Reetta Kivisaari

Enhancement of GABA-related signalling is associated with increase of functional connectivity in human cortex

Structural or operational synchrony analysis with EEG was conducted in order to detect functional interaction between cortical areas during an enhanced inhibition induced by the GABAergic agonist lorazepam in a double‐blind, randomized, placebo‐controlled, cross‐over study in eight healthy human subjects. Specifically, we investigated whether a neuronal inhibitory system in the brain mediates functional decoupling of cortical areas. Single‐dose lorazepam administration resulted in a widespread increase in the inter‐area functional connectivity and an increase in the strength of functional long‐range and interhemispheric connections. These results suggest that inhibition can be an efficient mechanism for synchronization of large neuronal populations. Hum. Brain Mapping 22:29–41, 2004.

The interplay of lorazepam-induced brain oscillations: microstructural electromagnetic study

OBJECTIVEnThe effects on cortical rhythms of a single-dose (30 microg/kg) administration of the GABAA agonist lorazepam were examined in a randomized, double-blind, cross-over, placebo-controlled study with 8 healthy volunteers using simultaneous electroencephalography (EEG) and magnetoencephalography (MEG).nnnMETHODSnThe oscillations were assessed by means of adaptive classification of short-term spectral patterns.nnnRESULTSnLorazepam (a) decreased the percentage of EEG/MEG segments with fast-theta, delta-alpha, fast-theta-alpha and alpha activity and increased percentage of EEG/MEG segments with delta, delta-slow-theta, delta-beta, slow-theta and polyrhythmic activity; (b) decreased diversity of EEG/MEG signals (in terms of spectral patterns) and increased the general instability of the signal; (c) increased stabilization periods of the spectral patterns (reduced brain information processing); (d) maintained larger maximum periods of temporal stabilization for delta, slow-theta, delta-slow-theta, delta-beta and polyrhythmic activity (in terms of spectral patterns); (e) did not increase power in the independent beta rhythm.nnnCONCLUSIONSnLorazepam caused significant reorganization of the EEG/MEG microstructure. These results suggest also that adaptive classification analysis of single short-term spectral patterns may provide additional information to conventional spectral analyses.

Modulation of somatosensory evoked fields from SI and SII by acute GABA A-agonism and paired-pulse stimulation.

The purpose of the present study was to shed light on the physiology underlying somatosensory evoked magnetic fields (SEFs) by means of pharmacological manipulation with the GABA A agonist lorazepam and paired-pulse stimulation. SEFs were recorded from the primary (SI) and secondary (SII) somatosensory cortices following median nerve stimulation. Responses were obtained to single stimuli every 2 s and to paired stimuli with interpulse intervals (IPIs) of 20 ms and 100 ms. Recordings were performed in 2 sessions, once after the intravenous injection of lorazepam and once after the injection of placebo. The underlying neural generators of the response components were modelled with single equivalent current dipoles (ECDs). In the single-stimulus condition, lorazepam slightly increased the ECD strength of the 1st excitatory deflection (N20m) from the contralateral SI and reduced the strengths of the following P35m, P60m and N140m deflections from the contralateral SI and the response from the ipsilateral SII. Under placebo, paired-pulse stimulation with the IPI of 20 ms diminished all SEF components compared with single-pulse stimulation. At the IPI of 100 ms, the N20m and the P60m deflections from SI had recovered to nearly baseline levels, being consistent with recovery cycles of excitatory postsynaptic potentials (EPSPs). In contrast, the P35m and N140m, as well as the SII deflections, did not recover at 100 ms. Lorazepam had no effect on the paired-pulse depression (PPD) or recovery thereof for the N20m deflection. The attenuation of the P35m deflection by lorazepam and its lack of recovery in the 100-ms paired-pulse condition are expected behaviours of inhibitory postsynaptic potentials (IPSPs) in intracellular recordings, thus lending further support to our previous suggestion that P35m largely represents IPSPs. The lack of PPD modulation of N20m by lorazepam suggests that paired-pulse depression of the first cortical excitatory response (N20m) may be caused by mechanisms other than GABA A receptor-mediated inhibition.

Small Bowel Dilatation Predicts Prolonged Parenteral Nutrition and Decreased Survival in Pediatric Short Bowel Syndrome.

