Neuropsychiatric adverse events of antiepileptic drugs in brain tumour-related epilepsy: an Italian multicentre prospective observational study.

BACKGROUND AND PURPOSE: We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE). METHODS: This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months. RESULTS: Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs. CONCLUSIONS: Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Evaluation of risk of symptomatic cytomegalovirus reactivation in myeloma patients treated with tandem autologous stem cell transplantation and novel agents: a single-institution study.

The introduction of proteasome inhibitors and/or immunomodulators in the treatment of myeloma has led to an increase in viral infections, particularly in the Herpesviridae family. Previous studies about the risk of cytomegalovirus (CMV) reactivation after autologous stem cell transplantation (ASCT) have examined the clinical outcome after the first ASCT; however, only 1 study to date has investigated the risk of CMV reactivation after a second transplantation. To address this issue, we performed a retrospective chart review on 78 consecutive myeloma patients (median age 56 years) who underwent a tandem non-CD34(+) selected ASCT after induction treatment with either conventional chemotherapy (n = 42) or with novel agents (n = 36), respectively. All subjects had been mobilized and conditioned with cyclophosphamide plus granulocyte colony-stimulating factor and melphalan alone, respectively. CMV DNA load in the blood has been determined by polymerase chain reaction in the case of a clinical suspicion of CMV reactivation; therefore, routine monitoring was not performed. Considering the outcome of both the first and the second transplantations, we observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in 12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8, 12%) experienced a CMV reactivation after the second transplantation. Conversely, 4 CMV reactivations (6%) were observed after the second transplantation in the group of 70 patients who did not experience a CMV reactivation after the first ASCT. No statistically significant difference was observed between first and second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that a pre-transplant treatment with novel agents was the only baseline factor significantly associated with the occurrence of post-ASCT CMV symptomatic reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR: 5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary infection was documented. Our data suggest that second transplantation does not increase the risk of CMV reactivation in our patient population, when compared with the first one, and confirm the role of a pre-transplant treatment with novel agents as a risk factor for CMV symptomatic reactivation.

Buccal Alveolar Bone changes and upper first molar displacement after maxillary expansion with RME, Ni-Ti leaf springs expander and Tooth- Bone-borne Expander. A CBCT based analysis.

AIM: To evaluate the buccal alveolar bone changes and the upper first molar displacement in subjects treated with conventional rapid maxillary expansion (RME), Ni-Ti leaf springs expander (Leaf Expander) and Tooth-Bone-borne Expander (Hybrid Expander) using CBCT scans. METHODS: The sample consisted of 52 children treated with RME (n=18), Leaf Expander (n= 17) and Hybrid Expander (n= 17). CBCTs were taken before and after maxillary expansion and the Horos software was used for the analysis. Descriptive statistics and paired t-test were used to assess changes between the pre-treatment and post-treatment measurements. ANOVA test and Tukey's post hoc test with Bonferroni correction was used for between groups comparison. CONCLUSION: The Hybrid Expander during preadolescence showed few advantages over the use of tooth-anchored expanders. An expansion approach with mini-screws is not preferable during early mixed dentition to a conventional approach. The differences in dental tipping values were clinically insignificant and the reduction in cortical bone thickness remained less than 1 mm. When possible, the use of second primary molars as anchorage should be preferred.

Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: open-label pilot study for assessing the efficacy, tolerability and impact on quality of life.

We conducted a prospective, observational study to verify the efficacy, tolerability and impact on quality of life, mood and global neurocognitive performances of oxcarbazepine monotherapy in patients with brain tumor-related epilepsy (BTRE). Patients were followed for 12 months. We recruited 25 patients (11 females 14 males; mean age 49.7) affected with BTRE (17 de novo patients and 7 in monotherapy with other antiepileptics) and introduced oxcarbazepine monotherapy because of uncontrolled seizures and/or side effects. At first visit, patients underwent neurological examination, Qolie 31P V2, EORTC QLQC30, Zung self-depression rating scale (ZSDRS) and adverse events profile. A seizure diary was given to each patient. Follow-up duration was 1-12 months (mean 7.1 months, 5 patients died and 10 dropped out). Totals of 16 patients underwent both chemotherapy and radiotherapy, 4 chemotherapy only, 1 radiotherapy only, and 4 did not undergo any systemic therapy. Mean dosage of oxcarbazepine was 1,230 mg/day (min 600, max 2,100 mg/day). McNemar's test showed a significant difference in seizure freedom rate (P = 0.002) between baseline and final follow-up in the intent-to-treat population. Six patients (24%) had serious side effects and one patient (4%) mild. Logistic regression revealed that, in our study, chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure outcome (P = 0.658). The test evaluation at final follow-up showed a significant improvement in ZSDRS (P = 0.011) and no change over time. Oxcarbazepine seems to be efficacious in controlling seizures and in improving mood in patients with BTRE, but special caution should be taken when it is administered during radiotherapy.

