Cortical networks are disturbed in people with cirrhosis even in the absence of neuropsychometric impairment

OBJECTIVE: Hepatic encephalopathy is a common complication of cirrhosis; it is characterised by neuropsychometric/neurophysiological abnormalities. Its pathophysiology is complex but glial neuronal communication is likely to be disrupted and to impact on oscillatory networks and cortical connectivity. The aim of this study was to use multichannel electroencephalography (EEG) to investigate functional connectivity, as a surrogate for cortical networks, in patients with cirrhosis. METHODS: Resting EEGs were recorded in 98 healthy controls and in 264 patients with cirrhosis characterised psychometrically using the Psychometric Hepatic Encephalopathy Score (PHES). Functional connectivity was calculated using the phase-lag index with stratification into standard EEG frequency bands. The findings were validated in a further cohort of 39 healthy controls and 106 patients with cirrhosis. RESULTS: Widespread disruption in functional connectivity was observed in the patients compared with the controls; connectivity was increased in the theta (4-8 Hz) band and decreased in the delta (1-3.5 Hz), alpha (8.5-13 Hz) and beta (13.5-26.5 Hz) bands. Changes were apparent even in patients who were psychometrically unimpaired compared with healthy controls viz mean ± SEM theta 0.107 ± 0.001 vs. 0.103 ± 0.002 (p < 0.05) and alpha 0.139 ± 0.003 vs. 0.154 ± 0.003 (p < 0.01); more pronounced changes were observed with increasing neuropsychometric impairment. The findings were replicated in the second cohort. CONCLUSIONS: Cortical networks are disturbed in patients with cirrhosis even in the absence of psychometric impairment. SIGNIFICANCE: These findings will facilitate further exploration of the pathophysiology of this condition and provide a robust means for assessing treatment effects in research settings

Modular, Distributed Spatial Metadata Repository on the Services Principle

Despite major improvements in GIS technologies in recent years, it remains particularly difficult to efficiently locate geospatial data. Purdue Libraries, in keeping with their efforts to build a distributed, cross-discipline data repository, is nearing an alpha release of a metadata portal through which large amounts of base data as well as Purdue-produced geospatial data can be located, downloaded or connected to. GIS Librarian Miller will discuss the project and how it might interact with existing campus systems

Pharmacological pain management in chronic pancreatitis

Contains fulltext : 125762.pdf (publisher's version ) (Open Access)Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders. An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established, the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive. Consequently, the management of pain by traditional methods based on nociceptive deafferentation (e.g., surgery and visceral nerve blockade) becomes difficult and often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source, which should be reserved for special and carefully selected cases. In this review, we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis. In addition, future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity

Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis

Contains fulltext : 117527.pdf (publisher's version ) (Open Access)BACKGROUND: A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. METHODS: Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. RESULTS: The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (PaeuroS=aeuroS0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (PaeuroS=aeuroS0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. CONCLUSIONS: The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine