Cocaine-related cervical spinal cord infarction: a case report and review of the literature

Study design Case report. Objectives To report a clinical case of spinal cord infarction due to cocaine use. Setting Spinal Center, IRCCS Fondazione S. Lucia, Rome (Italy). Case presentation Two days after recreational use of cocaine, a 27-year-old Caucasic man was admitted to the emergency department for acute cervical pain, weakness in all four limbs, and urinary retention. A cervical spinal magnetic resonance imaging scan, performed after 2 days, showed a "pencil-like" lesion extending from C4 to T1 metamer, compatible with acute ischemia in the anterior spinal artery territory. Other causes of vascular disorders, as well as inflammatory and infectious disorders were ruled out. At admission in our department, the patient had an incomplete tetraplegia at level C6, an indwelling catheter, and was unable to stand and walk. After 3 months of rehabilitation, he had an AIS score D tetraplegia at level C7, was able to stand and walk using parallel bars, and indwelling catheter was replaced by intermittent catheterization. Discussion and conclusions The etiology of medullary infarction may remain unexplained in nearly 30-40% of cases. Even if rare, cocaine-induced ischemic myelopathy should be considered and ruled out in the differential diagnosis of any acute nontraumatic myelopathy, especially in young patients

Caesarean section on maternal request: an Italian comparative study on patients’ characteristics, pregnancy outcomes and guidelines overview

In recent years, the rate of caesarean sections has risen all over the world. Accordingly, efforts are being made worldwide to understand this trend and to counteract it effectively. Several factors have been identified as contributing to the selection of caesarean section (CS), especially an obstetricians’ beliefs, attitudes and clinical practices. However, relatively few studies have been conducted to understand the mechanisms involved, to explore influencing factors and to clearly define the risks associated with the caesarean section on maternal request (CSMR). This comparative study was conducted to elucidate the factors influencing the choice of CSMR, as well as to compare the associated risks of CSMR to CS for breech presentation among Italian women. From 2015 to 2018, a total of 2348 women gave birth by caesarean section, of which 8.60% (202 women) chose a CSMR. We found that high educational attainment, use of assisted reproductive technology, previous operative deliveries and miscarriages within the obstetric history could be positively correlated with the choice of CSMR in a statistically significant way. This trend was not confirmed when the population was stratified based on patients’ characteristics, obstetric complications and gestational age. Finally, no major complications were found in patients that underwent CSMR. We believe that it is essential to evaluate patients on a case-by-case basis. It is essential to understand the personal experience, to explain the knowledge available on the subject and to ensure a full understanding of the risks and benefits of the medical practice to guarantee the patients not only their best scientific preparation but also human understanding

Neural substrates of motor and cognitive dysfunctions in SCA2 patients: a network based statistics analysis

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome, which can be isolated or associated with extracerebellar signs. It has been shown that patients affected by SCA2 present also cognitive impairments and psychiatric symptoms. The cerebellum is known to modulate cortical activity and to contribute to distinct functional networks related to higher-level functions beyond motor control. It is therefore conceivable that one or more networks, rather than isolated regions, may be dysfunctional in cerebellar degenerative diseases and that an abnormal connectivity within specific cerebello-cortical regions might explain the widespread deficits typically observed in patients. In the present study, the network-based statistics (NBS) approach was used to assess differences in functional connectivity between specific cerebellar and erebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes

Microstructural MRI basis of the cognitive functions in patients with Spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum. The particular atrophy pattern results in some typical clinical features mainly including motor deficits. In addition, the presence of cognitive impairments, involving language, visuospatial and executive functions, has been also shown in SCA2 patients and it is now widely accepted as a feature of the disease. The aim of the study is to investigate the microstructural patterns and the anatomo-functional substrate that could account for the cognitive symptomatology observed in SCA2 patients. In the present study, diffusion tensor imaging (DTI) based-tractography was performed to map the main cerebellar white matter (WM) bundles, such as Middle and Superior Cerebellar Peduncles, connecting cerebellum with higher order cerebral regions. Damage-related diffusivity measures were used to determine the pattern of pathological changes of cerebellar WM microstructure in patients affected by SCA2 and correlated with the patients' cognitive scores. Our results provide the first evidence that WM diffusivity is altered in the presence of the cerebellar cortical degeneration associated with SCA2 thus resulting in a cerebello-cerebral dysregulation that may account for the specificity of cognitive symptomatology observed in patients

Endometriosis and pregnancy. a single institution experience

Endometriosis may compromise the physiological course of pregnancy. The aim of this prospective observational study was to evaluate whether endometriosis causes a higher prevalence of obstetric and neonatal complications as well as a higher risk of caesarean section and to detect a possible correlation between the presence, type, and location of endometriosis and obstetric complications, previous surgery, and pregnancy outcome, as well as the influence of pregnancy on the course of the disease. We compared two cohorts of women with spontaneous pregnancy, with and without endometriosis. Obstetric and neonatal outcomes, mode of delivery, presence, type, and location of endometriotic lesions and the effect of pregnancy on the disease were analyzed. A total of 425 pregnancies were evaluated: 145 cases and 280 controls. Patients with endometriosis showed a higher incidence of miscarriage, threatened miscarriage, threatened preterm labor, preterm delivery, placental abruption, and a higher incidence of caesarean section. A significant correlation with pregnancy-induced hypertension and preeclampsia was found in the presence of adenomyosis. No difference in fetal outcome was found. One case of hemoperitoneum during pregnancy was observed. Pregnancy in women with endometriosis carries a higher risk of obstetric complications, such as miscarriage, threatened miscarriage, preterm labor, preterm birth, and a higher caesarean section rate. Endometriosis does not seem to influence fetal well-being

The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer

Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches

The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons

Background: Although neuronal extracellular sensing is emerging as crucial for brain wiring and therefore plasticity, little is known about these processes in neurodevelopmental disorders. Ubiquitin protein ligase E3A (UBE3A) plays a key role in neurodevelopment. Lack of UBE3A leads to Angelman syndrome (AS), while its increase is among the most prevalent genetic causes of autism (e.g., Dup15q syndrome). By using microstructured substrates that can induce specific directional stimuli in cells, we previously found deficient topographical contact guidance in AS neurons, which was linked to a dysregulated activation of the focal adhesion pathway. Methods: Here, we study axon and dendrite contact guidance and neuronal morphological features of wild-type, AS, and UBE3A-overexpressing neurons (Dup15q autism model) on micrograting substrates, with the aim to clarify the role of UBE3A in neuronal guidance. Results: We found that loss of axonal contact guidance is specific for AS neurons while UBE3A overexpression does not affect neuronal directional polarization along microgratings. Deficits at the level of axonal branching, growth cone orientation and actin fiber content, focal adhesion (FA) effectors, and actin fiber-binding proteins were observed in AS neurons. We tested different rescue strategies for restoring correct topographical guidance in AS neurons on microgratings, by either UBE3A protein re-expression or by pharmacological treatments acting on cytoskeleton contractility. Nocodazole, a drug that depolymerizes microtubules and increases cell contractility, rescued AS axonal alignment to the gratings by partially restoring focal adhesion pathway activation. Surprisingly, UBE3A re-expression only resulted in partial rescue of the phenotype. Conclusions: We identified a specific in vitro deficit in axonal topographical guidance due selectively to the loss of UBE3A, and we further demonstrate that this defective guidance can be rescued to a certain extent by pharmacological or genetic treatment strategies. Overall, cytoskeleton dynamics emerge as important partners in UBE3A-mediated contact guidance responses. These results support the view that UBE3A-related deficits in early neuronal morphogenesis may lead to defective neuronal connectivity and plasticity

RECURRENT PREGNANCY LOSS IS ASSSOCIATED TO LEAKY GUT: A NOVEL PATHOGENIC MODEL OF ENDOMETRIUM INFLAMMATION ?

Background: Recurrent pregnancy loss (RPL) occurs in 3\u20135% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1\u3b2 and IL-18 by ELISA, respectively. Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS (P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1\u3b2 was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women. Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome