Effective prevention of post-dural puncture headache with insertion of an intrathecal catheter in parturients: a retrospective study and meta-analysis.

BACKGROUND: Accidental dural puncture is a common complication of labour analgesia. It can trigger post-dural puncture headache, with associated morbidity and increased costs. Intrathecal catheter placement is a prophylactic procedure which can reduce incidence and severity of post-dural puncture headache. METHODS: We conducted a retrospective single-centred study to define incidence and risk factors of accidental dural puncture and post-dural puncture headache in an obstetric population. We also evaluated effectiveness of intrathecal catheter placement compared to epidural catheter replacement in reducing incidence of post-dural puncture headache. We then conducted a systematic review and meta-analysis which included all studies comparing intrathecal catheter placement to epidural catheter replacement in obstetric patients with accidental dural puncture assessing the outcome of reduced incidence of post-dural puncture headache as a dichotomous variable. RESULTS: Accidental dural puncture had an incidence of 0.25% (60 cases). Of these, 66% developed post-dural puncture headache. A total of 77% (47/60) of patients with accidental dural puncture were treated with an intrathecal catheter placement, while 23% (13/60) had an epidural catheter replacement. Incidence of post-dural puncture headache was lower in the intrathecal catheter group (spinal 26/47, 60.5% epidural 11/13, 84.6%), although not reaching statistical significance (RR 0.71, CI 95%: 0.51-1.00; p = 0.049). The meta-analysis revealed that intrathecal catheter placement significantly reduced incidence of post-dural puncture headache compared to epidural catheter replacement (pooled RR 0.81, 95% CI 0.72-0.91, p < 0.001). CONCLUSIONS: Intrathecal catheter placement is a promising measure to prevent post-dural puncture headache, especially if followed by a pain management protocol and a continuous saline infusion.

Transcriptomic and cellular decoding of functional brain connectivity changes reveal regional brain vulnerability to pro- and anti-inflammatory therapies.

BACKGROUND: Systemic inflammation induces acute changes in mood, motivation and cognition that closely resemble those observed in depressed individuals. However, the mechanistic pathways linking peripheral inflammation to depression-like psychopathology via intermediate effects on brain function remain incompletely understood. METHODS: We combined data from 30 patients initiating interferon-α treatment for Hepatitis-C and 20 anti-tumour necrosis factor (TNF) therapy for inflammatory arthritis and used resting-state functional magnetic resonance imaging to investigate acute effects of each treatment on regional global brain connectivity (GBC). We leveraged transcriptomic data from the Allen Human Brain Atlas to uncover potential biological and cellular pathways underpinning regional vulnerability to GBC changes induced by each treatment. RESULTS: Interferon-α and anti-TNF therapies both produced differential small-to-medium sized decreases in regional GBC. However, these were observed within distinct brain regions and the regional patterns of GBC changes induced by each treatment did not correlate suggesting independent underlying processes. Further, the spatial distribution of these differential GBC decreases could be captured by multivariate patterns of constitutive regional expression of genes respectively related to: i) neuroinflammation and glial cells; and ii) glutamatergic neurotransmission and neurons. The extent to which each participant expressed patterns of GBC changes aligning with these patterns of transcriptomic vulnerability also correlated with both acute treatment-induced changes in interleukin-6 (IL-6) and, for Interferon-α, longer-term treatment-associated changes in depressive symptoms. CONCLUSIONS: Together, we present two transcriptomic models separately linking regional vulnerability to the acute effects of interferon-α and anti-TNF treatments on brain function to glial neuroinflammation and glutamatergic neurotransmission. These findings generate hypotheses about two potential brain mechanisms through which bidirectional changes in peripheral inflammation may contribute to the development/resolution of psychopathology.

Effects of a Cereal Bar with a Combination of Phytoestrogens on the Climacteric Symptoms: A Placebo-Controlled, Randomized Trial.

OBJECTIVE: This study evaluated whether the consumption of a cereal bar combining different phytoestrogens could contribute to the reduction of climacteric symptoms in women. METHODS: This is a clinical, prospective, randomized, simple-blind trial. Forty-eight women, aged 40-65 years, with climacteric symptoms, from a city in southwestern Paraná, Brazil. Participants were randomly assigned into two groups; Phytoestrogens group (PHY = 24), which received for 90-day period a cereal bar containing 80.73 milligrams of soybean and flaxseed phytoestrogens, and the placebo group (PLA = 24), which consumed rice flakes biscuit. Clinical, sociodemographic and anthropometric data were collected and climacteric symptoms were assessed using the Kupperman Index (KI). RESULTS: Forty-three women were analyzed (PHY = 21 and PLA = 22). There were significant reductions in the overall KI score in both groups at the end of the intervention period (p < 0.05). However, the comparison between the groups using linear regression models presented expressively better symptom improvement in the PHY group -6.43 over time (95% CI: -11.6; -1.26; p < 0.05) KI points, with perimenopausal -15.15 (95% CI: -28.95; -1.35) and postmenopausal women -19.34 (95% CI: -33.68; -4.99) showed considerably greater reductions in symptoms at the end of the intervention period compared to premenopausal women. There was also significant reduction in symptoms of hot flushes, paresthesia, sexual complaints, insomnia and melancholy. CONCLUSION: The consumption of a cereal bar containing phytoestrogens was able to improve the symptoms of climacteric syndrome.

The daily-practiced post-partum hemorrhage management: an Italian multidisciplinary attended protocol.

Postpartum hemorrhage (PPH) is one of the most frequent causes of mortality and morbidity in the obstetric population globally, causing about a quarter of maternal deaths yearly, and is the leading cause of maternal death worldwide. The management of PPH remains a topic of great debate, even in view of new diagnostic and therapeutic possibilities in recent years, for which, however, the body of evidence available thus far is still scarce, as the standard values are lacking. The protocol hereby presented was developed after a literature review and during several meetings of an Italian multidisciplinary task group of specialists adopting a modified Delphi method, and is the result of the synthesis of therapeutic operational protocols for the treatment of PPH applied by the different specialties within the team. This protocol is intended to represent a practical proposal to support clinicians in the management of a particularly complex event that requires the intervention of a multidisciplinary team and the implementation of dedicated management protocols.

Glutamate and multiple sclerosis.

Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting oligodendrocytes with sparing of axons until advanced stages of the disease. For this reason, most of the earliest experimental studies focused on the role of cytokines and chemokines at the site of oligodendrocytes loss and on the importance in MS pathogenesis of classical inflammatory mechanisms. As a result, several attempts to treat MS through reduction of the local inflammatory milieau have been performed, leading to the current "immunomodulatory" treatment of the disease. However, more recently the importance of axonal loss and neurodegeneration even in the earliest stages of MS has been also recognized, and additional or concomitant players have been therefore searched. Evidence is now increasing that excessive glutamate is released at the site of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating leukocytes and activated microglia. These observations are no longer simply preclinical results obtained in the MS animal model, i.e. experimental allergic encephalomyelitis, but have already been partially confirmed by post-mortem studies and in vivo analysis in MS patients, thus raising the possibility that modulation of glutamate release and transport as well as receptors blockade might be relevant targets for the development of future therapeutic interventions.

Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy.

BACKGROUND: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. METHODS: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. RESULTS: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory-like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. CONCLUSIONS: The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.

The maternal cardiovascular effect of carbetocin compared to oxytocin in women undergoing caesarean section.

OBJECTIVE: To compare haemodynamic changes, measured noninvasively using the USCOM monitor, after combined spino-epidural anaesthesia and after administration of two different uterotonic drugs, oxytocin and carbetocin, in a population of pregnant women during elective caesarean delivery. METHODS: Haemodynamic measurements were obtained with the USCOM system, by positioning a probe at maternal suprasternal notch (SSN) until the aortic valve flow's profile was optimally identified. Evaluations of the haemodynamic profile were obtained in seven different moments: before anaesthesia; during skin incision; 60, 180 and 300s after administration of uterotonic drug, at closure of the uterus, at closure of the skin. Doses of uterotonic drugs were: Oxytocin 5UI in 500cc NaCl eV, Carbetocin 100mcg in bolus eV. Main measured parameters were: heart rate, mean blood pressure, stroke volume, cardiac output and total vascular resistance. RESULTS: We enrolled 32 pregnant women. Patients were randomized in two groups: oxytocin and carbetocin. A reduction in mean blood pressure, a reduction of total vascular resistance and an increase of cardiac output and of stroke volume were seen, while heart rate values remained stable in both treatment groups. No statistically significant differences were found. DISCUSSION: Administration of carbetocin is associated with a substantial global haemodynamic stability in patients undergoing elective caesarean section without any difference with oxytocin. This observation allows us to consider carbetocin comparable to oxytocin, with minimum haemodynamic impact on the maternal circulation. This minimal effect on global haemodynamic stability might extend the use of this uterotonic drug in patients at high haemorrhagic risk with preeclampsia.

Intrapartum sonography for occiput posterior detection in early low dose combined spinal epidural analgesia by sufentanil and ropivacaine.

AIM: To evaluate the incidence of occiput posterior position in labour with and without combined spinal epidural analgesia (CSE) by low dose of sufentanyl and ropivacaine. MATERIAL AND METHODS: This study focused on 132 women subdivided in two groups, patients in spontaneous and in labour analgesia, administered by a low dose CSE by sufentanyl and ropivacaine; all women were evaluated by digital examinations and ultrasound till delivery. All data were collected and analyzed by an independent reviewer. RESULTS: In the second stage, 79 were persistent occiput posterior position (POPP) fetuses and 36 were translated from anterior to posterior position (TAPP) fetuses. Specifically, in spontaneous labour on 25 women in anterior position, there were 17 TAPP and in CSE analgesia on 28 women in anterior, there were 19 in TAPP, without significant differences. The number of asynclitisms was higher in the POPP group (84%) respect to the TAPP group (75%), so as the rate of caesarean section (67% versus 52.7%). CONCLUSIONS: The labour with low dose of ropivacaine and sufentanyl does not increase the occiput posterior position during fetal descent, leading to a POPP. Finally, since in the occiput anterior presentation labour analgesia significantly lengthens time to delivery, in the occiput posterior position this is significantly increased, with a prolonged second stage of labour and reduced time of descent of fetal head in obstetric pelvis.

Cerebrospinal fluid levels of BAFF and APRIL in untreated multiple sclerosis.

OBJECTIVE AND SUBJECTS: To examine in vivo levels of BAFF (B-cell activating factor of the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) in both the cerebrospinal fluid (CSF) and serum of 30 naïve MS patients and 79 subjects affected by acute or chronic inflammatory or non-inflammatory neurological diseases. DESIGN: Case-control study. RESULTS: No difference among groups was evidenced in serum BAFF or APRIL levels. By contrast, CSF levels of BAFF in MS (mean 144.3 pg/ml+/-141.2), although not significantly different from those observed in NIND (164.2 pg/ml+/-92.0), acute peripheral OIND (243.1 pg/ml+/-139.0) or chronic OIND (240.2 pg/ml+/-122.5), were significantly higher in acute central OIND patients (1274.0 pg/ml+/-803.8; p<0.001 vs. all groups). Similarly, CSF APRIL levels in MS (1541.0 pg/ml+/-1071.0), NIND (2629.0 pg/ml+/-1669.0), acute peripheral OIND (2834.0 pg/ml+/-1118.) or chronic OIND (2764.0 pg/ml+/-659.7) were not significantly different, while they were significantly higher in acute central OIND (6218.0 pg/ml+/-3790.0; p<0.001 vs. MS and NIND; and p<0.05 vs. acute peripheral OIND). CONCLUSIONS: Our results strongly suggest that further investigation is warranted to elucidate the role of BAFF and APRIL in MS and that serum levels of BAFF and APRIL do not reflect CSF levels.

Narrowing the window for 'senile chorea': a case with primary antiphospholipid syndrome.

Several apparently idiopathic cases of so called 'senile chorea' have been recently redefined by the availability of brain MRI scan and the clinical introduction of genetic testing for Huntington's disease. Cases currently still regarded as idiopathic might yet be attributed to other medical conditions. Chorea as a unique manifestation of a primary antiphospholipid syndrome (PAPS) has so far been described only in young and middle-aged subjects. Here, we report a typical case of 'senile chorea' associated with PAPS, thus expanding the potential underlying etiologies and further narrowing the window of primary 'senile chorea'.

Isolated bilateral anterior optic neuritis following chickenpox in an immunocompetent adult.

Chickenpox may lead to several different neurological complications, but optic neuritis has rarely been described; in particular, only one case of isolated bilateral anterior optic neuritis (AON) in an immune-competent adult has so far been reported. We describe a second case of this type and consider similarities and differences between our patient and all other cases of AON following chickenpox. Then, we discuss the therapeutic role of steroids and advance the hypothesis of different pathogenetic pathways in immune-competent and immune-compromised subjects.

Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis.

Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure consisting of autologous reinfusion of peripheral blood mononuclear cells (PBMC) after direct exposure to 8-methoxy-psoralen and UV-A. It has been described as a successful treatment for different T-cell-mediated diseases and preliminary results suggest that ECP might be effective in the treatment of relapsing-remitting multiple sclerosis, but does not significantly alter the course of the progressive form of MS. In this study, we report the safety data and some preliminary efficacy evidence obtained using ECP in the treatment of five patients with refractory relapsing-remitting (RR) MS: in most cases ECP induced a reduction in the relapse rate and an EDSS stabilisation, with an apparent general MRI stabilisation. In conclusion, our results confirm ECP safety and tolerability and suggest that this treatment might be useful as a therapeutic alternative in the subgroup of RRMS patients not responsive to or not eligible for traditional immunomodulating or immunosuppressive treatments.

Minimum local anaesthetic dose (MLAD) of intrathecal levobupivacaine and ropivacaine for Caesarean section.

We determined the minimum local anaesthetic dose (MLAD) of spinal levobupivacaine and ropivacaine for Caesarean section. Ninety women were randomly allocated to two groups and received 3 ml of study solution by a combined spinal/epidural technique. The initial dose was 12 mg for levobupivacaine and 17 mg for ropivacaine groups. To be considered effective, a test solution had to achieve a visual analogue pain score (VAPS) of 30 mm or less at skin incision, uterine incision, birth, peritoneal closure, and at the end of surgery. Effective or ineffective responses determined, respectively, a 0.3 mg decrease or increase of the same drug for the next patient in the same group, using up-down sequential allocation. The MLAD of levobupivacaine was 10.58 mg (CI 95%: 10.08-11.09) and the MLAD of ropivacaine 14.22 mg (CI 95%: 13.67-14.77), using the Dixon and Massey formula. The potency ratio between spinal levobupivacaine and spinal ropivacaine was 1.34.

Management of headache in emergency room.

Headache is one of the most common symptoms that leads patients to the emergency room (ER) and is often related to diseases requiring prompt diagnosis and immediate treatment. This consideration brought us to consider the importance of the neurologist in improving the management of patients arriving in the ER with headache. We carried out a study for testing the degree of agreement between ER physician and neurologist using patient evaluation at headache centre (HC) as the gold standard. One hundred and seventeen patients with idiopathic (78) or symptomatic (39) headache were evaluated by the ER physician, the ER neurologist and the HC expert. The ER physician and the HC expert reached a fair agreement (Kappa=0.40); the other two pairs reached a moderate agreement (Kappa=0.57-0.60). There was no significant difference in the agreement of the three evaluators in patients with impairment of daily living activities or aged over 40. The agreement between the ER physician and the neurologist was lower (Kappa=0.58), especially in patients with their first headache episode. Based on our results, patients seen at the ER for a headache episode can be fairly successfully managed by the ER physician, except those who present a first attack, for whom neurological consultation is needed.

MIDAS questionnaire in the emergency setting.

Migraine is a common disorder and is a major cause of disability and loss of working performance in western countries. Therefore, many tools have been developed to assess migraine related disability. Among these, the Migraine Disability Assessment (MIDAS) questionnaire has been shown to be of particular interest, as it is valid, reliable and useful for therapeutic decisions. In this pilot study, we address the validity of the MIDAS questionnaire in an unselected population of migraine patients in the emergency setting. We found that the MIDAS scores in the emergency room were similar to those collected in a specialised headache centre. This result suggests that the MIDAS questionnaire could be reliably used in the emergency setting, hence avoiding unnecessary delays in the treatment of migraine patients.

Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study.

The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalidomide sensory neurotoxicity was found to be cumulative dose dependent but occurs only when the total dose is relatively high (>20 g). The risk of developing sensory neuropathy is around 10% below this threshold but increases with higher doses.

Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.

Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell proliferation tests of human and rodents cells evidenced that pixantrone was effective at concentrations which can be effectively obtained after i.v. administration in humans. Cardiotoxicity was present only in MTX-treated rats. The effectiveness and the favorable safety profile makes pixantrone a most promising immunosuppressant agent for clinical use in multiple sclerosis (MS).