteric findings that may be seen at imaging, and recommends that cross-sectional enterography should be performed at diagnosis of Crohn's disease and considered for small bowel Crohn's disease monitoring paradigms. A useful morphologic construct describing how imaging findings evolve with disease progression and response is described, and standard impressions for radiologic reports that convey meaningful information to gastroenterologists and surgeons are presented.

Hypertension and estrogen deficiency in women have been identified as significant risk factors for cerebrovascular diseases. Hypertension causes excessive vascular stretch and contributes to the initiation of cellular injury in blood vessels while estrogen has been demonstrated to exert beneficial protective effects on the vascular system. Although the specific biological outcomes exerted by either excessive stretch or estrogen exposure are well established, the combined biochemical effects of both stimuli remain unclear. Therefore, this study was conducted for quantitative proteomics study on human cerebral microvascular endothelial cells (HCMECs) subjected to 20% “pathological” cyclic stretch for a period of 18 hour in the presence or absence of 17β-estradiol by isobaric Taqs for Relative and Absolute Quantification. The results showed that only some proteins responded to 17β-estradiol (e.g., thioredoxin reductase-1), stretch (e.g., 14- 3-3 protein epsilon or acidic leucine-rich nuclear phosphoprotein 32 family member B) and interestingly, some proteins returned to control pre-treatment levels when exposed to both (e.g., d-dopachrome decarboxylase, thrombospondin-1). In addition, HCMECs that exposed only to estrogen had a very similar proteomic profile (i.e., up-regulation of structural, cellular adhesion and proliferation proteins) as to those exposed to estrogen with 20% stretching for 18 hour, suggesting that estrogen ablated the detrimental effects by the stretch alone. These findings sheds light on the molecular mechanisms by which the cerebrovascular protective actions of estrogen on HCMEC exposed to pathological levels of cyclic stretch which could provide a platform for future research in therapeutic approach. DOI : http://dx.doi.org./10.17576/JSKM-2018-09

Background Postoperative Crohn’s disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging in post-operative CD surveillance is less clear. We aimed to evaluate radiographic characteristics, endoscopic concordance, and the predictive ability of imaging for postoperative recurrence (POR). Methods Multi-institution retrospective cohort study of adult CD patients who underwent ileocolonic resection (ICR) between 2009–2020. Patients with a CT or MR enterography within 90 days of a postoperative surveillance colonoscopy were included. Imaging studies were interpreted by blinded expert CD radiologists. Endoscopic activity was assessed by Rutgeerts’ scoring (POR ≥ i2b). Patients were categorized by presence of endoscopic POR (E+ or E-) or radiographic disease activity (R+ or R-) and grouped by endoscopic and radiographic concordance. Results 201 CD patients (57.7% female, mean age 31 years, 81.2% stricturing CD, 17.9% >1 prior ICR, 22.5%) with paired colonoscopy and imaging were included. Median time from ICR to paired endoscopy was 23.2 months. Imaging was highly sensitive for detecting POR (84.2%), but poorly specific (32.8%). The plurality (41.8%, N=84) were discordant E-/R+, 32.8% concordant positive (E+/R+), 20.4% concordant negative (E-/R-), and 5% discordant E+/R-. In patients with endoscopic POR, imaging detected intestinal wall thickening (86.8%; p=0.004) and hyper-enhancement (84.2%; p=0.003) at higher rates and corresponded with endoscopic severity (Figure 1). Multiple correspondence analysis showed association between severe endoscopic (i3/i4) disease and advanced radiographic disease. The majority (58.3 %) of E+/R- patients (N=12) had a Rutgeerts’ score of i2b. Majority of E-/R+ (N=84) had minimal/mild radiographic disease (81%). Differences in characteristics between the E-/R+ and E+/R+ was most pronounced in length of disease >10 cm (26.1%, 45.3%). Subsequent colonoscopies were performed in 74 E-/R+ (i0=28, i1=12, i2a=34) and 35 E-/R- (i0=20, i1=9, i2a=6) patients with 18 E-/R+ (24.3%; i0=8, i1=3, i2a=7) and 4 E-/R- (11.4%; i0=1, i1=2, i2a=1) patients developing POR (p=0.09). However, survival analysis between E-/R+ and E-/R- showed no difference to time to subsequent POR (p=0.24) (Figure 2). Imaging features at time of paired negative endoscopy did not predict subsequent endoscopic POR. Conclusion Cross-sectional imaging is highly sensitive to detect endoscopic POR; advanced radiographic disease correlates with increased endoscopic severity. Patients with no endoscopic recurrence in the presence of radiographic activity may require increased surveillance, though larger study cohorts are needed. Imaging compliments, but should not supplant, endoscopic POR surveillance paradigms.

Background Ileal pouch-anal anastomosis (IPAA) is a technically demanding procedure. Intraoperatively, great care must be taken to assure a straight superior mesenteric axis. Rarely, twisted pouches are inadvertently constructed, resulting in deviations of expected pouch function, i.e. patients readily able to open their bowels on average 7x/24 hours without pain. Twisted pouches may result in symptoms classified as pouch dysfunction. Herein we describe our quaternary pouch referral center experience with twisted pouch syndrome (TPS). Methods We performed a retrospective review of our prospectively maintained pouch registry from 1995 – 2020. Patients were identified using free-text search of redo IPAA operative reports for variations of the term “twist”. We defined twisted pouch syndrome as intraoperative findings of twisting of the pouch as the primary pathology. Data are presented as frequency (proportion) or median (interquartile range). Results Over 25-years, we identified 29 patients with confirmed TPS who underwent a redo pouch procedure by 10 surgeons. Overall, 65% were female, median BMI 21.2 (19.5 – 26) kg/m2. The duration from the index IPAA to the redo procedure was 4 (2 – 8) years; all (100%) were referral cases constructed elsewhere. Original diagnoses included: ulcerative colitis (90%), FAP (10%), lack of interstitial cells of Cajal in 1 patient (10%). All patients presented with symptoms of pouch dysfunction including erratic bowel habits (96%) with urgency/frequency, abdominal/pelvic/rectal pain (92%), and obstructive symptoms (88%). Most had (75%) been treated for chronic pouchitis with antibiotics or biologics, and 46% had undergone 1 or more additional surgery. Prior to redo IPAA procedure patients underwent a thorough workup: 100% pouchoscopy, 96% GGE, 93% underwent EUA, 88% MRI, 73% manometry, and 42% defecography. TPS was diagnosed in 15% by pouchoscopy, in 10% by imaging, and in 75% was diagnosed intra-operatively at re-diversion (20%) or revision/redo IPAA (55%). In terms of surgical intervention, 85% were initially re-diverted. A total of 18 (62%) underwent pouch revision, and 10 (38%) required redo-IPAA. Short-term outcomes: LOS 7.5 (5 – 9) days, any complication 48%, readmission 11%, reoperation 3.4%, zero mortalities. After a median follow-up 50 (28 – 60) months, 2 never had loop ileostomy closure, 1 had pouch excision, and 1 a Kock pouch, yielding an overall pouch survival rate of 86%. Conclusions Twisted pouch syndrome presents with pouch dysfunction manifest by erratic bowel habits, unexplained pain, and obstructive (defecation) symptoms. This syndrome may also mimic chronic pouchitis. Despite a thorough workup which may suggest a mechanical problem, many patient may not be diagnosed until time of redo pouch surgery. Redo surgery for twisted pouch syndrome results in long-term pouch survival for the majority.

During the early period of the COVID-19 pandemic there was a substantial decrease in pediatric emergency department (PED) visitation. The intent of this study is to report PED utilization during the COVID-19 pandemic in an urban pediatric referral center located close to the epicenter in the northeastern US.A retrospective analysis of medical records of patients visiting the PED at Robert Wood Johnson University Hospital (RWJUH) was performed. Data included: daily census, admission rate, Emergency Severity Index, and ICD-10 diagnosis codes for the period of February through July, 2018 to 2020.By the week of March 26th, visits had decreased by 70% compared to the average of the previous 2 years. This census nadir lasted for 6 weeks. At 5 weeks postnadir the average daily census recovered to levels 40% lower than prior year norms and remained at that level during subsequent months. The greatest decreases were seen in low-acuity visits. Visits for behavioral health and fractures decreased by approximately 50% and 70%, respectively, but recovered to prior year norms by June and July of 2020. Visits for asthma exacerbation decreased by as much as 87% and remained at record lows for the remainder of the study period.A substantial and persistent decrease in PED visitation was experienced during the COVID-19 pandemic. Whereas visits for behavioral health and fractures have recovered to prior year norms, visits for asthma exacerbation remain at record lows. Further research is needed to ascertain the causes of these changes, including patient perceptions of the PED.

In this article, we review the information that radiologists need to know regarding the endoscopic approach to the diagnosis and management of pancreatic cancer. This includes a review of the indications, techniques, and complications of endoscopic ultrasound. We also review information regarding endoscopic retrograde cholangiopancreatography, including the various biliary drainage techniques and the use of endoscopic palliation for patients with pancreatic cancer.

The ACR Incidental Findings Committee (IFC) presents recommendations for managing pancreatic cysts that are incidentally detected on CT or MRI. These recommendations represent an update from the pancreatic component of the JACR 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. The Pancreas Subcommittee—which included abdominal radiologists, a gastroenterologist, and a pancreatic surgeon—developed this algorithm. The recommendations draw from published evidence and expert opinion, and were finalized by informal iterative consensus. Algorithm branches successively categorize pancreatic cysts based on patient characteristics and imaging features. They terminate with an ascertainment of benignity and/or indolence (sufficient to discontinue follow-up), or a management recommendation. The algorithm addresses most, but not all, pathologies and clinical scenarios. Our goal is to improve quality of care by providing guidance on how to manage incidentally detected pancreatic cysts.

The clinical scenario of a woman aged 30–50 years presenting with progressive lower limb spasticity, asymmetric changes on visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs) consistent with central demyelination would commonly indicate primary progressive multiple sclerosis (PPMS).

Necrosis significantly increases rates of morbidity and mortality in acute pancreatitis. Hospitalists and general internists are on the front lines in identifying severe cases and consulting the appropriate specialists for optimal multidisciplinary care.

Introduction One approach to slow the pandemic of obesity and chronic disease is to look to our evolutionary past for clues of the changing behaviors contributing to the emergence of 'diseases of civilization'. Modern humans have deviated from the lifestyle behaviors of our ancestors that have introduced pressures (i.e. diet and activity changes) quicker than our genetic ability to respond. This caused a 'mismatch' between our biological systems and environment, leading to 'man-made' chronic diseases. Purpose The purpose of the study was to investigate the effects of a short-term evolutionarily informed dietary and lifestyle intervention on inflammatory and cardio-metabolic profiles in individuals characterized as having metabolic syndrome (MetS). Methods Twelve subjects with MetS followed a crossover design with two, four-week interventions, including a carbohydrate (CHO)-restricted Paleolithic-based diet (CRPD

Introduction Metabolic syndrome (MetS) has been recognized as one of the most important clinical challenges and global health issues of today. Growing evidence suggests that mechanisms of energy metabolism may also play a key role in mediating aspects of cognitive function. Brain-derived neurotrophic factor (BDNF) is one such factor well known for its critical role in neuronal plasticity, including memory and learning, and more recently metabolic processes. BDNF levels have been shown separately to be dependent on diet and exercise programming. Purpose The purpose of this study was to investigate the effect of diet and exercise on BDNF levels and cognitive functioning with any metabolic association in individuals characterized with MetS. Methods Twelve subjects with MetS followed a randomized crossover design with two four-week interventions, including a carbohydrate (CHO)-restricted Paleolithic-based diet (CRPD

Background One of the most significant challenges in colorectal cancer (CRC) management is the use of compliant early stage population-based diagnostic tests as adjuncts to confirmatory colonoscopy. Despite the near curative nature of early clinical stage surgical resection, mortality remains unacceptably high—as the majority of patients diagnosed by faecal haemoglobin followed by colonoscopy occur at latter stages. Additionally, current population-based screens reliant on fecal occult blood test (FOBT) have low compliance (~ 40%) and tests suffer low sensitivities. Therefore, blood-based diagnostic tests offer survival benefits from their higher compliance (≥ 97%), if they can at least match the sensitivity and specificity of FOBTs. However, discovery of low abundance plasma biomarkers is difficult due to occupancy of a high percentage of proteomic discovery space by many high abundance plasma proteins (e.g., human serum albumin). Methods A combination of high abundance protein ultradepletion (e.g., MARS-14 and an in-house IgY depletion columns) strategies, extensive peptide fractionation methods (SCX, SAX, High pH and SEC) and SWATH-MS were utilized to uncover protein biomarkers from a cohort of 100 plasma samples (i.e., pools of 20 healthy and 20 stages I–IV CRC plasmas). The differentially expressed proteins were analyzed using ANOVA and pairwise t-tests (p 1.5), and further examined with a neural network classification method using in silico augmented 5000 patient datasets. Results Ultradepletion combined with peptide fractionation allowed for the identification of a total of 513 plasma proteins, 8 of which had not been previously reported in human plasma (based on PeptideAtlas database). SWATH-MS analysis revealed 37 protein biomarker candidates that exhibited differential expression across CRC stages compared to healthy controls. Of those, 7 candidates (CST3, GPX3, CFD, MRC1, COMP, PON1 and ADAMDEC1) were validated using Western blotting and/or ELISA. The neural network classification narrowed down candidate biomarkers to 5 proteins (SAA2, APCS, APOA4, F2 and AMBP) that had maintained accuracy which could discern early (I/II) from late (III/IV) stage CRC. Conclusion MS-based proteomics in combination with ultradepletion strategies have an immense potential of identifying diagnostic protein biosignature.

Background Electromyogram (EMG) burst duration can provide additional diagnostic information when investigating hyperkinetic movement disorders, particularly when a functional movement disorder is suspected. It is generally accepted that EMG bursts

Background Physicians can come across patients who are exposed to certain prescription drugs or toxins that can result in adverse effects and complications which have high rates of morbidity and mortality. Objective To summarise the key clinical features and management of the common movement disorder toxidromes relevant to physicians (with an interest in neurology). Methods We searched PUBMED from 1946 to 2016 for papers relating to movement toxidromes and their treatment. The findings from those studies were then summarised and are presented here. Results The key features of 6 of the common movement disorder toxidromes and their treatment are tabulated and highlighted. The management of toxidromes with the highest mortality like neuroleptic malignant syndrome and serotonin syndrome are discussed in detail. Conclusion There are several toxidromes that have the potential to become a serious life-threatening emergency if there is a delay in recognition of key clinical features and instituting the appropriate treatment at the earliest is crucial.

Dementia is a global health problem with a huge impact on the lives of those afflicted. There are several distinct diseases that are classified under the umbrella term "dementia" ranging from neurodegenerative disorders such as Alzheimer's disease to chronic infections of the central nervous system such as subacute sclerosing panencephalitis (SSPE), a rare complication of measles virus infection in childhood. Clinical features, neuropsychological profiles and imaging characteristics of the various dementia syndromes can be sufficiently distinct to distinguish them from one another. However, in some cases, the cognitive, psychiatric and behavioural features can sufficiently overlap such that neurophysiologic testing may be of help. While it is recognized the electroencephalogram (EEG) may have a special role to play in the diagnosis of certain dementing illnesses such as SSPE and Creutzfeldt-Jakob disease (CJD) that have characteristic EEG changes, current research focusses on the potential utility of quantitative EEG as one more tool in the armamentarium of clinicians dealing with patients who suffer from a dementing illness. We searched PubMed and the Cochrane Database from 1 January 1946 up to 1 January 2016, combining the search terms "EEG," "electroencephalography," "dementia" and "status epilepticus"; identified papers from these searches were then read in detail and summarized. Here, we discuss both the qualitative and quantitative EEG findings in the various types of dementia.

SummaryThe gut microbiota plays a key role in host metabolism. Toll-like receptor 5 (TLR5), a flagellin receptor, is required for gut microbiota homeostasis. Accordingly, TLR5-deficient (T5KO) mice are prone to develop microbiota-dependent metabolic syndrome. Here we observed that T5KO mice display elevated neutral lipids with a compositional increase of oleate [C18:1 (n9)] relative to wild-type littermates. Increased oleate contribution to hepatic lipids and liver SCD1 expression were both microbiota dependent. Analysis of short-chain fatty acids (SCFAs) and 13C-acetate label incorporation revealed elevated SCFA in ceca and hepatic portal blood and increased liver de novo lipogenesis in T5KO mice. Dietary SCFAs further aggravated metabolic syndrome in T5KO mice. Deletion of hepatic SCD1 not only prevented hepatic neutral lipid oleate enrichment but also ameliorated metabolic syndrome in T5KO mice. Collectively, these results underscore the key role of the gut microbiota-liver axis in the pathogenesis of metabolic diseases.

Computed tomography enterography and magnetic resonance enterography are essential in the evaluation and treatment of patients with Crohn's disease. As such, examination reporting must use standardized nomenclature for effective communication. This report documents an interdisciplinary consensus of the Society of Abdominal Radiology, the Society of Pediatric Radiology, and the American Gastroenterology Association on the computed tomography enterography/magnetic resonance enterography imaging findings and imaging-based morphologic phenotypes.

BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti‐fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti‐fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre‐stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naive small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post‐prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24‐48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.

Infectious and inflammatory enterocolitides can present with an acute abdomen. The most common entities are ulcerative colitis, Crohn disease, and Clostridium difficile colitis. This article reviews the clinical and imaging findings of patients who present acutely with infectious and inflammatory enterocolitides. The acute abdomen can be defined as the sudden onset (generally