Resisted Inspiration: A New Technique to Aid in the Detection of CSF-Venous Fistulas.

We describe a technique termed "resisted inspiration" that could be used during myelography to decrease superior vena cava venous pressure and increase lumbar CSF pressure, potentially aiding in the detection of CSF-venous fistulas.

Spinal Compliance Curves: Preliminary Experience with a New Tool for Evaluating Suspected CSF Venous Fistulas on CT Myelography in Patients with Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: Craniospinal space compliance reflects the distensibility of the spinal and intracranial CSF spaces as a system. Craniospinal space compliance has been studied in intracranial pathologies, but data are limited in assessing it in spinal CSF leak. This study describes a method to estimate craniospinal space compliance using saline infusion during CT myelography and explores the use of craniospinal space compliance and pressure-volume curves in patients with suspected cerebrospinal-venous fistula. MATERIALS AND METHODS: Patients with suspected cerebrospinal-venous fistula underwent dynamic CT myelography. During the procedure, 1- to 5-mL boluses of saline were infused, and incremental changes in CSF pressure were recorded. These data were used to plot craniospinal space compliance curves. We calculated 3 quantitative craniospinal space compliance parameters: overall compliance, compliance at opening pressure, and the pressure volume index. These variables were compared between patients with confirmed cerebrospinal-venous fistula and those with no confirmed source of CSF leak. RESULTS: Thirty-four CT myelograms in 22 patients were analyzed. Eight of 22 (36.4%) patients had confirmed cerebrospinal-venous fistulas. Bolus infusion was well-tolerated with no complications and transient headache in 2/34 (5.8%). Patients with confirmed cerebrospinal-venous fistulas had higher compliance at opening pressure and overall compliance (2.6 versus 1.8 mL/cm H20, P < .01). There was no difference in the pressure volume index (77.5 versus 54.3 mL, P = .13) between groups. CONCLUSIONS: A method of deriving craniospinal space compliance curves using saline intrathecal infusion is described. Preliminary analysis of craniospinal space compliance curves provides qualitative and quantitative information about pressure-volume dynamics and may serve as a diagnostic tool in patients with known or suspected cerebrospinal-venous fistulas.

Characteristics of adult- compared to childhood-onset type 1 diabetes.

AIMS: To compare diagnosis characteristics, diabetes management and comorbidities in a population diagnosed with type 1 diabetes in childhood with those in a similar population diagnosed in adulthood to identify disease differences related to the age of diabetes onset. METHODS: This analysis was performed using the T1D Exchange Clinic Registry, a cross-sectional survivor cohort. Retrospectively collected characteristics were compared across the following age-at-diagnosis groups: <10, 10-17, 18-24, 25-39 and ≥40 years. RESULTS: The entire cohort included 20 660 participants [51% female, median (interquartile range) age 18 (14-36) years, 82% non-Hispanic white]. Diabetic ketoacidosis at diagnosis was more common among those with onset in childhood. Participants diagnosed as adults were more likely to be overweight/obese at diagnosis and to have used oral agents preceding type 1 diabetes diagnosis (57%). Current insulin pump use was less frequent in participants diagnosed at older ages. Current glycaemic control, measured by HbA1c , insulin requirements and use of a continuous glucose monitor were not different by age at diagnosis. Coeliac disease was the only comorbidity that was observed to have a different frequency by age at diagnosis, being more common in the participants diagnosed at a younger age. CONCLUSIONS: These results show differences and similarities between type 1 diabetes diagnosed in childhood vs adulthood; notably, there was a tendency for there was a higher frequency of diabetic ketoacidosis at onset in children and a higher frequency of use of oral antidiabetes agents in adults. The data indicate that there is little distinction between the clinical characteristics and outcomes of type 1 diabetes diagnosed in childhood vs adulthood. Optimizing glycaemic control remains a challenge in all age groups, with lower use of insulin pumps impacting those diagnosed as adults.

Reduced Jet Velocity in Venous Flow after CSF Drainage: Assessing Hemodynamic Causes of Pulsatile Tinnitus.

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is commonly associated with transverse sinus stenosis, a venous cause of pulsatile tinnitus. In patients with idiopathic intracranial hypertension, CSF drainage via lumbar puncture decreases intracranial pressure, which relieves the stenosis, and may provide at least temporary cessation of pulsatile tinnitus. The objective of this study was to evaluate changes in venous blood flow caused by lowered intracranial pressure in patients with pulsatile tinnitus to help identify the cause of pulsatile tinnitus. MATERIALS AND METHODS: Ten patients with suspected transverse sinus stenosis as a venous etiology for pulsatile tinnitus symptoms underwent MR imaging before and after lumbar puncture in the same session. The protocol included flow assessment and rating of pulsatile tinnitus intensity before and after lumbar puncture and MR venography before lumbar puncture. Post-lumbar puncture MR venography was performed in 1 subject. RESULTS: There was a lumbar puncture-induced reduction in venous peak velocity that correlated with the opening pressure (r = -0.72, P = .019) without a concomitant reduction in flow rate. Patients with flow jets had their peak velocity reduced by 0.30 ± 0.18 m/s (P = .002), correlating with a reduction in CSF pressure (r = 0.82, P = .024) and the reduction in subjectively scored pulsatile tinnitus intensity (r = 0.78, P = .023). The post-lumbar puncture MR venography demonstrated alleviation of the stenosis. CONCLUSIONS: Our results show a lumbar puncture-induced reduction in venous peak velocity without a concomitant reduction in flow rate. We hypothesize that the reduction is caused by the expansion of the stenosis after lumbar puncture. Our results further show a correlation between the peak velocity and pulsatile tinnitus intensity, suggesting the flow jet to be instrumental in the development of sound.

Trabecular bone quality is lower in adults with type 1 diabetes and is negatively associated with insulin resistance.

We evaluated trabecular bone score (TBS) and factors affecting TBS in adults with type 1 diabetes (T1D) compared to age-, sex-, and body mass index (BMI)-matched adults without diabetes. Adults with T1D had lower TBS compared to controls. Abdominal obesity and insulin resistance are associated with lower TBS. INTRODUCTION: We evaluated TBS, a non-invasive method to evaluate trabecular bone quality at the lumbar spine, in adults with T1D compared to age-, sex-, and BMI-matched adults without diabetes. METHODS: We calculated TBS from adults with T1D (n = 47) and controls (n = 47) who had a lumbar spine dual x-ray absorptiometry (DXA) at their third visit (2006-2009) of the ongoing "Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study." The linear relationships of TBS and bone mineral density (BMD) with hemoglobin A1c, blood pressure, lipids, and insulin resistance were evaluated using Pearson's correlation coefficient. Multiple linear regression was used to test the association of TBS with sex and diabetes while adjusting for other potential confounders. RESULTS: TBS was significantly lower in adults with T1D compared to controls (1.42 ± 0.12 vs 1.44 ± 0.08, p = 0.02) after adjusting for age, sex, current smoking status, and lumbar spine BMD, despite no difference in lumbar spine BMD between the groups. Components of the metabolic syndrome, including diastolic blood pressure, BMI, triglycerides, and insulin resistance were negatively correlated with TBS among patients with T1D. CONCLUSION: Trabecular bone score, an indirect measurement of trabecular bone quality, was lower in adults with T1D compared to controls. Components of metabolic syndrome and insulin resistance were associated with lower TBS in adults with T1D.

Long-Term Effectiveness of Direct CT-Guided Aspiration and Fenestration of Symptomatic Lumbar Facet Synovial Cysts.

BACKGROUND AND PURPOSE: Lumbar facet synovial cysts are commonly seen in facet degenerative arthropathy and may be symptomatic when narrowing the spinal canal or compressing nerve roots. The purpose of this study was to analyze the safety, effectiveness, and long-term outcomes of direct CT-guided lumbar facet synovial cyst aspiration and fenestration for symptom relief and for obviating an operation. MATERIALS AND METHODS: We retrospectively reviewed the medical records and imaging studies of 64 consecutive patients between 2006 and 2016 who underwent 85 CT-guided lumbar facet synovial cyst fenestration procedures in our department. We recorded patient demographics, lumbar facet synovial cyst imaging characteristics, presenting symptoms, change in symptoms after the procedure, and whether they underwent a subsequent operation. We also assessed long-term outcomes from the medical records and via follow-up telephone surveys with patients. RESULTS: Direct CT-guided lumbar facet synovial cyst puncture was technically successful in 98% of procedures. At first postprocedural follow-up, 86% of patients had a complete or partial symptomatic response. During a mean follow-up of 49 months, 56% of patients had partial or complete long-term relief without the need for an operation; 44% of patients underwent an operation. Patients with calcified, thick-rimmed, or low T2 signal intensity cysts were less likely to respond to the procedure and more likely to need an operation. CONCLUSIONS: CT-guided direct lumbar facet synovial cyst aspiration and fenestration procedures are safe, effective, and minimally invasive for symptomatic treatment of lumbar synovial facet cysts. This procedure obviates an operation in a substantial number of patients, even at long-term follow-up, and should be considered before surgical intervention.

Bone mineral density at femoral neck and lumbar spine in adults with type 1 diabetes: a meta-analysis and review of the literature.

We performed a meta-analysis to evaluate the femoral neck and lumbar spine bone mineral density (BMD) in adults with type 1 diabetes (T1D) compared with controls. Adults with T1D have modestly lower BMD at femoral neck and lumbar spine than adults without diabetes. INTRODUCTION: Fracture risk is four to sixfold higher in adults with T1D. Since BMD is one of the major contributors for fracture risk, we performed a meta-analysis to evaluate differences in femoral neck and lumbar spine BMD between adults with T1D and controls. METHODS: MEDLINE, Ovid, and the Cochrane library and abstracts from various scientific meetings were searched. Studies reporting the femoral neck and/or lumbar spine BMD in adults (age > 20 years) with T1D in comparison with people without diabetes were selected. General linear mixed models were used to assess differences in BMD at femoral neck and lumbar spine between subjects with T1D and controls adjusting for age, sex, and dual x-ray absorptiometry (DXA) instruments. RESULTS: Sixteen studies met the inclusion criteria. The femoral neck BMD was modestly lower in adults with T1D compared to controls (-0.055 g/cm2; 95% CI: -0.065, -0.045). There were no differences in lumbar spine BMD between adults with T1D and controls (0.0062 g/cm2; 95% CI -0.04, 0.016). However, in a sensitivity analysis, lumbar spine BMD was modestly lower in adults with T1D compared to controls (-0.035 g/cm2; -0.049, -0.02). Studies using Lunar DXA instruments have reported higher lumbar spine and femoral neck BMD compared to studies using Hologic DXA instruments. CONCLUSION: Femoral neck and lumbar spine BMD were modestly lower in adults with T1D compared to controls. However, this modest reduction in femoral neck and lumbar spine BMD cannot explain much higher observed fracture risk in adults with T1D.

Type 1 diabetes and risk of fracture: meta-analysis and review of the literature.

AIMS: To conduct a systematic review and meta-analysis of observational studies in order to assess the association between Type 1 diabetes and fractures. BACKGROUND: The risk of fracture in men and women with Type 1 diabetes has not been studied in a large prospective well designed cohort. METHODS: Data were selected from Medline and Embase and abstracts from annual scientific meetings of various diabetes and bone and mineral societies. Published studies that reported the fracture risk in people with Type 1 diabetes in comparison with people without diabetes between 1990 and July 2014 and abstracts from various annual meeting (2005 onwards) were included in the present meta-analysis. Data were extracted from the text of included publications or from abstracts of conferences. RESULTS: The 14 studies that met the inclusion criteria reported 2066 fracture events among 27 300 people with Type 1 diabetes (7.6%) and 136 579 fracture events among 4 364 125 people without diabetes (3.1%). The pooled relative risk of any fracture in people with Type 1 diabetes was 3.16 (95% CI 1.51-6.63; P = 0.002). Women and men with Type 1 diabetes had a four and two times higher risk of any fractures, respectively, compared with people without diabetes. The pooled relative risks of hip fractures and spinal fractures were 3.78 (95% CI 2.05-6.98; P < 0.001) and 2.88 (95% CI 1.71-4.82; P < 0.001), respectively, among people with Type 1 diabetes. CONCLUSIONS: Our meta-analysis suggests that both men and women with Type 1 diabetes might have an increased risk of any fractures. A large prospective epidemiological study is needed to confirm our findings.

Effects of acute organophosphate poisoning on pituitary target gland hormones at admission, discharge and three months after poisoning: A hospital based pilot study.

BACKGROUND: Organophosphate compound (OPC) poisoning is common in the developing countries such as India. The acute and later effects of OPC poisoning on pituitary and target gland hormones is largely unknown. MATERIALS AND METHODS: This prospective study was conducted at Postgraduate Institute of Medical Education and Research between January 2012 and March 2013. Fourteen patients (8 males, age 18-50 years) with acute OPC poisoning were included in the study based on the history and clinical features, documented decreased in plasma cholinesterase activity or presence of the OPC in gastric lavage/blood samples. The hormonal parameters were done at baseline, at the time of discharge and at three months of follow-up. RESULTS: A total of 14 patients out of 46 with the mean age of 30.1 ± 10.3 years were finally eligible for the study. Hormonal alterations at admission were similar to sick euhormonal syndrome. Overall 7 of them had nine hormonal deficits at three months of follow up, 4 having sub normal basal cortisol level and two each had low testosterone and growth hormone and only one had thyroxine deficiency. CONCLUSION: Acute organophosphate poisoning results in endocrine dysfunction akin to sick euhormonal syndrome. However, in a small subset of patients, varying level of hormonal insufficiency may occur either at admission or later. These observations need re-validation in a larger group of patients with specific OPC.

Short-term efficacy of recombinant human GH therapy in cured acromegaly patients with GH deficiency: a single-center experience.

The effectiveness and short-term safety of recombinant human GH (r-hGH) in acromegaly patients with GH deficiency (GHD) after treatment are not well established. The study includes ten subjects with acromegaly who had GHD treated with r-hGH for 6 months. Control groups consisted of ten age-, gender-, and BMI-matched healthy subjects and ten active acromegaly patients who were treatment naïve. Body composition, quality of life (QoL), muscle strength, lipid profile, and cardiovascular risk factors were assessed in all subjects at baseline, and the same parameters were reassessed after 6 months of therapy with r-hGH in acromegaly with GHD. Repeat magnetic resonance imaging of the sella was performed in treated subjects. Optical colonoscopy was done and biopsies were taken from multiple sites for proliferation indices (Ki67). The median duration of GHD was 17.8 months and dose of r-hGH administered was 5.7±1.5 µg/kg per day. There was improvement in bone mineral content (P=0.01), bone mineral density (P=0.04), muscle strength (P<0.001), total cholesterol (P=0.003), high-density cholesterol (P<0.001), and QoL - score (P=0.005), and reduction in low-density cholesterol (P=0.003) and triglyceride (P=0.004) after treatment. There was no change in lean body mass, total body fat, hsCRP, lipoprotein (a), and fibrinogen levels. There was a modest increase in plasminogen activator inhibitor 1 (P=0.002), but it was lower compared with healthy controls and treatment naïve acromegalics (P=0.007). Six month-r-hGH therapy improves body composition, atherogenic lipid profile, QoL, and muscle strength in GHD patients who had acromegaly. Long-term prospective studies are needed to evaluate the effect of r-hGH therapy in these patients.

Congestive heart failure in acromegaly: A review of 6 cases.

