Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy

The primary aim of this study was to assess the risks of fetal growth restriction and birth defects in children exposed prenatally to newer and older antiepileptic drugs, using an unselected epilepsy cohort. Deliveries recorded in the compulsory Medical Birth Registry of Norway 1999–2011 formed the study population. All 2,600 children exposed to antiepileptic drugs during pregnancy were compared to all 771,412 unexposed children born to women without epilepsy. Children of untreated mothers with epilepsy served as an internal control group. The main outcomes were small for gestational age birth weight and head circumference, and major congenital malformations. Children exposed to antiepileptic drugs had a moderate risk of growth restriction. Infants exposed to topiramate had a considerable risk of microcephaly (11.4 vs. 2.4 %; OR 4.8; CI 2.5–9.3) and small for gestational age birth weight (24.4 vs. 8.9 %; OR 3.1; 95 % CI 1.9–5.3). Carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, gabapentin, and pregabalin had low malformation rates, whereas topiramate tended to have an elevated malformation rate. Valproate monotherapy was associated with a significant risk of birth defects (6.3 vs. 2.9 %; OR 2.5; CI 1.6–3.8), and specifically with septal heart defects and hypospadias. For mothers using valproate, the presence of major birth defect in one child was associated with a markedly increased risk for the siblings (42.9 vs. 6.7 %; OR 10.4; CI 2.3–46.7). Children of untreated mothers with epilepsy had malformation risk similar to the reference group. In conclusion, topiramate was associated with a substantial risk of fetal growth restriction, and possibly an increased malformation rate. Other newer-generation antiepileptic drugs had a low malformation rate. Valproate monotherapy had a significant malformation risk, especially in repeated pregnancies.     

Leukoencephalopathy,cerebral calcifications and cysts: a family study

We present a clinical, neuro-radiological and genetic study on a family with members suffering from an autosomal dominantly inherited syndrome characterised by epilepsy, cerebral calcifications and cysts, bone abnormalities; progressive neuro-cognitive deterioration and paranasal sinusitis. This syndrome shares several features with leukoencephalopathy with calcifications and cysts also called Labrune syndrome and the condition of cerebroretinal microangiopathy with calcifications and cysts (CRMCC; Coats plus syndrome). Genetic studies in this family did not reveal mutations in the CTC1 gene defected in CRMCC. We interpret our results as those supporting recent findings that despite clinical similarities, late-onset Labrune and Coats plus syndrome might be distinct entities. This family may have Labrune syndrome or a yet unclassified entity; exploration of similar cases could help classifying this one, and related conditions.     

Digoxin in heart failure

Digoxin is an agent with a long history of use in the management of heart failure; its benefits have just been quantified in recent years. It has long been known that digoxin provides a small amount of inotropic augmentation; however, it is now realized that digoxin also modulates the neurohormonal activation that occurs in heart failure. Although long-term therapy with digoxin does not decrease mortality, it does provide clinical benefit in terms of improved exercise tolerance and decreased hospitalizations across all severities of heart failure. Serum concentrations of digoxin associated with clinical benefits are lower than previously recognized (0.8-1.0 ng/mL). Digoxin toxicity can be easily avoided by maintaining these relatively low serum concentrations, avoiding and aggressively treating hypokalemia, and being mindful of poor renal function and drug interactions that may result in digoxin accumulation.     

Changes in delusions in the early phase of antipsychotic treatment – An experience sampling study

It has been suggested that different aspects of delusions (conviction, distress, preoccupation) respond to treatment at different rates, and that the cognitive bias of ‘Jumping to Conclusions’ (JTC) may predict treatment outcome. This study investigates changes in delusion dimensions using Experience Sampling Methodology (ESM) and the role of JTC as a predictor of change during the initial 2 weeks of antipsychotic treatment on admission to hospital. Sixteen acute patients with delusions were assessed seven times per day for 14 days using computerised ESM. ESM assessed moment-by-moment experiences of affect, psychotic symptoms, and delusion dimensions. Clinical ratings were completed at baseline, 1 week and 2 weeks later. The 'beads' task was used to measure JTC at baseline. Delusion dimensions improved over the two weeks of antipsychotic treatment and admission to hospital. Different delusional dimensions changed at different rates, with distress and disruption being more responsive than conviction and preoccupation on both PSYRATS and ESM ratings. Eight out of 16 participants showed a JTC bias on the beads task at baseline. Exploratory analyses showed that JTC predicted changes in the ESM ratings of delusion conviction and distress, suggesting that reasoning biases may predict treatment response.     

Perioperative Breast MRI Is Not Associated with Lower Locoregional Recurrence Rates in DCIS Patients Treated With or Without Radiation

Introduction

For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT).

Methods

A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis.

Results

There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79–1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78–2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86).

Conclusions

We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.     

Significance of perivesical lymph nodes in radical cystectomy for bladder cancer

ObjectiveThe location of positive lymph nodes (LNs) is important for bladder cancer staging. Little is known regarding the impact of perivesical (PV) lymph node (PVLN) involvement on survival. This study characterized PVLN identified after radical cystectomy (RC) and analyzed their impact on recurrence and survival.Materials and methodsWe reviewed our institutional review board–approved database including all patients who underwent RC with pelvic lymphadenectomy for curative intent for urothelial carcinoma. Clinical and pathologic data were obtained. Patients were analyzed in groups according to the location of positive LNs: PV+/other LN (ON)+, PV+/ON?, and PV?/ON+. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox regression (including pathologic T category, number of positive LNs, highest level of positive LNs, chemotherapy, and margin status) was performed to evaluate associations between PVLN status and survival.ResultsIn total, 2,017 patients met inclusion criteria and 465 (23%) were LN+. PVLNs were identified in 936 patients (47%), positive in 197 patients (10%), and represented isolated LN+disease in 101 patients (5%). On univariate analysis, RFS and OS were significantly worse in the PV+/ON+group compared with the PV+/ON? and PV?/ON+ groups. There were no significant differences in RFS or OS between the PV+/ON? and PV?/ON+ groups. On multivariable analysis, PV+/ON+disease was independently associated with worse RFS and OS when compared with PV?/ON+ disease.ConclusionsPVLNs were identified in a significant number of patients after RC. Positive PVLN, when in combination with other positive LNs, portends worse survival even when correcting for the number of positive nodes.     

Isolated Tumor Cells in Sentinel Lymph Nodes of Invasive Breast Cancer: Cell Displacement or Metastasis?

The goal of this study was to determine whether the presence of isolated tumoral cells (ITCs) in sentinel lymph nodes (SLNs) after core needle biopsy (CNB) is related to the time interval between CNB and surgery and to histopathologic features of invasive breast cancer. Data from 633 consecutive patients with no micrometastasis or metastasis on both frozen sections and definitive pathologic examination of SLNs were retrieved from a prospective data base. No association was found between ITCs and the time interval between CNB and SLNB. The association was significant with tumor size, the tumor lymphovascular invasion (LVI) and the histologic type of the tumor. This study adds supplementary data to the association between tumoral LVI and ITCs in SLNs, The time interval between CNB procedure and SLNB was not related to affect presence of ITCs, which might not suggest the iatrogenic origin of these cells.     

Unilateral posterior cervical spinal cord infarction due to spontaneous vertebral artery dissection

Context

Ischemia of the cervical spinal cord is a rare complication of spontaneous vertebral artery dissection (VAD) and usually involves the ventral portion. We describe a less evocative clinical presentation and images of unilateral posterior spinal cord infarction due to spontaneous VAD in order to facilitate early diagnosis.

Findings

A previously fit 30-year-old man presented with persistent headaches and proximal motor deficit of the right arm. He was diagnosed with spontaneous dissection of both vertebral arteries, with occlusion of the right one, and the right carotid artery. Neurological examination also revealed a right C2–C3 tactile sensory loss, with unilateral proprioceptive deficit below. Brain images revealed small bilateral cerebellar infarcts which could not be responsible for the clinical symptoms. Magnetic resonance imaging of the spinal cord showed a right posterior cervical spinal cord infarction. The patient achieved nearly complete recovery after several weeks of anticoagulation and rehabilitation.

Conclusion and clinical relevance

Infarction of the caudal portion of the cervical spinal cord, especially unilateral, caused by spontaneous VAD, has rarely been described and is certainly under-diagnosed due to less suggestive symptoms, like unilateral and mainly sensory deficit. Nevertheless, early diagnosis of this condition is important to guide patient management and rehabilitation.