Epileptogenic Tubers Are Associated with Increased Kurtosis of Susceptibility Values: A Combined Quantitative Susceptibility Mapping and Stereoelectroencephalography Pilot Study.

BACKGROUND AND PURPOSE: Prior studies have found an association between calcification and the epileptogenicity of tubers in tuberous sclerosis complex. Quantitative susceptibility mapping is a novel tool sensitive to magnetic susceptibility alterations due to tissue calcification. We assessed the utility of quantitative susceptibility mapping in identifying putative epileptogenic tubers in tuberous sclerosis complex using stereoelectroencephalography data as ground truth. MATERIALS AND METHODS: We studied patients with tuberous sclerosis complex undergoing stereoelectroencephalography at a single center who had multiecho gradient-echo sequences available. Quantitative susceptibility mapping and R2* values were extracted for all tubers on the basis of manually drawn 3D ROIs using T1- and T2-FLAIR sequences. Characteristics of quantitative susceptibility mapping and R2* distributions from implanted tubers were compared using binary logistic generalized estimating equation models designed to identify ictal (involved in seizure onset) and interictal (persistent interictal epileptiform activity) tubers. These models were then applied to the unimplanted tubers to identify potential ictal and interictal tubers that were not sampled by stereoelectroencephalography. RESULTS: A total of 146 tubers were identified in 10 patients, 76 of which were sampled using stereoelectroencephalography. Increased kurtosis of the tuber quantitative susceptibility mapping values was associated with epileptogenicity (P = .04 for the ictal group and P = .005 for the interictal group) by the generalized estimating equation model. Both groups had poor sensitivity (35.0% and 44.1%, respectively) but high specificity (94.6% and 78.6%, respectively). CONCLUSIONS: Our finding of increased kurtosis of quantitative susceptibility mapping values (heavy-tailed distribution) was highly specific, suggesting that it may be a useful biomarker to identify putative epileptogenic tubers in tuberous sclerosis complex. This finding motivates the investigation of underlying tuber mineralization and other properties driving kurtosis changes in quantitative susceptibility mapping values.

Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery.

BACKGROUND AND PURPOSE: Pediatric posterior fossa tumors often present with hydrocephalus; postoperatively, up to 25% of patients develop cerebellar mutism syndrome. Arterial spin-labeling is a noninvasive means of quantifying CBF and bolus arrival time. The aim of this study was to investigate how changes in perfusion metrics in children with posterior fossa tumors are modulated by cerebellar mutism syndrome and hydrocephalus requiring pre-resection CSF diversion. MATERIALS AND METHODS: Forty-four patients were prospectively scanned at 3 time points (preoperatively, postoperatively, and at 3-month follow-up) with single- and multi-inflow time arterial spin-labeling sequences. Regional analyses of CBF and bolus arrival time were conducted using coregistered anatomic parcellations. ANOVA and multivariable, linear mixed-effects modeling analysis approaches were used. The study was registered at clinicaltrials.gov (NCT03471026). RESULTS: CBF increased after tumor resection and at follow-up scanning (P = .045). Bolus arrival time decreased after tumor resection and at follow-up scanning (P = .018). Bolus arrival time was prolonged (P = .058) following the midline approach, compared with cerebellar hemispheric surgical approaches to posterior fossa tumors. Multivariable linear mixed-effects modeling showed that regional perfusion changes were more pronounced in the 6 children who presented with symptomatic obstructive hydrocephalus requiring pre-resection CSF diversion, with hydrocephalus lowering the baseline mean CBF by 20.5 (standard error, 6.27) mL/100g/min. Children diagnosed with cerebellar mutism syndrome (8/44, 18.2%) had significantly higher CBF at follow-up imaging than those who were not (P = .040), but no differences in pre- or postoperative perfusion parameters were seen. CONCLUSIONS: Multi-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following resolution of cerebellar mutism syndrome.

High incidence and treatment of flexor carpi radialis tendinitis after trapeziectomy and abductor pollicis longus suspensionplasty for basal joint arthritis.

We reviewed the incidence and treatment of flexor carpi radialis tendinitis in 77 patients (81 thumbs) who had trapeziectomy and abductor pollicis longus suspensionplasty for thumb carpometacarpal joint arthritis. Eighteen patients, 20 wrists (25%) had flexor carpi radialis tendinitis. The onset was 2-10 months (mean 4.7) after surgery. Two cases had preceding trauma. Eight cases (40%) responded to splinting and steroid injection. Ten patients, 12 wrists (60%) underwent surgery after failing non-operative treatment. Eleven wrists had frayed or partially torn flexor carpi radialis tendon and one had a complete tendon rupture with pseudotendon formation. Flexor carpi radialis tenotomy and pseudotendon excision were performed. All operated patients obtained good pain relief initially post-operatively. However, the pain recurred in two patients after 8 months. One required a local steroid injection for localized tenderness at the site of the proximal tendon stump. The other patient required a revision operation for scaphotrapezoid impingement. Both obtained complete pain relief. Our study has shown a high incidence of flexor carpi radialis tendinitis following trapeziectomy and abductor pollicis longus suspensionplasty. Patients should be warned about this potential complication.

Integrated approach for the study of anatomical variability in the cardiac Purkinje system: from high resolution MRI to electrophysiology simulation.

The ordered electrical stimulation of the ventricles is achieved by a specialized network of fibres known as the Purkinje system. The gross anatomy and basic functional role of the Purkinje system is well understood. However, very little is known about the detailed anatomy of the Purkinje system, its inter-individual variability and the implications of the variability in ventricular function, in part due to limitations in experimental techniques. In this study, we aim to provide new insight into the inter-individual variability of the free running Purkinje system anatomy and its impact on ventricular electrophysiological function. As a first step towards achieving this aim, high resolution magnetic resonance imaging (MRI) datasets of rat and the rabbit ventricles are obtained and analysed using a novel semi-automatic image processing algorithm for segmentation of the free-running Purkinje system. Segmented geometry from the MRI datasets is used to construct a computational model of the Purkinje system, which is incorporated in to an anatomically-based ventricular geometry to simulate ventricular electrophysiological activity.

Arthroscopic excision of sternoclavicular joint.

We report an unusual case of chronic inflammatory arthropathy involving the sternoclavicular joint. Arthroscopic debridement of the sternoclavicular joint cavity was accompanied with the arthroscopic excision of the medial end of clavicle. Twelve months post-surgery the patient is asymptomatic with no signs of recurrence and a full pain free range of movement.

The added value of fibreoptic endoscopic evaluation of swallowing in tracheostomy weaning.

OBJECTIVE: To determine if fibreoptic endoscopic evaluation of swallowing adds information to the clinical assessment of swallowing in tracheostomised patients. DESIGN: A prospective, observational study. SETTING: Addenbrooke's Hospital, Cambridge, UK. PARTICIPANTS: Twenty-five consecutive, adult, tracheostomised patients were recruited over a 3-month period. They were referred to speech and language therapy for a swallowing assessment and were ready to trial cuff deflation. MAIN OUTCOME MEASURES: In current practice the clinical assessment is invariably a precursor to fibreoptic endoscopic evaluation of swallowing and a test would be considered positive when penetration or aspiration are detected. We considered the value of fibreoptic endoscopic evaluation of swallowing following both positive and negative outcomes of the clinical assessment. RESULTS: The positive predictive value of aspiration or penetration was 91% i.e. when a clinical assessment is failed, there is a very high probability the patient would also be failed on fibreoptic endoscopic evaluation of swallowing. However, the negative predictive value was only 64% i.e. over one-third of patients who pass a clinical assessment would later fail a fibreoptic endoscopic evaluation of swallowing. CONCLUSIONS: Despite a small cohort, our data suggest that the assessment of swallowing to aid weaning in tracheostomised patients is currently performed incorrectly; we estimate that over a third of all tracheostomised patients that 'pass' the clinical assessment of swallowing are, in reality, at risk from penetration, aspiration or failed decannulation. This finding supports the use of fibreoptic endoscopic evaluation of swallowing and a change in clinical practice.

Results of 1245 endoscopic carpal tunnel decompressions.

Between 1994 and 2000, the senior author performed 1245 endoscopic carpal tunnel decompressions. There were 291 bilateral cases. A telephone review was conducted of those patients who had not had an early excellent result, or conversion to an open procedure. Ninety-four per cent follow-up of patients in this group was achieved; 88% had an early excellent result with no subsequent problems. In 33 hands (3%) the carpal tunnel was opened, because of abnormal anatomy or poor view. A further 5% had a late excellent result. Seventeen hands (1%) have required subsequent open decompression, with adherence of the median nerve often found at revision surgery. Another 24 hands (2%) had a poor result. Fourteen hands (1%) had minor symptoms and 26 (2%) had another diagnosis of upper limb pathology. In contrast to other series, there was only one case of damage to an important structure - the radial digital nerve of the thumb.

Total intravenous versus inhalational anaesthesia for colonoscopy: a prospective study of clinical recovery and psychomotor function.

A randomized, prospective study was conducted on 69 patients comparing recovery after two different anaesthetic techniques for ambulatory colonoscopy. Thirty-five patients received an intravenous fentanyl (1 microg/kg), midazolam (0.05 to 0. 075 mg/kg) and propofol (10 to 20 mg boluses as required) combination. 34 patients received sevoflurane in 67% nitrous oxide. Drug administration was titrated to clinical signs. At baseline and 30, 60, 90 and 120 minutes after the procedure patient performance on a comprehensive battery of psychomotor tests was recorded. Emergence times were noted. Depth of sedation was assessed at 5 minute intervals for 30 minutes after the end of the procedure. Emergence times were faster in the fentanyl/midazolam/propofol group by 2.2 minutes. A lower sedation score was detected at 20 minutes in the sevoflurane/nitrous oxide group. Psychomotor impairment was of a greater magnitude and more prolonged by 30 to 90 minutes in the fentanyl/midazolam/propofol group. It is concluded that a sevoflurane/nitrous oxide anaesthetic has a suitable recovery profile for ambulatory colonoscopy and results in faster recovery of cognitive function compared with a fentanyl, midazolam and propofol combination.

The effects of arthroscopic acromioplasty on the acromioclavicular joint.

Thirty patients with 31 shoulders underwent clinical and radiologic evaluation 5 to 6 years after arthroscopic acromioplasty. The mean age was 51 years. The acromioclavicular (AC) joint was assessed for tenderness on palpation and pain on horizontal adduction of the shoulder. All patients underwent a radiologic examination consisting of an anteroposterior view of the AC joint and bilateral stress views. No patient had superior translation or widening of more than 1 mm of the AC joint on stress views on the unoperated side. On the operated side 12 (38%) shoulders showed signs of instability consisting of a superior translation of the clavicle of 2 to 3 mm, distraction on weight bearing view, or both. No severely osteoarthritic AC joint (grade 3 or 4) was unstable. The degree of osteoarthritis did not differ for both shoulders, suggesting that arthroscopic acromioplasty does not accelerate osteoarthritic change in the AC joint but can induce instability. Nine patients had tenderness over the AC joint and instability on stress views. They had a significantly reduced University of California Los Angeles score of 25 +/- 5 compared with the other patients (29.5 +/- 7). We conclude that preservation of the inferior capsule during arthroscopic acromioplasty is important for the integrity of the AC joint in patients without severe osteoarthritic changes.

Phosphatidate phosphohydrolases in liver, heart and adipose tissue of the JCR:LA corpulent rat and the lean genotypes: implications for glycerolipid synthesis and signal transduction.

The activities of two distinct phosphatidate phosphohydrolases (PAP) were measured in livers, hearts and adipose tissues of the JCR:LA corpulent rat which is hyperphagic, hypertriglyceridaemic and insulin resistant. The specific activity of PAP-1, which requires Mg2+, was similar in the livers of lean and corpulent female rats and in male corpulent rats, but these activities were about 1.6-fold higher than in lean males. There was a correlation between the specific activity of PAP-1 and the concentrations of hepatic and serum triacylglycerols in the males, but not in the females. Chronic treatment of the corpulent rats with ethanol did not significantly alter the hepatic activity of PAP-1, or the concentrations of hepatic or serum triacylglycerols. Specific activities of PAP-1 in the heart were higher in the lean compared to the corpulent males. There was no significant difference for the females. Specific activities of PAP-1 were over 5-fold higher in the subcutaneous adipose tissue of the corpulent males and females compared to the lean genotypes. The differences were smaller (1.6-1.9-fold) in the gonadal adipose tissue of both sexes and in the peri-renal depot for the males. PAP-1 activity in the peri-renal depots of corpulent females was 23% lower than in lean females. PAP-2 activity was insensitive to N-ethylmaleimide and did not require Mg2+ for activity. Its activity was 1.5-2.0-fold higher in the livers and hearts of the lean male and female rats than in the corpulent genotypes. Chronic treatment with ethanol increased the activity of PAP-2 in the hearts of the corpulent males, but had no effect in the corpulent females. The specific activity of PAP-2 was higher in subcutaneous, gonadal and peri-renal adipose depots in the females and in the peri-renal depot of the corpulent males compared with the lean genotypes. Lean males had higher specific activities in all three depots compared to lean females. The tissue specificity and the sex differences in the specific activities of PAP-1 and PAP-2 are discussed in terms of their proposed functions in glycerolipid biosynthesis and signal transduction. It is proposed that a decreased activity of PAP-2 could be involved in the insulin insensitivity in the corpulent rats.

Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR:LA-corpulent rats treated with D-fenfluramine.

1. The effects of D-fenfluramine were studied in the JCR:LA-corpulent rat that is grossly obese, hyperphagic, hyperlipidaemic, hyperinsulinaemic and atherosclerosis-prone. 2. Daily doses of 1, 2.5 and 5 mg kg-1 of D-fenfluramine produced sustained decreases in body weight and food intake over a period of 30 days in 6 month old female rats fed ad libitum. This was accompanied by decreases in the circulating concentrations of glucose, triacylglycerol, free cholesterol and insulin. 3. Food restriction imposed by meal feeding also decreased circulating glucose, triacylglycerols, cholesterol and insulin and diminished the effect of D-fenfluramine on these parameters in male and female rats. 4. Addition of D-fenfluramine to drinking water to give a dose of about 0.25 mg kg-1 daily produced a sustained decrease in body weight and food intake of male and female rats over a nine week period. 5. The results show that the JCR:LA-corpulent rat is very sensitive to the pharmacological effects of D-fenfluramine. These rats should provide an appropriate animal model for determining the mechanisms of action of this anti-obesity agent and whether apparently beneficial changes in metabolism translate into long-term protection against premature atherosclerosis.

Biphasic effects of glucagon and cyclic AMP on the synthesis and secretion of lipids by rat hepatocytes.

Cultured rat hepatocytes were preincubated with glucagon or a cyclic AMP analogue for up to 24 h and lipid synthesis and secretion were determined during the next 2 h. Glucagon or cyclic AMP did not change the incorporation of choline or glycerol into phosphatidylcholine, or choline into sphingomyelin, in the cells after 0-12 h of preincubation. After 12 h these incorporations were increased. Incorporations into hepatic lysophosphatidylcholine were decreased after preincubation with glucagon or cyclic AMP for 0-12 h, but by 24 h they increased. There was no change in the lysophosphatidylcholine in the medium after preincubation with glucagon or cyclic AMP for up to 6 h, but increases occurred after preincubation from 12 to 24 h. The secretion of triacylglycerol was decreased after preincubation for 0-1 h, but it returned to control values after 4 h. After preincubation for 18-24 h the incorporation of glycerol into secreted triacylglycerol was increased. The results are discussed in relation to the control of lipid metabolism in starvation and diabetes.

Decreased serum lipids, serum insulin and triacylglycerol synthesis in adipose tissue of JCR:LA-corpulent rats treated with benfluorex.

Rats of the JCR:LA-corpulent strain were treated with benfluorex daily at a dose of 25 mg/kg body weight. This strain of rat, if homozygous for the cp gene (cp/cp), is hyperphagous, obese, hypertriglyceridemic, insulin resistant and in the case of male rats, atherosclerosis prone. The benfluorex treatment produced a sharp reduction in food intake which remained suppressed despite recovery toward normal after 2 weeks of treatment. This was accompanied by sustained decreases in body weight and adipose tissue mass. The ability of adipose tissue from female rats to take up glucose and convert it to lactate, glyceride-glycerol and fatty acids was decreased. This decrease was largely due to decreased adipose tissue mass. The serum concentrations of glucose, lactate, triacylglycerol, cholesterol, phospholipids and insulin were decreased in both sexes. The treatment also improved glucose tolerance and decreased corticosterone concentrations in male rats only. While reduction of food consumption contributes to the effects seen, benfluorex clearly had significant direct metabolic effects. The effects are consistent with an improved insulin sensitivity leading to a decrease in circulating triacylglycerol. The changes produced by benfluorex are all in directions that should inhibit atherogenesis in this animal model for the human obesity/hypertriglyceridemia/insulin resistant syndrome.

Effects of the lipase inhibitors, Triton WR-1339 and tetrahydrolipstatin, on the synthesis and secretion of lipids by rat hepatocytes.

The lipase inhibitors, Triton WR-1339 and tetrahydrolipstatin, were incubated with rat hepatocytes. Triton WR-1339 increased the recovery of triacylglycerol in the hepatocytes and incubation medium by 31% and 38%, respectively. Tetrahydrolipstatin decreased the accumulation of newly synthesized, and of total triacylglycerol in the medium. This compound might be useful in determining mechanisms involved in intracellular triacylglycerol metabolism and the secretion of very low density lipoproteins.

Unsaturated fatty acids activate glycogen phosphorylase in cultured rat hepatocytes.

Oleate, linoleate, linolenate, arachidonate and eicosapentaenoate, but not myristate, palmitate and stearate, stimulated glycogen phosphorylase activity by 2-8-fold when added to cultured rat hepatocytes. Addition of BSA or Ca2- to the incubation medium decreased the stimulating effects of the unsaturated fatty acids. The combination of oleate or linolenate, with corticosterone, testosterone or estradiol produced synergistic stimulations of phosphorylase activity. The stimulation of glycogen phosphorylase activity by linolenate was inhibited by staurosporine or sphingosine. Staurosporine (80 nM) alone also decreased basal phosphorylase activities by about 60%. The results show that unsaturated fatty acids can be used as model agonists to stimulate phosphorylase activity by a mechanism that probably involves protein kinase C. On the basis of the fatty acid: BSA ratios used, this stimulation should only occur in vivo at high fatty acid concentrations when accompanied by hypoalbuminaemia.

Rapid activation of glycogen phosphorylase by steroid hormones in cultured rat hepatocytes.

Testosterone (40-300 microM), oestradiol (20-500 microM), progesterone (20-500 microM), dexamethasone (10 nM-1 microM) and corticosterone (1-10 microM) activate glycogen phosphorylase rapidly when added directly to hepatocytes. The activation of phosphorylase was concentration-dependent and occurred after 10 min for dexamethasone, 30 min for testosterone and 60 min for oestradiol and progesterone. This rapid effect does not appear to be dependent on a stimulation of protein synthesis, it is independent of an increase in cyclic AMP, and it is not diminished by the presence of ornithine decarboxylase inhibitors. The stimulation of phosphorylase activity is diminished by depleting the incubation medium of Ca2+ in the presence of 0.5 mM-EGTA, and therefore it may involve changes in the distribution of Ca2+ in the hepatocytes. These results may explain some of the pharmacological effects of sex steroids, and also might contribute to the physiological actions of glucocorticoids.

A rapid assay for measuring the activity and the Mg2+ and Ca2+ requirements of phosphatidate phosphohydrolase in cytosolic and microsomal fractions of rat liver.

1. A rapid extraction and purification scheme was designed for the recovery of [3H]diacylglycerol formed during the assay of phosphatidate phosphohydrolase. 2. The importance of removing polyvalent cations, particularly Ca2+, from the phosphatidate and other reagents used in the assay of the phosphohydrolase activity was demonstrated. This was achieved mainly by treating the phosphatidate with a chelating resin and by adding 1 mM-EGTA and 1 mM-EDTA to the assays. 3. The activity of the phosphohydrolase in dialysed samples of the soluble and microsomal fractions of rat liver was very low. 4. Addition of optimum concentrations of MgCl2 resulted in a 110-167-fold stimulation in activity. 5. CaCl2 was also able to stimulate phosphohydrolase activity, but to a much smaller extent than MgCl2. 6. Chlorpromazine, an amphiphilic cation, inhibited the reaction when it was measured in these experiments by using a mixed emulsion of phosphatidylcholine and phosphatidate at pH 7.4. 7. Microsomal fractions that were preincubated with albumin contained very low activities of the Mg2+-dependent phosphohydrolase. When these were then incubated with the soluble fraction in the presence of oleate, the soluble phosphohydrolase attached to the microsomal membranes, and it retained its high dependency on Mg2+.