Objective: To analyze risk factors and prognostic significance of small bowel (SB) dilatation in children with short bowel syndrome (SBS). Background: In SBS, the remaining SB may dilate as part of intestinal adaptation. The impact of dilatation on parenteral nutrition (PN) dependence and survival has not been studied systematically. Methods: SB diameter of SBS children (n = 61) was measured in contrast SB series (n = 169, median age 0.94, range 0.32–2.7 years) during 2002 to 2015, and expressed as millimeters (SB width) and as ratio to L5 vertebra height (SB diameter ratio). Linear regression was used to examine risk factors for dilatation. PN weaning and survival were analyzed with Cox proportional hazards regression. Results: Maximal SB diameter ratio during follow-up was predicted by PN dependence and SB atresia, while maximal absolute SB width by birth weight, age, PN duration, and remaining bowel length. Weaning off PN was 14-fold more likely in patients with maximal SB diameter ratio <2.00 compared with >3.00 (P = 0.005), and 5.4-fold more likely when maximal SB width was <20u200amm compared with >30u200amm (P = 0.023). After adjustment for age, remaining SB length, and the presence of ileocecal valve, both estimates of maximal SB dilatation remained significant independent predictors for weaning off PN. When all measurements were included, the cumulative survival was worse if SB diameter ratio exceeded 2.00 (P = 0.002–0.042). Conclusions: SB dilatation predicts prolonged PN duration and decreased survival in SBS children. Measurement of maximal SB diameter standardized to L5 vertebra height may be a valuable objective tool for patient follow-up and assessment of prognosis.

Spinal cord anomalies in patients with anorectal malformations without severe sacral abnormalities or meningomyelocele: outcomes after expectant, conservative management

OBJECTIVE The goal of this study was to determine the significance of spinal cord anomalies (SCAs) in patients with anorectal malformations (ARMs) by comparing the outcomes for bowel function, lower urinary tract symptoms (LUTS), and lower-limb neurological abnormalities to these outcomes in patients with similar ARMs and a normal spinal cord. METHODS The spinal cord MRI records of female patients treated for vestibular and perineal fistula (VF/PF) and male patients with rectourethral fistula (RUF) at a single center between 1983 and 2006 were reviewed. Bowel function and LUTS were assessed by questionnaire. Patients with extensive sacral anomalies or meningomyelocele were excluded. RESULTS Of 89 patients (median age 15 years, range 5-29 years), MRI was available in 90% (n = 80; 40 male patients with RUF), and 80% of patients returned the questionnaire (n = 64; 31 male patients with RUF). Spinal cord anomalies were found in 34%, comprising a filum terminale lipoma in 30%, low conus medullaris in 10%, and thoracolumbar syrinx in 6%. Bowel functional outcomes between patients with SCAs (n = 23) and those with a normal spinal cord (n = 41) were not significantly different for soiling (70% vs 63%), fecal accidents (43% vs 34%), and constipation (57% vs 39%; p = not significant for all). The LUTS, including urge (65% vs 54%), urge incontinence (39% vs 24%), stress incontinence (17% vs 22%), and straining (32% vs 29%) were also comparable between groups (p = not significant for all). No patients developed lower-limb neurological abnormalities. CONCLUSIONS The results suggest that the long-term functional outcomes for patients with SCAs who had VF/PF and RUF may not differ significantly from patients with the same type of ARMs and a normal spinal cord. The results favor a conservative approach to their management in the absence of abnormal neurological findings in the lower limbs.

Transient elastography and aspartate aminotransferase to platelet ratio predict liver injury in paediatric intestinal failure.

We aimed to evaluate the value of AST to platelet ratio (APRI) and transient elastography (TE) as predictors of liver histopathology in children with intestinal failure (IF).

A Prospective Comparison of Noninvasive Methods in the Assessment of Liver Fibrosis and Esophageal Varices in Pediatric Chronic Liver Diseases.

Goals and Background: We compared liver stiffness (LS), the aspartate aminotransferase-to-platelet ratio index (APRi), and the platelet-to-spleen size z score ratio (P/SZC) in the prediction of liver fibrosis and esophageal varices in children. Study: LS, APRi, SZC, and P/SZC were prospectively determined in 99 unselected consecutive children, who underwent liver biopsy for the follow-up of chronic liver disorders. LS was assessed by transient elastography. The spleen size was evaluated as the SD from age-specific and gender-specific normative values. Varices were assessed endoscopically (n=64). Biopsies were staged according to Metavir. Results: The median patient age was 6.0 (interquartile range, 1.8 to 12.9) years. Underlying diagnoses included intestinal failure (n=31), biliary atresia (n=24), and others (n=44). LS showed the strongest correlation with the fibrosis stage (r=0.639, P<0.001) compared with P/SZC (r=−0.427, P=0.003), APRi (r=0.419, P=0.001), or SZC (r=0.396, P=0.004). LS clearly performed the best in predicting fibrosis with area under the receiver operator curve (AUROC) values of 0.789 [95% confidence interval (CI), 0.698-0.879; P<0.001] for any (Metavir≥1), and 0.831 (95% CI, 0.745-0.918; P<0.001) for significant (Metavir≥2) fibrosis. For the prediction of the presence of esophageal varices, APRi had a higher AUROC of 0.832 (95% CI, 0.730-0.934; P<0.001), when compared with LS, SZC, or P/SZC with AUROCs of 0.818 (95% CI, 0.706-0.930; P<0.001), 0.795 (95% CI, 0.683-0.904; P=0.001), and 0.760 (95% CI, 0.610-0.909; P=0.004), respectively. Conclusions: LS performed the best in predicting liver fibrosis, whereas APRi had the highest predictive accuracy for esophageal varices. An LS value over 7.7 kPa identified significant liver fibrosis with high accuracy, whereas low APRi ascertained the absence of esophageal varices.

Risk factors and outcomes of tapering surgery for small intestinal dilatation in pediatric short bowel syndrome

BACKGROUNDnIn remains unclear why in some short bowel syndrome (SBS) patients, the remaining small bowel (SB) dilates excessively leading to requirement of tapering surgery.nnnMETHODSnAmong SBS children, we retrospectively analyzed risk factors for tapering surgery with logistic regression and compared the outcome of operated patients (n=16) to those managed conservatively (n=44) with Cox proportional hazards regression.nnnRESULTSnSBS was caused by necrotizing enterocolitis (NEC) (n=31), SB atresia (SBA) (n=13), midgut volvulus (n=12), or gastroschisis (n=4). Patients with spontaneous symptomatic SB dilatation unable to wean parenteral nutrition (PN) underwent tapering surgery at median age of 1.04 (interquartile range 0.70-3.27) years. Missing ICV was related to an 8-fold (p=0.003) increased risk while SBA diagnosis was related to a 13-fold risk of tapering surgery (p<0.001). Increasing SB length and NEC diagnosis were protective of tapering (p=0.027-0.004). Of operated patients, 75% reached enteral autonomy during follow-up and their postoperative adjusted PN weaning rate was similar to nonoperated children (p=0.842).nnnCONCLUSIONnSBS children with short remaining SB, missing ICV, and SBA etiology are more likely while NEC patients are less likely than others to necessitate tapering surgery. Postoperative PN weaning rates were comparable to patients who initially had more favorable intestinal anatomy and adapted without surgery.

Segmental cystic kidney tumours in children

Abstract Objective. Segmental cystic tumours in the kidney are extremely rare in children. This study reports our experience of those tumours. Material and methods. The operative database from 1993 to 2008 of the Hospital for Children and Adolescents, University of Helsinki, was evaluated for segmental cystic renal tumours without any solid component. Patient records, imaging studies and pathology specimens were reviewed. Results. Four cases (three girls and one boy) were found; all were less than 3 years old at the time of diagnosis. All patients underwent kidney-preserving surgery with resection of the cystic tumour. Two patients had neoplasias: one cystic nephroma and one cystic partially differentiated nephroblastoma. Both of these patients had associated or predisposing disease (type I cystic pleuropulmonary blastoma of the lung and mulibrey nanism, respectively). Two patients had a non-neoplastic tumour; localized cystic disease of the kidney and segmental adult type autosomal dominant polycystic kidney disease. Neoplastic cystic tumours had a fibrous capsule in preoperative magnetic resonance imaging and also in operation, unlike non-neoplastic lesions. Conclusions. Preoperative and perioperative diagnosis is difficult in cases of segmental cystic kidney tumours in a child. If a neoplastic tumour is suspected complete resection of the tumour is mandatory.

31Phosphorus magnetic resonance spectroscopy of the liver for evaluating inflammation and fibrosis in autoimmune hepatitis

Abstract Background: Liver biopsy is the gold standard in evaluating inflammation and fibrosis in autoimmune hepatitis. Aims: In search of non-invasive follow-up tools in autoimmune hepatitis, we evaluated 31phosphorus magnetic resonance spectroscopy (31P MRS). Methods: Twelve consecutive AIH patients (mean age 42.8 years, 10 women) underwent liver biopsy, routine laboratory liver function tests, which were compared to findings in 31P MRS and transient elastography (TE). Results: Phosphoenolpuryvate (PEP) correlated with the grade of inflammation (ru2009=u20090.746, pu2009=u2009.005) and thromboplastin time (ru2009=u20090.592, pu2009=u2009.043). It also differentiated patients with active inflammation from patients without (tu2009=u20093.781, pu2009=u2009.009). There was no correlation between PEP and aminotransferase or immunoglobulin G levels. The phosphoethanolamine (PE)/phosphocholine (PC) ratio, PE/glyserophosphoethanolamine (GPE) ratio and PC/[total phosphomonoester (PME)u2009+u2009phosphodiester (PDE)] ratios correlated with immunoglobulin G (ru2009=u20090.764, pu2009=u2009.006; ru2009=u20090.618, pu2009=u2009.043; and r=u2009−0.636, pu2009=u2009.035, respectively). PME/PDE and PE/GPE correlated with fibrosis (ru2009=u20090.668, pu2009=u2009.018 and ru2009=u20090.604, pu2009=u2009.037). PE/GPE also differentiated F3 from F0-2 patients (tu2009=u20093.810, pu2009=u2009.003). Phosphorus metabolites did not correlate with TE results and TE did not correlate with liver histology or laboratory parameters. Conclusions: 31P MRS seems to detect active inflammation and advanced fibrosis in AIH patients. TE was ineffective in fibrosis quantification.