Prediction of dementia using diffusion tensor MRI measures: the OPTIMAL collaboration.

OBJECTIVES: It has been suggested that diffusion tensor imaging (DTI) measures sensitive to white matter (WM) damage may predict future dementia risk not only in cerebral small vessel disease (SVD), but also in mild cognitive impairment. To determine whether DTI measures were associated with cognition cross-sectionally and predicted future dementia risk across the full range of SVD severity, we established the International OPtimising mulTImodal MRI markers for use as surrogate markers in trials of Vascular Cognitive Impairment due to cerebrAl small vesseL disease collaboration which included six cohorts. METHODS: Among the six cohorts, prospective data with dementia incidences were available for three cohorts. The associations between six different DTI measures and cognition or dementia conversion were tested. The additional contribution to prediction of other MRI markers of SVD was also determined. RESULTS: The DTI measure mean diffusivity (MD) median correlated with cognition in all cohorts, demonstrating the contribution of WM damage to cognition. Adding MD median significantly improved the model fit compared to the clinical risk model alone and further increased in all single-centre SVD cohorts when adding conventional MRI measures. Baseline MD median predicted dementia conversion. In a study with severe SVD (SCANS) change in MD median also predicted dementia conversion. The area under the curve was best when employing a multimodal MRI model using both DTI measures and other MRI measures. CONCLUSIONS: Our results support a central role for WM alterations in dementia pathogenesis in all cohorts. DTI measures such as MD median may be a useful clinical risk predictor. The contribution of other MRI markers varied according to disease severity.

Adrenal Ganglioneuroma.

Adrenal ganglioneuromas are rare sympathetic differentiated tumors which originate from neural crest cells. These lesions are usually discovered incidentally on imaging and tend to be hormonally silent. Preoperative diagnosis of adrenal ganglioneuroma remains extremely challenging and the gold standard treatment is adrenalectomy. There is good prognosis after surgery without recurrence. We herein report a case of adrenal ganglioneuroma in a 15 year old female who presented with complaint of abdominal discomfort. Contrast Enhanced Computed Tomography abdomen showed a large septated hypodense right suprarenal mass which was echogenic on Ultrasonography. It showed T1 hypointense and T2 hyperintense signal on Magnetic Resonance Imaging of abdomen and pelvis. Excisional biopsy and histological examination of the mass was suggestive of adrenal ganglioneuroma. This report presents the clinical and radiological data for the rare tumor which would share some experience to facililate the diagnosis of adrenal ganglioneuroma.

White matter changes and gait decline in cerebral small vessel disease.

The relation between progression of cerebral small vessel disease (SVD) and gait decline is uncertain, and diffusion tensor imaging (DTI) studies on gait decline are lacking. We therefore investigated the longitudinal associations between (micro) structural brain changes and gait decline in SVD using DTI. 275 participants were included from the Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort (RUN DMC), a prospective cohort of participants with cerebral small vessel disease aged 50-85 years. Gait (using GAITRite) and magnetic resonance imaging measures were assessed during baseline (2006-2007) and follow-up (2011 - 2012). Linear regression analysis was used to investigate the association between changes in conventional magnetic resonance and diffusion tensor imaging measures and gait decline. Tract-based spatial statistics analysis was used to investigate region-specific associations between changes in white matter integrity and gait decline. 56.2% were male, mean age was 62.9 years (SD8.2), mean follow-up duration was 5.4 years (SD0.2) and mean gait speed decline was 0.2 m/s (SD0.2). Stride length decline was associated with white matter atrophy (ß = 0.16, p = 0.007), and increase in mean white matter radial diffusivity and mean diffusivity, and decrease in mean fractional anisotropy (respectively, ß = - 0.14, p = 0.009; ß = - 0.12, p = 0.018; ß = 0.10, p = 0.049), independent of age, sex, height, follow-up duration and baseline stride length. Tract-based spatial statistics analysis showed significant associations between stride length decline and fractional anisotropy decrease and mean diffusivity increase (primarily explained by radial diffusivity increase) in multiple white matter tracts, with the strongest associations found in the corpus callosum and corona radiata, independent of traditional small vessel disease markers. White matter atrophy and loss of white matter integrity are associated with gait decline in older adults with small vessel disease after 5 years of follow-up. These findings suggest that progression of SVD might play an important role in gait decline.

Diffusion tensor imaging of the hippocampus predicts the risk of dementia; the RUN DMC study.

INTRODUCTION: Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume. METHODS: The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level. RESULTS: 43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia. CONCLUSION: This is the first prospective study showing a relation between a higher baseline hippocampal mean diffusivity and the risk of incident dementia in elderly with small vessel disease at 5-year follow-up, independent of hippocampal volume and white matter volume.

Normal fetal nasal bone length at 14 to 28 weeks of gestation.

The fetal nasal bone length (FNBL) is a recent sonographic marker included in second trimester genetic sonography which varies with race and ethnicity. The importance of measuring FNBL is in the prenatal diagnosis of Down's syndrome (DS), the most common chromosomal abnormality. Nasal bone hypoplasia or absence is one of the frequent features of DS. Different studies conducted in different parts of the world have established FNBL in different races. But, reference values for normal fetal nasal bone length are yet to be established for Nepalese population. So, the aim of this study was to determine normal FNBL in second trimester. Objective was to create normal reference values for fetal nasal bone in Nepalese population. A cross sectional study was carried out on 150 second trimester pregnancy cases referred for antenatal ultrasound to Department of Radiology at Nepal Medical College and Teaching Hospital between May 2014 and July 2014. Cases included all the clinically normal second trimester pregnancy in which fetal nasal bone could be visualized in midsagittal plane. Table demonstrating normal FNBL corresponding to weeks of gestation was generated using IBM SPSS Statistics Version 20. There was linear increase in mean FNBL with gestational age. Minimum mean FNBL was 2.93 mm at 14 weeks and maximum was 7.89 mm at 27 weeks. Age of patients ranged from 17 to 35 years. Normal FNBL values in Nepalese population corroborates with those published in Western literature but with variation. Hence, reference values for local population become more relevant for antenatal ultrasound practices in Nepal.

USG assisted and USG guided percutaneous renal biopsy at Nepal Medical College Teaching Hospital: a three and half years study.

A prospective study was carried out from 2009 to 2013 in the Department of Radiology and Imaging of Nepal Medical College and Teaching Hospital, Attarkhel, Jorpati, Kathmandu, Nepal, in which a total of 75 patients underwent percutaneous renal biopsy with a 16 or 18 gauge needles. This was done blindly by marking a site on the skin, or, whenever there was difficulty with the blind procedure, by direct real time USG guidance. In all cases, the marking in the skin was done by the radiologist and the biopsy was performed by the Nephrologist, with the aid of the radiologist in cases of real-time USG guided renal biopsy. This study was carried out to assess the safety and efficacy of the USG aided, and USG guided renal biopsy, to see for the types and severity of complications arising from renal biopsies to determine the optimal period of observation required after the procedure. All renal biopsies were performed after the patients were admitted to the hospital at least 1 day prior to the procedure. Coagulation profile was done in all patients prior to the procedure. All patients were kept under strict complete bed rest for 24 hours post procedure. The ages of the patients ranged between 14 years to 71 years, with 42 female and 33 male patients. A mean of 21.8 glomeruli was obtained in each specimen, with absent glomerular yield seen in only 3 patients. Minimal change disease was seen in 19 patients, being the most common histopathological diagnosis followed by a spectrum of others. The overall complication rate was 4% and all of these were self-limiting needing no other intervention, or management except for observation and bed rest. Late complications were not seen. Percutaneous renal biopsy with the help of USG is a safe and efficacious procedure with less chance of minor complications.

Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease: the RUN DMC study.

BACKGROUND: Cerebral small vessel disease (SVD) is related to verbal memory failures. It is suggested that early white matter damage, is located, among others, in the (posterior) cingulum at an early stage in neurodegeneration. Changes in the microstructural integrity of the cingulum assessed with diffusion tensor imaging (DTI), beyond detection with conventional MRI, may precede macrostructural changes and be related to verbal memory failures. OBJECTIVE: To investigate the relation between cingular microstructural integrity and verbal memory performance in 503 non-demented elderly with cerebral SVD. METHODS: The RUN DMC study is a prospective cohort study in elderly (50-85 years) with cerebral SVD. All participants underwent T1 MPRAGE, FLAIR and DTI scanning and the Rey Auditory Verbal Learning Test. Mean diffusivity (MD) and fractional anisotropy (FA) were assessed in six different cingular regions of interests (ROIs). Linear regression analysis was used to assess the relation between verbal memory performance and cingular DTI parameters, with appropriate adjustments. Furthermore a TBSS analysis of the whole brain was performed to investigate the specificity of our findings. RESULTS: Both our ROI-based and TBSS analysis showed that FA was positively related to immediate memory, delayed recall, delayed recognition and overall verbal memory performance of the cingulum, independent of confounders. A similar distribution was seen for the inverse association with MD and verbal memory performance with TBSS analysis. No significant relations were found with psychomotor speed, visuospatial memory and MMSE. When stratified on hippocampal integrity, the MD and FA values of the cingular ROIs differed significantly between participants with a good and poor hippocampal integrity. CONCLUSION: Microstructural integrity of the cingulum, assessed by DTI, is specifically related to verbal memory performance, in elderly with SVD. Furthermore we found that when the integrity of the hippocampus is disrupted, the cingulum integrity is impaired as well.

HLA antigen distribution in renal transplant recipients and donors.

BACKGROUND: HLA typing analysis is important in renal transplant patient. This study is the first report from Nepal to find out distribution of HLA A, B, DR antigen in live related renal transplant recipients and donors from Nepal. The aim of this study was to investigate the distribution of HLA in the live related renal transplant recipients and donors of Nepal. METHODS: In a retrospective study, HLA patterns were defined in 100 live related renal transplant recipients and donors. One year study is done from June 2011 to May 2012. The study was done by using sequence specific oligonucleotides primers and polymerase chain reaction and assay. Allele frequencies were obtained by direct counting. RESULTS: A total of 12 HLA-A, 15 HLA-B and 13 HLA-DRB1 alleles were identified at the four-digit level in the live related renal transplant recipients and donors of Nepal. High frequency alleles were HLA-A*11 (34.5%), A*24 (17%), A*33 (13%); HLA-B*15(27%), B*35(19%), B*40 (10%); HLA-DRB1*15 (33.5%), DRB1*12 (21.4%) and DRB1*04 (7.32%). CONCLUSIONS: These results showed considerable heterogeneity in both HLA class I and class II antigens. To reduce the risk of allograft rejection, transplantation from HLA matched donors is recommended.

Advanced maternal age and obstetric outcome.

Advanced maternal age defined as age 35 years or more at estimated date of delivery is considered to have higher incidence of obstetric complications and adverse pregnancy outcome than younger women. The objective of this study was to compare the obstetric and perinatal outcome of pregnancies in women with advanced maternal age > or = 35 years with that of younger women < 35 years. A prospective comparative study was carried out in department of obstetrics and gynecology at Nepal Medical College and Teaching Hospital over the period of one year from October 2012 to September 2013. The obstetric and perinatal outcome of 90 women with advanced maternal age (study group) were compared with those of 90 younger women aged 20-34 years (control group). Among antenatal complications, women of advanced maternal age had increased incidence of hypertensive disorder of pregnancy (26.6% vs 4.4%; p = 0.00009) and breech presentation (8.8% vs 1.1%; p = 0.04). There were no significant difference between two groups in incidence of antepartum hemorrhage, gestational diabetes mellitus, prelabor rupture of membrane and preterm delivery. The rate of caesarean delivery was significantly higher in advanced maternal age (28.8% vs 17.7%; p = 0.05). In perinatal outcome, older women had significantly higher incidence of perinatal death (7.7% vs 0%; p = 0.01). There were no significant differences in low birth weight rate and apgar score less than 7 at five minutes of life in two groups. Thus from this study, it can be concluded that advanced age women had higher incidence of hypertensive disorder of pregnancies and malpresentation, were more likely to deliver by caesarean section and had increased incidence of perinatal death.

Carotid Doppler and lipid profile findings in ischemic stroke patients--a hospital based study.

A prospective study was carried out during 2010 - 2011 in the Department of Radiology & Imaging of Nepal Medical College and Teaching Hospital, Jorpati, Kathmandu and Om Hospital and Research Centre, Chabahil, Kathmandu in which a total of 45 patients with clinically and CT scan diagnosed ischaemic cerebrovascular accident (CVA) underwent carotid Doppler study. During the hospital stay these patients also underwent lipid profile estimation to see for presence or absence of hyperlipidemia. Of these 45 patients, CT scan showed left middle cerebral artery (MCA) infarctions in 12, right MCA infarction in 12, lacunar infarctions in 10, watershed territory infarction in 4, posterior circulation infarction in 1 and venous infarction in 1 patient. Carotid Doppler study showed more than 50% stenosis in 31 patients. Among these 31 patients, 28 had hyperlipidemia where as blood cholesterol and triglyceride values in 3 patients were normal. The present study like several other studies done in the past showed association between carotid stenosis and hyperlipidemia, leading to CVA.

Role of USG guided FNAC in diagnosis of abdominal and thoracic lesions.

A prospective study was carried out during 2010 - 2012 in which a total of 194 patients underwent USG guided FNAC from lesions in deep seated thoracic and abdominal organs. These included liver, lungs, intra-abdominal lymphnodes, gall bladder, ovary and adnexa, pancreas, stomach, omentum, other mass of unknown origin in peritoneal cavity, mediastinum, kidney, colon, small intestine, pleura, appendix and adrenal gland. Of these, FNAC was diagnostic in 168 (86.7%) cases, in 15 (7.7%) cases it was not conclusive. In next 6 (3.1%) it was suspicious of malignancy and the smears were acellular and /or contained blood only in 5 (2.6%) cases. Of all diagnosed cases, 153 (78.9%) cases were malignant, 28 (14.4%) were non-noplastic which included inflammatory, infective and granulomatous lesions and 13 (6.7 %) were benign neoplastic lesions. In liver, metastatic adenocarcinoma was the most common FNAC diagnosis, in lungs non-small cell carcinoma. The aim of this study was to evaluate the overall role of USG guided FNAC in diagnosis of abdominal and thoracic lesions.

Sonographic assessment of placental migration in second trimester low lying placenta.

To assess the migration of low lying placenta diagnosed in the second trimester ultrasonogram (USG). All the women attending antenatal OPD clinic had undergone routine obstetric USG in the second trimester (14 weeks onwards). Those cases who had low lying placenta lower edge of placenta within 3.0 cms from the cervical internal os were included in the study. These cases were subjected to be followed up at 4 weekly interval to repeated serial ultrasonogram by Transabdominal and/or Transvaginal USG well through 3rd trimester of pregnancy or delivery which ever was earlier. Of the total 1229 second trimester USG, 312 (25.3%) women had low lying placenta in the second trimester. Follow up of this 312 cases indicated that in 288 (92.4%) cases it had migrated to upper segment by 3rd trimester. The migration of placenta was 92.4% and 68.0 % where the distance between the leading edge of placenta and cervical internal os was more than 2.0 cm or less than 2 cm respectively. Migration was not observed in women where the distance was less than 1.5 cm. Placental migration was 94.5% in anteriorly situated placenta and 90.2% in posteriorly situated placenta. The rate of placental migration was 95.1%, 77.7%, 55.5% in women who had previous normal delivery, previous caesarean delivery and prior history of dilatation and curettage (D & C) or manual removal of placenta (MRP), respectively. The prevalence of low lying placenta in 2nd trimester is 25.3%, which reduces to 7.3% at term. The rate of placental migration was over 90.0%. Factor like initial distance between the lower edge of the placental and cervical internal os. placental position and previous birth by caesarean section influence the placental migration.

Prospective study of medical abortion in Nepal Medical College Teaching Hospital (NMCTH). A one year experience.

A combination of antiprogesterone mifepristone and prostaglandin analogue misoprostol provides an effective non surgical method for termination of pregnancy up to gestational age of 63 days. The objective of this study was to assess the efficacy of this medical regimen for termination of pregnancy up to 63 days of pregnancy. A hospital based prospective study was carried out in department of obstetrics and gynecology at Nepal Medical College Teaching Hospital (NMCTH) for a period of one year where 100 women requesting for medical abortion were enrolled. The medical regimen used was mifepristone 200 mg orally followed 24 hours later by misoprostol 800 micrograms administered buccally. Most of the women were in age group 20-29 years (50%), were nulliparous (81%) and were within 42 days of pregnancy (47%). The overall success rate of this regimen was 93.6%. Where success was defined as achieving complete abortion without needing surgical evacuation. Surgical evacuation was needed in 6 (6.4%) patients i.e. 5 for incomplete abortion and one for continued viable pregnancy. The combination of oral mifepristone 200mg followed 24 hours later by buccal misoprostol 800mcg is effective method of medical termination of pregnancy.

Deep-seated thoracic and abdominal lesions: usefulness of ultrasound guided fine needle aspiration cytology, a 3 year experience.

Three hundred twenty patients were subjected to ultrasound guided fine needle aspiration cytology (FNAC) over a 3 year period (April 2006 - March 2009). These included liver (125 cases), lung (81 cases), abdominal and mediastinal lymph nodes (29 cases), ovary (14 cases), omentum (12 cases), pancreas (10 cases), kidney (10 cases), mediastinum (8 cases), gall bladder (8 cases) etc. The aim of this study was to evaluate the overall utility of ultrasonographic guided FNAC in the diagnosis of abdominal and thoracic lesions. In 264 cases (82.5%), FNAC was diagnostic with commonest diagnosis being malignant neoplasm (70.0%). 14 cases (4.4%) were suspicious of malignancy and remaining 42 (13.1%) cases either didn't reveal diagnostic material or they were inconclusive. In liver, Metastatic adenocarcinoma is the commonest tumor, while in lung; the commonest lesion is non-small cell carcinoma. Benign neoplasm (3.1%) and non neoplastic lesion (9.4%) were also diagnosed by FNAC. Rare sites like oesophagus and duodenum were also aspirated. Complication rate was too low (0.9%) in this study. USG guided FNAC, in conjunction with clinico-radiological parameters are accurate and safe in diagnosing deep-seated mass lesions in the thorax and abdomen.

Role of ultrasound in early pregnancy in differentiating normal and abnormal pregnancies.

A prospective study was carried out from November 2006 - December 2008 in which a total of 304 patients with early pregnancy were examined by ultrasound (US). Of these, 203 (66.8%) cases were normal pregnancies (including 8 cases of twin pregnancy), 32 (10.5%) missed abortions, 19 (6.3%) incomplete abortions, 14 (4.6%) complete abortions, 12 (4.0%) blighted ovums, 11 (3.6%) without sonographic evidence of pregnancy, 7 (2.3%) ectopic pregnancies and 6 (1.9%) molar pregnancies. US in early pregnancy gave a reliable and accurate differentiation between a viable normal pregnancy and an abnormal/pathological pregnancy.

Detection of tubal abnormalities by HSG in Nepalese subfertile women.

Fallopian tube defects are responsible for subfertility in 12.0-33.0% of subfertile couple. Hysterosalpingography (HSG) is a safe and less invasive method of detecting both the tubal and uterine defects. The objective of this study was to find out the incidence of tubal blockage including its site and side diagnosed by HSG in subfertile Nepalese women and to find out the incidence of uterine and other abnormalities detected by this test. This was a prospective study of 1000 cases of subfertility, conducted in Om Hospital, Kathmandu. A short history and HSG report of these cases were obtained from the Radiology department of the hospital. Size and shape of the uterine cavity, evidence of cervical incompetence, tubal visualization, spillage of dye, tubal block with its side and site, evidence of peritoneal adhesion and intravasation of dye in vessels were noted. Quick spillage of the dye in the peritoneal cavity or spillage only after pushing the dye with pressure was also noted. Results were entered in simple tabulations and analyzed. Among 1000 cases, 65.8% had primary and 34.2% had secondary subfertility. 29.0% of the total 1000 cases had abnormal HSG findings. 19.0% of total 1000 cases had tubal blockage. Incidence of tubal blockage in both primary (19.1%) and secondary subfertilty (18.7%) was almost same, in contrary to previous belief. Mullerian defect was present in 3.2% of primary subfertility and 2.0% of secondary subfertility cases. Cervical incompetence was not detected in any case. Evidence of uterine infection was present in 0.7% of primary subfertility and 0.2% of secondary subfertility cases. Abnormal size of uterine cavity was present in 1.2% of primary subfertility and 0.5% of secondary subfertility. Features of phimosis of fimbrial opening, localized spill and intravasation of dye were present respectively in 5.6%, 1.5%, 1.2% in primary subfertility and 4.9%, 1.7% and 1.7% in secondary subfertility.In conclusion; the incidence of tubal blockage detectable by HSG in this study was 19.0%.