Classifications of seizures and epilepsies, where are we? - A brief historical review and update.

In March 2017, the International League Against Epilepsy (ILAE) announced their new classifications of seizures and epilepsies. Development of these classification systems led by the ILAE is a long and complicated process. Outsiders may find it difficult to understand the arguments behind. We summarize the major developmental milestones of the ILAE classification schemata. An update of the latest classification is also included. It is hope that this review can serve as an outline in learning the taxonomy in epileptology.

Poor predictive value of breath hydrogen response for probiotic effects in IBS.

BACKGROUND AND AIMS: Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics. METHODS: In a randomized, double-blind, placebo-controlled trial, patients with IBS (Rome III) were randomized to either 65 mL/day fermented milk product containing probiotic (FMPP) or placebo for 6 weeks, followed by 6 weeks' open-label treatment and 6 weeks' withdrawal. Breath hydrogen responses to lactulose (15 g) and liquid-gastric emptying time were evaluated before and at the end of each treatment period. Symptoms were measured using a 100-mm visual analog scale. RESULTS: Loss of ERBHAL occurred in 36% of 23 patients receiving FMPP and 41% of 22 receiving placebo (P = 1.00). Amongst 40 patients who completed open-label FMPP treatment, ERBHAL was lost in a further 38%, continued in 25%, and regained in 10%. Similar variability occurred in the withdrawal phase. Variability was unrelated to changes in gastric emptying. No differences in symptom response were seen between treatment groups nor in relation to the loss or retention of ERBHAL. CONCLUSIONS: Breath hydrogen patterns after lactulose are poorly reproducible. No FMPP-specific effects on fermentation patterns or symptoms were observed. The presence of ERBHAL is not useful to predict symptomatic response to probiotic therapy in patients with IBS.

Venous and arterial disease in inflammatory bowel disease.

Awareness is increasing that risk of venous thromboembolism and development of atherosclerosis is elevated in patients with some chronic inflammatory diseases. This review aimed to examine the risk of vascular disease in patients with inflammatory bowel disease (IBD) and to identify potential pathogenic mechanisms and therapeutic approaches. An extensive literature search was conducted using MEDLINE database, Cochrane Library and international conference abstracts for studies pertaining to venous and arterial thromboembolism in adult IBD patients. There is a 1.1-3.6 fold risk of venothromboembolism in IBD, affecting 0.55-6.15% of patients. Risks are increased during a flare or with chronically active inflammation. Evidence is building that there may be a modestly increased risk of arterial disease overall, despite evidence that traditional risk factors may be reduced. Multiple pathogenic factors have been identified including endothelial dysfunction, inflammation-mediated calcium deposition in the media of arteries, hyperhomocysteinemia, platelet activation, and altered coagulation and fibrinolysis. The key to active and preventive therapy is to effectively treat inflammation. Recommendations for prophylaxis of venothromboembolism have followed guidelines where they exist and have been extrapolated from studies of other at-risk conditions, as have those for arterial disease, where screening for risk factors and actively treating abnormalities is encouraged. In conclusion, patients with IBD are at considerably increased risk of venothromboembolism and probably of arterial disease, in particular mesenteric ischemia and ischemic heart disease. Increased penetration of gaps between this knowledge and clinical therapeutic action to prevent thromboembolic events into IBD clinical practice is needed.

Genetic determination of regional connectivity in modelling the spread of COVID-19 outbreak for more efficient mitigation strategies.

For the COVID-19 pandemic, viral transmission has been documented in many historical and geographical contexts. Nevertheless, few studies have explicitly modeled the spatiotemporal flow based on genetic sequences, to develop mitigation strategies. Additionally, thousands of SARS-CoV-2 genomes have been sequenced with associated records, potentially providing a rich source for such spatiotemporal analysis, an unprecedented amount during a single outbreak. Here, in a case study of seven states, we model the first wave of the outbreak by determining regional connectivity from phylogenetic sequence information (i.e. "genetic connectivity"), in addition to traditional epidemiologic and demographic parameters. Our study shows nearly all of the initial outbreak can be traced to a few lineages, rather than disconnected outbreaks, indicative of a mostly continuous initial viral flow. While the geographic distance from hotspots is initially important in the modeling, genetic connectivity becomes increasingly significant later in the first wave. Moreover, our model predicts that isolated local strategies (e.g. relying on herd immunity) can negatively impact neighboring regions, suggesting more efficient mitigation is possible with unified, cross-border interventions. Finally, our results suggest that a few targeted interventions based on connectivity can have an effect similar to that of an overall lockdown. They also suggest that while successful lockdowns are very effective in mitigating an outbreak, less disciplined lockdowns quickly decrease in effectiveness. Our study provides a framework for combining phylodynamic and computational methods to identify targeted interventions.

Patchy colitis, and young age at diagnosis and at the time of surgery predict subsequent development of Crohn's disease after ileal pouch-anal anastomosis surgery for ulcerative colitis.

BACKGROUND AND AIM: A proportion of patients having total proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) are later diagnosed with Crohn's disease (CD). The aim of this study was to identify preoperative and perioperative predictors for the subsequent development of CD in patients who had IPAA for presumed UC. METHODS: A retrospective case-control study of patients undergoing IPAA surgery for presumed UC was undertaken. Cases were patients who had a revised diagnosis of CD after surgery. Preoperative and perioperative variables were examined and analyzed. RESULTS: Fifteen cases were compared with 39 controls. Patients aged ≤25 years at initial UC diagnosis were more likely to develop CD compared to those aged >25 years (odds ratio, OR [95% confidence interval, CI]: 7.1 [1.6-31.3]; P = 0.01). Patients aged ≤30 years at the time of colectomy had an increased risk of subsequent development of CD compared to those aged >30 years (OR [95% CI]: 4.5 [1.3-16.0]; P = 0.02). Cases were more likely to have patchy colitis on their colectomy specimen (OR [95% CI]: 6.7 [1.1-41.8]; P = 0.04). There was no significant difference between groups regarding transmural inflammation, ileitis, or fissuring ulcers on colectomy specimens, or preoperative C-reactive protein (CRP), albumin, family history, and smoking status. CONCLUSION: Predictors of the development of CD in the pouch include young age at diagnosis and at the time of surgery, and patchy colitis in the resected colon.

Entyvio lengthen dose-interval study: lengthening vedolizumab dose interval and the risk of clinical relapse in inflammatory bowel disease.

BACKGROUND: Vedolizumab (VDZ), an α4ß7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously. AIM: To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing. MATERIALS AND METHODS: This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected. RESULTS: There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size. CONCLUSION: The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.

Deletion of p22phox-dependent oxidative stress in the hypothalamus protects against obesity by modulating ß3-adrenergic mechanisms.

A role for oxidative stress in the brain has been suggested in the pathogenesis of diet-induced obesity (DIO), although the underlying neural regions and mechanisms remain incompletely defined. We tested the hypothesis that NADPH oxidase-dependent oxidative stress in the paraventricular nucleus (PVN), a hypothalamic energy homeostasis center, contributes to the development of DIO. Cre/LoxP technology was coupled with selective PVN adenoviral microinjection to ablate p22phox , the obligatory subunit for NADPH oxidase activity, in mice harboring a conditional p22phox allele. Selective deletion of p22phox in the PVN protected mice from high-fat DIO independent of changes in food intake or locomotor activity. This was accompanied by ß3-adrenoceptor-dependent increases in energy expenditure, elevations in brown adipose tissue thermogenesis, and browning of white adipose tissue. These data reveal a potentially novel role for brain oxidative stress in the development of DIO by modulating ß3-adrenoceptor mechanisms and point to the PVN as an underlying neural site.