Lumbar disc extrusions reduce faster than bulging discs due to an active role of macrophages in sciatica.

OBJECTIVE: This retrospective observational histological study aims to associate the size and type of disc herniation with the degree of macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica. METHODS: Disc tissue of 119 sciatica patients was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0-10/cm2), moderate (10-100/cm2), and considerable (> 100/cm2) macrophage infiltration. All 119 patients received an MRI at baseline, and 108 received a follow-up MRI at 1-year. MRIs were reviewed for the size and type of the disc herniations, and for Modic changes in the vertebral endplates. RESULTS: Baseline characteristics and duration of symptoms before surgery were comparable in all macrophage infiltration groups. The degree of macrophage infiltration was not associated with herniation size at baseline, but significantly associated with reduction of size of the herniated disc at 1-year post surgery. Moreover, the degree of macrophage infiltration was higher in extrusion in comparison with bulging (protrusion) of the disc. Results were comparable in patients with and without Modic changes. CONCLUSION: Macrophage infiltration was positively associated with an extruded type of disc herniation as well as the extent of reduction of the herniated disc during 1-year follow-up in patients with sciatica. This is an indication that the macrophages play an active role in reducing herniated discs. An extruded disc herniation has a larger surface for the macrophages to adhere to, which leads to more size reduction.

Interobserver variability in the radiological assessment of magnetic resonance imaging (MRI) including perfusion MRI in glioblastoma multiforme.

BACKGROUND AND PURPOSE: Conventional magnetic resonance imaging (MRI) has limited value for differentiation of true tumor progression and pseudoprogression in treated glioblastoma multiforme (GBM). Perfusion weighted imaging (PWI) may be helpful in the differentiation of these two phenomena. Here interobserver variability in routine radiological evaluation of GBM patients is assessed using MRI, including PWI. METHODS: Three experienced neuroradiologists evaluated MR scans of 28 GBM patients during temozolomide chemoradiotherapy at three time points: preoperative (MR1) and postoperative (MR2) MR scan and the follow-up MR scan after three cycles of adjuvant temozolomide (MR3). Tumor size was measured both on T1 post-contrast and T2 weighted images according to the Response Assessment in Neuro-Oncology criteria. PW images of MR3 were evaluated by visual inspection of relative cerebral blood volume (rCBV) color maps and by quantitative rCBV measurements of enhancing areas with highest rCBV. Image interpretability of PW images was also scored. Finally, the neuroradiologists gave a conclusion on tumor status, based on the interpretation of both T1 and T2 weighted images (MR1, MR2 and MR3) in combination with PWI (MR3). RESULTS: Interobserver agreement on visual interpretation of rCBV maps was good (κ = 0.63) but poor on quantitative rCBV measurements and on interpretability of perfusion images (intraclass correlation coefficient 0.37 and κ = 0.23, respectively). Interobserver agreement on the overall conclusion of tumor status was moderate (κ = 0.48). CONCLUSIONS: Interobserver agreement on the visual interpretation of PWI color maps was good. However, overall interpretation of MR scans (using both conventional and PW images) showed considerable interobserver variability. Therefore, caution should be applied when interpreting MRI results during chemoradiation therapy.

Vaccination against H1N1 influenza with Pandemrix(®) during pregnancy and delivery outcome: a Swedish register study.