Trigeminal neuralgia as unusual isolated symptom of fungal paranasal sinusitis in patients with haematological malignancies.

A sinonasal infection is a frequent complication in patients with haematological malignancies, and may represent a challenge in terms of differential diagnosis between a bacterial or fungal infective process and tumour localization. A timely and correct diagnosis in these patients is critical and, therefore, may require consultation of specialists outside of haematology; an incorrect diagnosis which underestimates the seriousness of the infection can be fatal. Symptomatic trigeminal neuralgia resulting from direct compression or perineural invasion from malignancy is not uncommon in the literature. However, trigeminal neuralgia as an isolated symptom at the onset of a bacterial or invasive fungal sinusitis is rare and risks going unnoticed. The authors herein describe three cases of patients affected by acute myeloid leukaemia or lymphoma in which an invasive fungal sinusitis appeared at the onset as an isolated trigeminal neuralgia, with pain located along the distribution area of the second branch of the trigeminal nerve. Only after referring these patients to a neurologist for a host of neurological exams it was possible to confirm a diagnosis of secondary maxillary sinus fungal involvement.

In situ electroporation of mammalian cells through SiO2 thin film capacitive microelectrodes.

Electroporation is a widely used non-viral technique for the delivery of molecules, including nucleic acids, into cells. Recently, electronic microsystems that miniaturize the electroporation machinery have been developed as a new tool for genetic manipulation of cells in vitro, by integrating metal microelectrodes in the culture substrate and enabling electroporation in-situ. We report that non-faradic SiO2 thin film-insulated microelectrodes can be used for reliable and spatially selective in-situ electroporation of mammalian cells. CHO-K1 and SH-SY5Y cell lines and primary neuronal cultures were electroporated by application of short and low amplitude voltage transients leading to cell electroporation by capacitive currents. We demonstrate reliable delivery of DNA plasmids and exogenous gene expression, accompanied by high spatial selectivity and cell viability, even with differentiated neurons. Finally, we show that SiO2 thin film-insulated microelectrodes support a double and serial transfection of the targeted cells.

Mechanical and electrophysiological properties of the sarcolemma of muscle fibers in two murine models of muscle dystrophy: col6a1-/- and mdx.

This study aimed to analyse the sarcolemma of Col6a1-/- fibers in comparison with wild type and mdx fibers, taken as positive control in view of the known structural and functional alterations of their membranes. Structural and mechanical properties were studied in single muscle fibers prepared from FDB muscle using atomic force microscopy (AFM) and conventional electrophysiological techniques to measure ionic conductance and capacitance. While the sarcolemma topography was preserved in both types of dystrophic fibers, membrane elasticity was significantly reduced in Col6a1-/- and increased in mdx fibers. In the membrane of Col6a1-/- fibers ionic conductance was increased likely due to an increased leakage, whereas capacitance was reduced, and the action potential (ap) depolarization rate was reduced. The picture emerging from experiments on fibers in culture was consistent with that obtained on intact freshly dissected muscle. Mdx fibers in culture showed a reduction of both membrane conductance and capacitance. In contrast, in mdx intact FDB muscle resting conductance was increased while resting potential and ap depolarization rate were reduced, likely indicating the presence of a consistent population of severely altered fibers which disappear during the culture preparation.

Antiepileptics in brain metastases: safety, efficacy and impact on life expectancy.

The aim of the study was to evaluate efficacy, safety and impact on life expectancy of levetiracetam (LEV), oxcarbazepine (OXC) and topiramate (TPM) monotherapy in patients with seizures related to brain metastases. We conducted a prospective observational study on 70 patients with brain metastases. Thirteen patients were excluded because they were in prophylactic therapy with antiepileptics, nine patients did not return to our Center. A total of 48 patients with epilepsy related to brain metastases were enrolled. Patients were treated with LEV, OXC and TPM in monotherapy and followed until their death. Eighteen patients dropped out. Therefore, we followed 30 patients. Mean duration of follow-up was 6.1 months. Upon visiting the patients prior to their death (i.e. last visit preceding the death of the patients), we observed a significant reduction (P < 0.001) in the mean monthly seizure frequency; with 19 patients (63.3%) obtaining complete seizure control in the whole population. A significant improvement of seizure frequency was also observed considering each antiepileptic treatment group separately. Median survival time was similar among the three groups of patients and was similar to Class I of prognostic factors of Radiation Therapy Oncology Group. Logistic regression showed that systemic treatments did not influence the antiepileptics' efficacy on seizure control (P = 0.614). In conclusion, regarding the use of newer antiepileptics in patients with seizures related to brain metastases, our data indicate that LEV, OXC and TPM significantly reduce seizure frequency (independently of systemic treatment), produce few side effects and appear not to affect life expectancy.

Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report.

BACKGROUND: Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). AIM OF THE STUDY: To evaluate efficacy and tolerability of ZNS as add-on in BTRE. METHODS: We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. RESULTS: Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. CONCLUSIONS: Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.

Tuberculosis screening in outpatient healthcare workers: lessons from a high-income, low TB burden country.

SETTING: Early diagnosis of latent tuberculous infection (LTBI) should be pursued in healthcare workers (HCWs). While HCWs in hospitals are screened for LTBI, HCWs in outpatient settings are usually not. In 2017, in Italy, a tuberculosis (TB) infected paediatrician working in an outpatient vaccination service infected 15 adults and nine children. The investigation involved 2490 children and 151 adults. Among children, nine were tuberculin skin test-positive, and four developed active TB. Among 123 adult contacts with longer exposure, seven were interferon-gamma release assay (IGRA) positive and none had active TB. Among 28 close contacts, eight had a positive IGRA, and three had pulmonary TB. The total outbreak cost €1 017 903.OBJECTIVE: To compare the outbreak cost with those of potential screening programme strategies.RESULTS: Regular screening of paediatric outpatient HCWs would have cost between €2592 and €11 373. Extending the screening to all outpatient HCWs (caring for adults and children) would have cost between €66 384 and €155 043. Investigating only close contacts would have cost €42 857.CONCLUSION: Each of these screening strategies would have been cost-effective compared with the outbreak investigation occurring in real life with a cut-off of 474 for the maximum number of tested outpatient HCWs needed for the screening strategy to be cost-saving.

A potential role for the vanilloid receptor TRPV1 in the therapeutic effect of curcumin in dinitrobenzene sulphonic acid-induced colitis in mice.

A protective role of the transient potential vanilloid receptor 1 (TRPV1) in intestinal inflammation induced by dinitrobenzene sulphonic acid (DNBS) has been recently demonstrated. Curcumin, the major active component of turmeric, is also able to prevent and ameliorate the severity of the damage in DNBS-induced colitis. We evaluated the possibility that curcumin (45 mg kg(-1) day p.o. for 2 days before and 5 days after the induction of colitis) was able to reduce DNBS-induced colitis in mice, by acting as a TRPV1 agonist. Macroscopic damage score, histological damage score and colonic myeloperoxidase (MPO) activity were significantly lower (by 71%, 65% and 73%, respectively; P < 0.01), in animals treated with curcumin compared with untreated animals. Capsazepine (30 mg kg(-1), i.p.), a TRPV1 receptor antagonist, completely abolished the protective effects of curcumin. To extend these data in vitro, Xenopus oocytes expressing rat TRPV1 were examined. Capsaicin-evoked currents (3.3 micromol L(-1)) disappeared subsequent either to removal of the agonist or subsequent to the addition of capsazepine. However, curcumin (30 micromol L(-1)) was ineffective both as regard direct modification of cell membrane currents and as regard interference with capsaicin-mediated effects. As sensitization of the TRPV1 receptor by mediators of inflammation in damaged tissues has been shown previously, our results suggest that in inflamed, but not in normal tissue, curcumin can interact with the TRPV1 receptor to mediate its protective action in DNBS-induced colitis.

Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease.

A total of 277 patients with untreated Hodgkin's disease, clinical stages I-II, were randomized to cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) alone for 6 monthly cycles or to CVPP plus radiation therapy (RT), 3,000 rad, to involved areas (CVPP plus RT). One or more of the following factors were considered as unfavorable prognosis: age greater than 45 years, more than two lymph node areas involved, or bulky disease. In the favorable group, disease-free survival (77% vs. 70%) or overall survival (92% vs. 91%) at 84 months for CVPP versus RT plus CVPP was similar. Patients with unfavorable prognosis treated with RT plus CVPP had longer disease-free survival (75% vs. 34%) (P = .001) and overall survival (84% vs. 66%) than patients treated with CVPP alone.

The economical efficiency of classic and no-tillage system at genetical modified soybean in conditions of Romania.