BACKGROUND: Though cardiac involvement is common in acromegaly, overt congestive heart failure is uncommon. MATERIALS AND METHODS: This is retrospective analysis of hospital record between 1996 and 2007. We analyzed records of 150 consecutive patients with acromegaly. We included the patients with acromegaly those who had overt congestive heart failure either at presentation or during the course of illness for the present analysis. The diagnosis of acromegaly and congestive cardiac failure were based on standard criteria. RESULTS: Out of 150 patients with acromegaly, 6 patients had overt CHF (4.0%), of which 4 presented with the features of CHF and 2 developed during the course of illness. Three patients had hypertension and 1 had diabetes. Baseline echocardiography showed severe biventricular dysfunction and global hypokinesia in all. Angiography showed dilated hypokinetic left ventricle with normal coronaries in 3, it was confirmed at autopsy in 1. Three underwent trans-sphenoidal surgery, 1 received somatostatin analogue as primary treatment modality. Normalization of growth hormone and IGF-1 led to improvement in cardiac function in 1, 1 patient lost to follow up, and 4 died during the course of illness. In 1 patient, autopsy was performed and cardiac specimen revealed normal coronaries, concentric ventricular hypertrophy, and dilatation with myofibrolysis and interfascicular fibrosis. CONCLUSION: Prevalence of overt CHF is 4% in present series. Overt CHF carries poor prognosis and hence, this complication should be recognized at earliest, and medical management to normalized cardiac function should be given utmost priority.

Influence of age and gender on presentation of symptomatic primary hyperparathyroidism.

BACKGROUND: The geographical difference in presentation of primary hyperparathyroidism (PHPT) is known. However, there is sparse literature on the influence of age and gender on presentation of PHPT. AIM: To analyze the effect of age and gender on presentation of symptomatic primary hyperparathyroidism. SETTING AND DESIGN: This is a retrospective analysis of data from the primary hyperparathyroidism registry of a north Indian tertiary care teaching institute. MATERIALS AND METHODS: Analysis of 184 histopathologically proven PHPT patients registered between March 1990 and March 2010 from a single centre of north India. PHPT patients were divided into three different age groups i.e. children and adolescents less than 25 years, adults 25-49 years, and ≥ 50 years. Clinical presentations, biochemical parameters and parathyroid weight were compared between different age groups and gender using appropriate statistical methods. RESULTS: Mean age of patients was 38.5±13.8 years with female: male ratio of 7:3. Rickets as presenting manifestations were seen in one child and adolescent each. Prevalence of renal stones (P=0.03) and gall stones (P=0.02) was higher in the adult groups compared to the younger and older. There was no difference in bone pain (P=0.7), fracture (P=0.3), osteitis fibrosa cystica (P=0.2), fatigue (P=0.6) and other symptoms among different age groups. There was no difference in serum calcium, phosphate, parathyroid hormone (PTH) and 25 (OH) D levels among different age groups, however, as expected alkaline phosphatase was higher in adolescents compared to adults (P=0.03). Bone pain and muscle aches (P<0.001), fracture (P=0.04), osteitis fibrosa cystica (P=0.01), and gall stones (P=0.03) were more common among women while renal stones (P=0.05) and pancreatitis (P=0.02) were common in men. Serum calcium and phosphate levels were similar in either sex but parathyroid hormone (iPTH) level was higher among women (P=0.02). Parathyroid adenoma weight was higher in older compared to young but did not reach to a level of statistical significance. CONCLUSION: Age and gender have substantial influence on presentation of PHPT. Bone pain and rickets were common in children and adolescents while renal stones in adults. Women have more severe disease as musculoskeletal manifestations are common and iPTH levels are also higher compared to men.

Changes in serum leptin and adiponectin concentrations and insulin resistance after curative parathyroidectomy in moderate to severe primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is considered a state of insulin resistance. However, it is unclear whether the state of insulin resistance and adverse levels of adipocytokines are reversed in PHPT patients who have undergone curative parathyroidectomy. METHODS: Ten consecutive patients with PHPT were studied at baseline and three months after curative parathyroid surgery in this prospective interventional study. Fasting blood calcium, intact parathyroid hormone (PTH), glucose, insulin, adiponectin and leptin concentrations were measured. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA- IR) and insulin sensitivity, by the quantitative insulin sensitivity check index (QUICKI). RESULTS: Four out of the ten patients were male. The mean age of the patients was 32.40 +/- 11.42 years, and the mean body mass index was 23.70 +/- 5.19 kg/m2. The HOMA-IR value was found to be higher, while the QUICKI value was significantly lower before surgery in patients with PHPT compared to the published reference ranges. Serum leptin concentrations were higher in patients with PHPT than in normal healthy individuals; however, there was no difference in the adiponectin concentrations. There was no statistical difference in the mean values of fasting plasma glucose, plasma insulin, leptin, adiponectin, as well as the HOMA-IR and QUICKI estimates three months postoperatively, as compared to the preoperative measures. CONCLUSION: Peripheral insulin resistance/sensitivity and the concentrations of leptin and adiponectin did not change three months after curative parathyroidectomy.

Pituitary metastasis as a presenting manifestation of silent systemic malignancy: A retrospective analysis of four cases.

BACKGROUND: Pituitary metastasis as a presenting manifestation of silent systemic malignancy is rare. We describe four such cases. MATERIALS AND METHODS: Four patients (0.7%) of malignancy with pituitary metastasis out of 540 patients of sellar mass within a period of 10 years were analyzed for clinical, hormonal and radiological findings. RESULT: The age range of these patients was 39-60 years with lag time ranging from 2to 5 months. Pituitary pathology was presenting manifestation in all 4 patients including diabetes insipidus, ophthalmoplegia and variable anterior pituitary hormone deficiency. 2 patients had bronchogenic carcinoma and one each had squamous cell and adenocarcinoma with unknown primary. Diagnosis of pituitary metastasis was confirmed in three on pituitary mass histopathology and in one it was based on rapidly appearing mass in a short time. CONCLUSION: Rapidly appearing mass in the sellar region, short lag time,sudden onset of ophthalmoplegia, -symptoms and signs disproportionate to the size of mass, presence of diabetes insipidus and destroyed but normal sized sella should invoke the suspicion of pituitary metastasis.

A placebo-controlled, crossover trial of granisetron in SRI-induced sexual dysfunction.

BACKGROUND: Sexual side effects are commonly associated with serotonin reuptake inhibitor (SRI) therapy. The mechanism underlying SRI-induced sexual dysfunction has been hypothesized to be mediated by direct serotonergic effects. Evidence from open-label reports suggests that cyproheptadine, nefazodone, mirtazapine, and mianserin, which block one or more serotonin receptors, may reverse sexual side effects. The current study was a prospective, randomized, crossover trial comparing granisetron, a serotonin-3 antagonist, with placebo in outpatients who developed sexual dysfunction during SRI treatment. METHOD: Thirty-one outpatients who were currently experiencing sexual dysfunction associated with SRIs were randomly assigned to double-blind treatment with granisetron (1-1.5 mg) or placebo for use 1 to 2 hours prior to sexual activity. Patients rated sexual symptoms after each trial using the Sexual Side Effect Scale (SSES). After 4 trials of the medication, patients crossed over to the other treatment for 4 more trials. RESULTS: Twenty patients received at least 1 dose of placebo and granisetron. Analysis by repeated-measures analysis of variance showed no significant effects of granisetron relative to placebo. Significant improvement between baseline and treatment-phase SSES scores was observed for both granisetron (p = .0004) and placebo (p = .0081). The study medication was generally well tolerated. CONCLUSION: The results of this study do not support the efficacy of granisetron (1-2 mg) in the treatment of SRI-associated sexual side effects. A significant placebo response may be associated with the treatment of SRI-induced sexual dysfunction.