OBJECTIVE: To describe a large study on pregnancy outcome after vaccination against H1N1 during the 2009/10 pandemic. DESIGN: A cohort study of women vaccinated with Pandemrix(®) during pregnancy. SETTING: The Swedish Medical Birth Register was used for the analysis. Information on vaccination and pregnancy week when vaccination was made was obtained from antenatal care documents. POPULATION: All women who gave birth during 2009 and 2010 in Sweden. METHODS: Characteristics of the vaccinated women and their delivery outcome were compared with two groups of women: women without a known vaccination who gave birth in 2009/10 after 1 October 2009, and women who gave birth during 2009 before 1 October. Adjustment was made for year of delivery, maternal age, parity, smoking habits and body mass index. OUTCOME MEASURES: Stillbirth, congenital malformations, preterm birth, low birthweight, small for gestational age. RESULTS: A total of 18 612 vaccinated women having 18 844 infants were studied. The risk for stillbirth, preterm birth and low birthweight was lower than in the comparison groups whereas the risk for small for gestational age and a congenital malformation (after vaccination during the first trimester) did not differ from the comparison groups. No clear-cut explanation to the 'protective' effect of vaccination was found. CONCLUSIONS: Vaccination during pregnancy with Pandemrix(®) appeared to have no ill effects on the pregnancy. On the contrary, the rate of preterm birth and low birthweight was lower than expected, which agrees with some previous results.

Malignancies among women who gave birth after in vitro fertilization.

BACKGROUND: Relatively few studies published to date have investigated IVF and cancer risk. In this study we compared the occurrence of cancer in women who gave birth after IVF with all other women who gave birth in the study period. METHODS: All women who were treated with IVF and gave birth during the years 1982-2006 in Sweden were identified from all IVF clinics, and the occurrence of cancer in these women was identified by linkage with the nationwide Swedish cancer register. Comparison was made with Mantel-Haenszel odds ratios (ORs), adjusting for year of delivery and maternal age, parity and smoking. Cancer before IVF was only studied in first parity women. Specific cancer forms were also studied. RESULTS: Among 24058 women who had been treated with IVF, 1279 appeared in the cancer register. The total number of women studied in the population was 1 394 061, and 95 775 of these were registered in the cancer register. The risk for cancer before IVF was increased [OR 1.37, 95% confidence interval (CI) 1.27-1.48] and was especially high for ovarian cancer (3.93). The risk for cancer after IVF was significantly lower (OR 0.74, 95% CI 0.67-0.82), mainly due to a lower than expected risk for breast and cervical cancer. The risk for ovarian cancer was increased but lower than the risk before IVF (2.13). CONCLUSIONS: Cancer or cancer treatment may increase the risk for infertility leading to IVF. After IVF, in most cases with treatment with fertility hormones, a significantly low cancer risk was found. Ovarian cancer showed an increased risk, although lower than before IVF. One possible reason is ovarian pathology causing both infertility and an increased cancer risk.

Interobserver agreement on MRI evaluation of patients with cervical radiculopathy.

AIM: To evaluate the interobserver agreement on magnetic resonance imaging (MRI) evaluation of herniated discs, spondylotic neuroforaminal stenosis, and root compression in patients with recent onset cervical radiculopathy and in addition, to assess the added value of disclosure of clinical information to interobserver agreement. MATERIALS AND METHODS: The MRI images of 82 patients with less than 1 month of symptoms and signs of cervical radiculopathy were evaluated independently by two neuroradiologists who were unaware of clinical findings. MRI analysis was repeated after disclosure of clinical information. Interobserver agreement was calculated using kappa statistics. RESULTS: The kappa score for evaluation of herniated discs and of spondylotic foramen stenosis was 0.59 and 0.63, respectively. A kappa score of 0.67 was found for the presence of root compression. After disclosure of clinical information kappa scores increased slightly: from 0.59 to 0.62 for the detection of herniated discs, from 0.63 to 0.66 for spondylotic foramen stenosis, and from 0.67 to 0.76 for root compression. CONCLUSION: Interobserver reliability of MRI evaluation in patients with cervical radiculopathy was substantial for root compression, with or without clinical information. Agreement on the cause of the compression, i.e., herniated disc or spondylotic foraminal stenosis, was lower.

Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years.

BACKGROUND: Marked changes have occurred in in vitro fertilization (IVF) methodology during the past 25 years but also in characteristics of couples undergoing treatment. METHODS: This study was based on 27 386 women undergoing IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of deliveries were studied using Swedish health registers. Comparisons were made with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were calculated when important changes in background rates had occurred. RESULTS: There was a substantial increase in the use of intracytoplasmatic sperm injection (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the proportion using epididymal or testicular sperm varied between 5 and 10%. Maternal characteristics changed during the observation period but the median age remained relatively constant in spite of the increasing maternal age in the population. There was a decline in the rate of some maternal pregnancy diagnoses (notably pre-eclampsia, premature rupture of membranes) and some neonatal diagnoses (notably preterm births, low birthweight, cerebral hemorrhage, respiratory diagnoses, use of continuous positive airway pressure and mechanical ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% towards the end of the period whereas higher order multiples nearly disappeared. The total rate of infants with congenital malformations changed only little. CONCLUSIONS: The decrease in unwanted outcomes can, to a large extent, be explained by the reduced rate of multiple births but was seen also among singletons. Other explanations can be sought in changes in the characteristics of patients undergoing IVF.

Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data.

BACKGROUND: Concerns have been expressed about possible adverse effects of the use of antidepressant medication during pregnancy, including risk for neonatal pathology and the presence of congenital malformations. METHOD: Data from the Swedish Medical Birth Register (MBR) from 1 July 1995 up to 2007 were used to identify women who reported the use of antidepressants in early pregnancy or were prescribed antidepressants during pregnancy by antenatal care: a total of 14 821 women with 15 017 infants. Maternal characteristics, maternal delivery diagnoses, infant neonatal diagnoses and the presence of congenital malformations were compared with all other women who gave birth, using the Mantel-Haenszel technique and with adjustments for certain characteristics. RESULTS: There was an association between antidepressant treatment and pre-existing diabetes and chronic hypertension but also with many pregnancy complications. Rates of induced delivery and caesarean section were increased. The preterm birth rate was increased but not that of intrauterine growth retardation. Neonatal complications were common, notably after tricyclic antidepressant (TCA) use. An increased risk of persistent pulmonary hypertension of the newborn (PPHN) was verified. The congenital malformation rate was increased after TCAs. An association between use of paroxetine and congenital heart defects was verified and a similar effect on hypospadias was seen. CONCLUSIONS: Women using antidepressants during pregnancy and their newborns have increased pathology. It is not clear how much of this is due to drug use or underlying pathology. Use of TCAs was found to carry a higher risk than other antidepressants and paroxetine seems to be associated with a specific teratogenic property.

Selected neonatal outcomes in dizygotic twins after IVF versus non-IVF pregnancies.

OBJECTIVE: To compare neonatal outcome among twins conceived after in vitro fertilisation (IVF) with that of spontaneously conceived twins. DESIGN: Comparison of different-sex (dizygotic) twins born after IVF with non-IVF dizygotic twins. SETTING: National health registers in Sweden. POPULATION: All births in Sweden during the period 1982-2007. METHODS: We studied gestational duration, lowest birthweight and birthweight difference in the twin pair, presence of one or two twins with a respiratory complication, and with jaundice in one or both twins. Risk estimates were calculated as odds ratios with adjustments for year of birth, maternal age, parity and smoking in pregnancy. MAIN OUTCOME MEASURES: Gestational duration, birth weight, respiratory complications, jaundice. RESULTS: We studied 1545 pairs of dizygotic twins born after IVF, and 8675 pairs of dizygotic twins where IVF was not known to have occurred. The risk for preterm delivery before 32 weeks of gestation was significantly increased among dizygotic twin pairs born after IVF compared with non-IVF dizygotic twin pairs. No significant difference in low birthweight or birthweight difference within twin pairs was seen. There was an increased occurrence of twin pairs with respiratory problems or jaundice, but only the latter diagnosis occurred in a statistically significant excess. CONCLUSIONS: The study confirms recent findings that IVF is associated with an increased risk for some neonatal complications, not only among singletons but also among twins.

Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review.

Degenerative cervical radiculopathy: clinical diagnosis and conservative treatment. A review. To provide a state-of-the-art assessment of diagnosis and non-surgical treatment of degenerative cervical radiculopathy a literature search for studies on epidemiology, diagnosis including electrophysiological examination and imaging studies, and different types of conservative treatment was undertaken. The most common causes of cervical root compression are spondylarthrosis and disc herniation. Diagnosis is made mainly on clinical grounds, although there are no well-defined criteria. Provocative tests like the foraminal compression test are widely used but not properly evaluated. The clinical diagnosis of degenerative cervical radiculopathy can be confirmed by magnetic resonance imaging. The role of electromyography is mainly to rule out other conditions. Cervical radiculopathy is initially treated conservatively, although no treatment modality has been evaluated in a randomized controlled trial. Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review.

Time-space clustering of date at birth in childhood-onset diabetes.

OBJECTIVE: To investigate whether there was a temporal and geographical clustering of time of birth for infants with childhood-onset diabetes. RESEARCH DESIGN AND METHODS: The nationwide Swedish Childhood Diabetes Registry, which ascertains 99% of children with recent-onset diabetes (0-14 years), was linked with the Swedish Medical Birth Registry. Clustering of 3,725 patients as to place and time of birth was studied compared with the general population. For each municipality (and in the three large cities of Sweden for each parish), the observed number of patients was compared with the expected number calculated from the average total rate and the number of births in that municipality. Clustering in time of birth within municipality was analyzed using a modification of a set technique by Chen (14). RESULTS: There was no consistent variability in diabetes risk by calendar birth month, but for specific years, the risk varied during the year. When geographic localization for place of birth was studied on a municipality level, four municipalities showed a statistically significant case excess while one would have been expected by chance. When we looked for clusters in both time and space for date of birth, clearly more clusters than expected were identified (P < 0.01). Of the total of 198 primary clusters, 42 included three or more patients being born in the same municipality within an unlikely short period always < 2 years. CONCLUSIONS: This is the first study indicating a clustering according to place and time of birth for later risk to develop type I diabetes. Such a phenomenon would agree with the hypothesis that infections in early life, including fetal infections, can increase the risk for diabetes.

Thrombectomy in posterior circulation stroke through persistent primitive trigeminal artery: A case report.

We describe a case of intra-arterial treatment (IAT) of acute posterior circulation occlusion in a patient with a persistent primitive trigeminal artery (PPTA). The patient presented with an acute left sided hemiparesis and loss of consciousness (Glasgow coma score of 5). Computed tomography angiography showed an acute occlusion of the right internal carotid artery (ICA), the PPTA, distal basilar artery (BA), right posterior cerebral artery (PCA), and right superior cerebellar artery (SCA). Stent-retriever assisted thrombectomy was not considered possible through the hypoplastic proximal BA. After passage of the proximal ICA occlusion, the right PCA and SCA were recanalized through the PPTA, with a single thrombectomy procedure. Ten days after intervention patient was discharged scoring optimal EMV with only a mild facial and left hand paresis remaining. PPTA is a persistent embryological carotid-basilar connection. Knowledge of existing (embryonic) variants in neurovascular anatomy is essential when planning and performing acute neurointerventional procedures.

Major congenital malformations in Down syndrome.

We studied major malformations in 5,581 infants with Down syndrome (DS) from three registers of congenital malformations. THe prevalence at birth of 23 different malformations was compared with the program-specific rates for each malformation in non-DS infants. An about 300 times risk increase was seen for annular pancreas, cataracts and duodenal atresia and an about 100 times risk increase for megacolon and small choanal atresia. Esophageal, anal and small bowel atresia, preaxial polydactyly, and omphalocele all showed risk increases between 10 and 30 times. Statistically significantly elevated risk ratios around 3-5 were seen for cleft palate, cleft lip/palate, and limb deficiencies. No increased risk was seen for neural tube defects, hydrocephaly, microtia, renal agenesis or severe dysgenesis, hypospadias or polydactyly other than preaxial. Oral clefts were more often present in DS in the Swedish material than in the other two materials. Cardiac defects were registered in 26% of all cases (varying between programs) but 28% of the cardiac defects were unspecified. DS infants born to women younger than 25 years had a significantly increased risk for megacolon and there was a trend increasing risk for esophageal or anal atresia with maternal age. A decreased risk for cardiac defect in DS infants born to teenage mothers was found, quite pronounced for endocardial cushion defects and ventricular septum defects. There were no statistically significant differences in the sex distribution of specific malformations in infants with DS and in non-DS infants.

OEIS complex--a population study.

Using a novel method for the analysis of infants with multiple malformations, we investigated the cluster of associated malformations called the OEIS (omphalocele, bladder exstrophy, imperforate anus, spine defect) complex among 5,260 infants with multiple malformations identified in four large registers of congenital malformations, corresponding to 5.84 million births. The existence of the OEIS complex was clearly demonstrated and malformations entering it could be defined. Other than the four classical malformations, omphalocele, bladder exstrophy, imperforate anus, and spine malformation, a strong association with spina bifida and intersex was stressed. Spine malformations occurred not only in the lumbosacral level but also more cranially, and an association also with upper spina bifida could be demonstrated. No specific association with any other malformation, including cardiac defects, was apparent. The OEIS complex is an unusually clearly defined entity among the various nonrandom associations which have been described.

VATER non-random association of congenital malformations: study based on data from four malformation registers.

This study was undertaken to find a strict, unbiased epidemiological delineation of the VATER non-random association of congenital malformations and, based on registry information, to identify a group of probable VATER association infants suitable for etiological analyses. Information on 5,260 infants with multiple malformations was collected from four large registers of congenital malformations. Data were analyzed using a statistical method in which various putative confounders were controlled for. Our results indicate the existence of a distinct group of malformations corresponding to the VATER association: esophageal atresia, anal atresia, upper preaxial limb reduction defects, and costo-vertebral malformations. A subdivision into an upper and a lower group of VATER association was indicated, with heart malformations associated with the upper group and kidney malformations associated with the lower group. Restricting the inclusion criteria for VATER association to the above mentioned core malformations, few infants seem to belong to the VATER association, thus limiting the possibilities of carrying out etiological analyses. A relatively large number of infants may belong to a family of related conditions among which VATER association is a subgroup. In the search for risk factors, a strict definition of the VATER association is needed in order to not dilute the study material with irrelevant cases. The present study provides such strict inclusion criteria.

Experimental autoimmune encephalomyelitis in hybrids between Lewis and Brown Norway rats.

The susceptibility to experimental autoimmune encephalomyelitis (EAE) in Lewis (Lew) and Brown Norway (BN) rats was studied in breeding experiments, evaluating EAE from clinical signs of the disease. The Lew strain is highly susceptible, the BN strain is resistant to EAE. F1 hybrids between the strains show an intermediate susceptibility as described by earlier authors. Back-cross experiments verify that susceptibility is inherited in a complex way, at least according to a two-gene model previously suggested. Analysis of the F1 hybrids showed a bi-modal distribution of clinical scores, one group of rats which appear to have the same degree of susceptibility as the Lew strain, and another group with very low susceptibility. Study of F2 rats produced by F1 rats with high or low susceptibility showed that this property was probably not inherited, arguing against a residual heterozygosity in the parental strains. As an alternative hypothetical explanation, the possibility of allogeneic exclusion of genes regulating suppression of EAE is discussed.

Diabetes insipidus and use of desmopressin (Minirin) during pregnancy.

With the use of two central health registries in Sweden, the Hospital Discharge Registry and the Medical Birth Registry, we identified 100 infants born of women who had been hospitalized for diabetes insipidus. By checking the medical records of these women, 29 infants were identified whose mothers had diabetes insipidus prior to the pregnancy and had been treated through the pregnancy with desmopressin. These infants had a normal birth weight and gestational length; there was only one congenital malformation identified (a ventricular septum defect with a patent ductus arteriosus and simian lines). This child died at the age of 14 years in a hypophyseal disease. This is the largest material published on desmopressin during pregnancy. The results suggest that maternal diabetes insipidus and treatment with desmopressin during the whole pregnancy does not constitute a major risk for the infant.

Down's syndrome and maternal cancer. A preliminary study.

The possible association between maternal cancer and Down's syndrome was studied in a register-based case-control study of 962 women who had an infant with Down's syndrome born during 1973-1981, and to each two controls, matched for maternal age, parity, and year of delivery. A total of 952 complete triplets was obtained. Among them, 63 Down's syndrome mothers and 79 control mothers were found in a cancer registry for the period 1958-1982 (odds ratio 1.6;95% conf. interval 1.3-2.0). Of these, 14 Down's syndrome mothers and 20 controls had malignant lesions (odds ratio 1.4, 0.9-2.2), and 49 Down's syndrome mothers and 55 controls had cervical cancer in situ (odds ratio 1.8, 1.4-2.3). This risk increase was present both before and after the delivery of the Down's syndrome infant. Various explanations of these findings are discussed and the need for further data is stressed.

Pregnancy and delivery characteristics of women whose infants develop child cancer. A study based on registry information.

Data on all cancers among children born 1973-1984 were extracted from the Swedish Cancer Registry and linked to data in the Medical Birth Registry (1,268 cancer cases). For each case, two controls were selected, matched for maternal age, parity, county, and month of birth. A marginally increased risk of childhood malignancy was seen in the offspring of teenage mothers and at parity 1 and 4+. There was an excess among cases of the diagnosis physiological icterus. No statistically significant associations were found between childhood malignancy and infant sex, twinning, birthweight, non-chromosomal malformations, maternal smoking, or complications during pregnancy.

A women's birth cohort effect on malformation rates.

A relatively sudden increase in prevalence at birth of gastroschisis was seen in Sweden at the beginning of the 1970s. Case-control studies, looking for a teratogenic factor, have proved negative. This paper presents a hypothesis suggesting that the women's birth cohort has an effect: women born in 1953-5 have an increased probability of having this type of malformed infants. A computer simulation is made indicating that the actually recorded facts can, at least in part, be explained by the hypothesis.

The descriptive epidemiology of anophthalmia and microphthalmia.

BACKGROUND: Anophthalmia and microphthalmia are serious eye malformations which recently have been associated with exposure to Benomyl. Data on these malformations are scarce in the literature and reported prevalences at birth vary strongly. METHODS: Data from three large registers of congenital malformations were analysed and comprised 849 malformed infants based on close to 5.7 million births. RESULTS: This is the largest available epidemiological study on anophthalmia and microphthalmia. The prevalence at birth was 1.50 per 10,000, varying between 0.92 and 2.29 between registers but no varying significantly between races in the California register. The variation in rates was mainly due to different inclusion of chromosomally abnormal infants (mainly trisomy 13) and of infants with microphthalmia occurring with major non-eye malformations. On the other hand, rates of anophthalmia and isolated microphthalmia were similar. Other major non-eye malformations were found in 73% of infants without a known chromosome anomaly. The malformation was bilateral in 53-60% of infants except when microphthalmia existed without any other malformations when only 27% were bilateral. Sex distribution was normal, there was a slight excess of twins, and an increased risk at high maternal age. CONCLUSIONS: In analytical studies searching for the cause of these malformations, it may be useful to restrict the analysis to infants with anophthalmia or isolated microphthalmia as the recording of such cases seems to be more reliable than of microphthalmia occurring with other malformations. The conclusions presented in the literature on the possible effect of Benomyl are partly based on data with apparent very incomplete ascertainment.