Normal Diagnostic Work-up Research Articles

Posterior Reversible Encephalopathy Syndrome Following Blood Transfusion: A Rare Case Report with Literature Review

Background: Posterior reversible encephalopathy syndrome (PRES) is clinicoradiological disease entity characterized by headache, seizures, altered sensorium and corticalvisual loss with characteristic MRI features of subcortical white matter hyperintensities on T2W imaging. Though hypertension is a traditional hallmark of PRES, uncommon causes without hypertension have been described. We report an unusual such case without hypertension, precipitated by red cell transfusion. Case Presentation: A 40 years female received six units of packed cell transfusion for severe anemia (Hemoglobin 3.0 Gm %) transfused over 8 hours. She was having menorrhagia and was operated on for a hysterectomy. She developed a headache on the second postoperative day for five days and no cause was revealed in spite of extensive workup, including MRI brain and CSF study. On the sixth day, she had recurrent seizures followed by altered sensorium in the absence of hypertension. Her repeat MRI brain findings were consistent with PRES. Conclusion: We reviewed 25 cases, including the present one as PRES after the blood transfusion. 24 were females, and 16 of 19 developed PRES in the course of chronic anemia lasting over 1 month. Anemia was severe in 18 of 25 cases, with haemoglobin (Hb) levels < 4.0 Gm%. In 16 of 20 cases, Hb levels increased to 5 g/dl by red cell blood transfusion until the onset of PRES. On MRI brain, 23 of 25 cases showed vasogenic edema and 3 of 25 cases showed an irreversible neurological deficit. When treating severe chronic anemia rapid correction of Hb with blood transfusion, one should consider a possibility of PRES in post-transfusion neurological symptoms in spite of normal diagnostic workup.

Increased cerebrospinal fluid chitinase 3-like 1 and neurofilament light chain in pediatric acquired demyelinating syndromes

BackgroundChitinase 3-like 1 (CHI3L1), neurofilament light chain (NFL) and oligoclonal bands (OCB) in cerebrospinal fluid are associated with central nervous system demyelination in adults. CHI3L1 and OCB are markers of central nervous system inflammation, whereas NFL is a marker of white-matter axonal injury. The aim was to examine whether CHI3L1 and NFL in cerebrospinal fluid are associated with acquired demyelinating syndromes at disease onset in a pediatric population. MethodsChildren (<18 years) referred to hospital for possible neuroinflammatory disease were retrospectively included from 2010 to 2016. Case ascertainment was by review of medical records. NFL and CHI3L1 were measured by enzyme-linked immunosorbent assays. Endpoints were differences in concentrations of cerebrospinal fluid NFL and CHI3L1. ResultsWe included 193 children who all underwent cerebrospinal fluid OCB examination as part of their diagnostic work-up and classified these children into 5 groups: acquired demyelinating syndromes (n = 33), normal diagnostic work-up (n = 36), inflammatory neurological disease (n = 50), other neurological disease (n = 55), and systemic inflammatory diseases (n = 19). NFL and CHI3L1 in cerebrospinal fluid differed significantly between the five groups (p = 0.0001). CHI3L1 was significantly higher in acquired demyelinating syndromes than in all other groups, and NFL was significantly higher in acquired demyelinating syndromes than in the other groups except systemic inflammatory disease. Children with acute disseminated encephalomyelitis had significantly higher concentrations of CHI3L1 than did children with multiple sclerosis. ConclusionWe provide class II evidence that CHI3L1 and NFL are associated with pediatric acquired demyelinating syndromes. CHI3L1 may help distinguishing between acute disseminated encephalomyelitis and multiple sclerosis, but this needs further confirmation.

Prognostic Significance of Preterm Isolated Decreased Fetal Movement

Objective: Our aim is to evaluate the prognostic significance of isolated, preterm decreased fetal movement following normal initial full diagnostic workup.Study design: A retrospective observational study was conducted at a tertiary centre. The applied protocol was approved by the Medical Research Ethics Department of the hospital where the research was conducted. Obstetrics outcomes of preterm- and term-decreased fetal movement were compared following an initial, normal diagnostic work up. Evaluated outcomes were birth weight, mode of delivery, stillbirth rate, induction of labour, development of gestational hypertension, small for gestational age and oligohydramnios, polyhydramnios during the follow up period.Result: Obstetric complications related to placental insufficiency develops more frequently for decreased fetal movement in preterm cases with respect to that of in term cases. Following the diagnosis of decreased fetal movement, pregnancy hypertension occurred in 17% of preterm decreased fetal movement cases and in 4.7% of term decreased fetal movement cases. Fetal growth restriction developed in 6.6% of preterm decreased fetal movement and in 2.3% of term decreased fetal movement. Amniotic fluid abnormalities more frequently developed in preterm decreased fetal movement.Conclusion: Following an initial normal diagnostic workup, preterm decreased fetal movement convey a higher risk for the development of pregnancy complications associated with placental insufficiency. The patient should be monitored closely and management protocols must be developed for initial normal diagnostic workups in cases of preterm decreased fetal movement.

18F-FDG-PET/CT in Multiple Myeloma: High Intense PET Positive Lesions at Diagnosis Harbor Cytogenetic Adverse Subclones

Aim:In multiple myeloma (MM), high intensity of FDG uptake in focal lesions measured as the standard uptake value (SUV) at diagnosis is associated to aggressive disease and reduced overall survival. However, the reason for high intensity FDG uptake in some focal lesions is unknown, but hypothetically such "hot" lesions could represent evolving myeloma sub-clones with particular characteristics, e.g. higher proliferative activity. We aimed to explore and characterize focal lesions with high FDG uptake and to compare the findings with random diagnostic bone marrow biopsies with lower FDG intensity or a biopsy from another lesion with lower FDG uptake. Thus, we have created a paired biopsy biobank that will be explored for molecular, biological, physiological and myeloma prognostic markers. Here we present our first data including results on morphology, immunohistochemistry, mutational, proliferative and cytogenetic status in the biopsiesMaterial and methods: CT-guided biopsies from FDG-PET positive CT-visible focal lesions in sternum, sacrum, humerus, femoral, pubic and iliac bones were taken without complications depending on accessibility and safety in 14 newly diagnosed, untreated MM patients, 2 females and 12 males, aged 53-77 years. Patients that had received steroids or bisphosphonates were excluded. Bone marrow biopsies were taken as part of the normal diagnostic work-up, but included an extra biopsy and aspirate for research. FDG uptake in the regions of interest (ROI) at focal and random bone marrow biopsy was quantified by dedicated software (ROVER, ABX, Radeberg, Germany) to obtain the following variables: Lesion volumes, SUVmax, SUVpeak, cSUVmean (SUVmean corrected for partial volume effect). The paired biopsies were analyzed for: Myeloma plasma cells percentage (PC%), myeloma cell proliferation (Ki67 positive fraction of CD138 positive cells (Ki67/CD138%), myeloma cell MYC protein expression (MYC/CD138%), FISH aberrations in % of myeloma cells (del17p, del13q, del1p, amp1q, t(11;14), t(4;14), BRAF mutation and specific p16, p27, and p53 protein expressions by IHC in % of MM cells.Results: 13 patients were evaluable for analysis with paired datasets. One patient was excluded due to a normal bone marrow examination (multifocal myeloma). ROI SUVmax values ranged from 2.6 to 22.16 and differences in SUVmax between paired biopsies ranged from 0.4 to 17.1. First of all, we found myeloma malignancy in all PET-positive CT-guided biopsies. Comparing the findings in "hot" versus "random" biopsy groups we found significantly higher PC%s in the "hot" biopsy group (p=0.01) but this was not a consistent finding in all patients. PC proliferation rate (Ki67/CD138) was higher in some of the "hot" biopsies but this was neither a uniform observation. No difference in "primary event" chromosome 14q translocations was observed, whereas we identified subclones with typical cytogenetic secondary or late events in several "hot" biopsies that were not present in the random bone marrow biopsy: amp1q in 3 patients, del1p in 1 patient, del13q and del17p in 1 patient. MYC protein expression was higher in "hot" biopsies in 4 patients, and downregulation of p27 was evident in 2 patients. We found no unbalanced expression of p53 or p16, and in only one patient we identified a BRAF mutated subclone that was equally present in the "hot" and "random" biopsy (20% vs 30%). Few patients presented more adverse findings in the "hot" biopsies. Overall, MM adverse findings were present unbalancedly in 8 of 13 patients.Conclusion: We did not identify a mutual factor that explained the more intense FDG uptake in CT guided biopsies than in random bone marrow, e.g. a higher PC Ki67 expression. However, in 8 of 13 patients we identified 1 or more prognostic adverse, unbalanced findings in the PET positive focal lesions indicating presence of more aggressive subclones. These findings are concordant with the adverse prognostic importance of finding high-intense PET-positive focal lesions on FDG-PET/CT in newly diagnosed MM patients. DisclosuresNo relevant conflicts of interest to declare.

Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability,d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis

Background: Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). Objective: To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. Design: Diagnostic management study. (ClinicalTrials.gov: NCT01324037) Setting: 16 hospitals in Europe and the United States. Patients: 406 inpatients and outpatients with suspected UEDVT. Measurements: The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. Results: The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). Limitations: This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. Conclusion: The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. Primary Funding Source: None.

Unusual presentation for a patent ductus arteriosus

A 63-yr-old black female, with a 1-yr history of hepatitis C and ascites was referred to an expert centre with suspicion of portopulmonary hypertension (PPHTN). Her poor condition made a rapid diagnosis imperative and precluded a normal diagnostic work-up. Echocardiography confirmed severe pulmonary hypertension (PH). A hepatic scintigraphy and an abdominal echo-Doppler study excluded liver cirrhosis and portal hypertension. Cardiac magnetic resonance imaging showed marked dilation of the right ventricle with significant hypertrophy of the free wall, a finding that is uncommon in idiopathic pulmonary arterial hypertension or PPHTN. Right heart catheterisation demonstrated severe pre-capillary PH without response to acute vasodilator testing. Finally the patient underwent computed tomography angiography, which showed marked dilation of the pulmonary artery without thromboembolic disease and, unexpectedly, a partially calcified large patent ductus arteriosus. The correct diagnosis of the underlying cause of pulmonary arterial hypertension is essential. Patients with underlying heart defects may have an atypical presentation and be referred to expert centres with an incorrect diagnosis. A full investigation is necessary; careful examination of right ventricular anatomy can provide clues about the aetiology of PH, and it is important to exclude intra- and extracardiac shunts during haemodynamic studies.