The technology of maize without plough land possible to apply in USA and other countries with advanced agriculture, only by atrazine and simazine herbicides synthesis by J. Geigy Company from Switzerland Phillips and Young (1973) said in their book that in USA is practicing no-tillage system on millions acres. After recently dates published by Derpsh (2001) in USA no-tillage is practice on 21,120,000 ha, in Brazil on 14,330,000 ha, in Argentina 10,500,000 ha etc. The chernozem soil in Romania is very properly for no-tillage system. First experiments with no-tillage system have been since 1965 at maize, and at soybean since 2002 until 2005, obtaining remarkable results concerning maize and soybean yields. At genetically modified soybean crop the economic efficiency is very big because fuel consumption was 75 l/ha at classic system and only 21 l/ha at no-tillage system. The expenses with mechanical working were 217 Euro/ha at classic system and only 45 Euro/ha at no-tillage system.

Supportive therapy in neuro-oncology.

Patients with cerebral neoplasms often report pain or other kinds of symptoms which, even though not directly connected to the disease itself, can cause complications in the approach to therapy and worsen the quality of life of the patients. The therapies aimed at controlling these kinds of disturbances are referred to as supportive therapies as they do not cure the underlying disease. However, these therapies should not be underestimated, because, by controlling these disturbances, they are able not only to greatly improve the quality of life of the neuro-oncologic patients but also increase their survival. Based on this hypothesis, we will discuss and examine the drugs more frequently used for supportive therapy in neuro-oncologic patients. We assert, in fact, that the desire to offer neuro-oncologic patients better assistance guarantees not only adequate specialized input from the health operators involved, concerning the quality of life and the uniqueness of the 'person-patient', but also the ability to be able to listen to the patients, understand their choices and allow them to express their priorities.

Cerebellar atrophy and monoclonal gammopathy of undetermined significance: a possible correlation?

Central Nervous System involvement in Monoclonal gammopathies of undetermined significance has seldomly been reported and in all the cases a demyelinating disease was found. We report the case of a young man who had been suffering for five years of progressive cerebellar syndrome. MRI showed marked cerebellar vermis atrophy. An IgG lambda monoclonal gammopathy was revealed in the serum. Cerebrospinal fluid examination showed oligoclonal bands and elevated Link-Index. Serologic research for HBV, HCV, HIV, Lues, Rubella, Measles was negative, as also genetic analysis for SCA1, SCA2, SCA3, SCA7 and Friederich's ataxia. Nerve conduction studies were normal. Plasmatic vit.E was low, but treatment with high doses of tocopherol was ineffective. i.v. immunoglobulins and steroids obtained only transient clinical benefits. In conclusion, we hypothesize a pathogenetic role of the IgG in this cerebellar atrophy.

Spastic paraplegia, epilepsy, and mental retardation in several members of a family: a novel genetic disorder.

We report on a family in which an association between spastic paraplegia and epilepsy has been observed. This disorder is an autosomal dominant trait with incomplete penetrance and variable expressivity. The onset was limited to the first four decades of life; the symptoms were typically those of progressive weakness and spasticity of lower limbs. Epilepsy was present in members of three of the four generations on whom we have information. The concomitance of spastic paraplegia and epilepsy in several members of the same family is unlikely to be fortuitous and probably represents the pleiotropic effect of a single mutant gene.

Human growth hormone treatment in prepubertal children with achondroplasia.

We studied the effects of recombinant human growth hormone (GH) treatment in 6 prepubertal children with achondroplasia. The patients' age ranged from 2 11/12 to 8 5/12 years and the GH dose was of 0.1 IU/kg/day subcutaneously. Auxological assessments and bone age determinations were performed 6 months before, at the beginning, and after 6 and 12 months of therapy. The growth velocity increase during the whole year of treatment ranged from 1.1 to 2.6 cm/year in 3 patients while in the others no variation was detected. No side effects were observed during the trial apart from a slight advancement of bone age in two patients. MRI at the cervicomedullary junction and CT scan of the base of the skull did not show any variation of the dimensions of the foramen magnum at the end of the trial compared to baseline. Our study shows that r-hGH can safely increase short-term growth velocity in some but not all prepubertal children with achondroplasia. Our data confirm the individual variability in the response to the GH treatment.

Comparison of clinical-radiological and molecular findings in hypochondroplasia.

Hypochondroplasia is an autosomal dominant skeletal dysplasia characterized by disproportionate short stature. A mutation (N540K) in the fibroblast growth factor receptor 3 (FGFR3) gene was described in some patients with this condition. The aims of the study were to identify the frequency of the FGFR3 gene mutation, to define the salient clinical and radiological abnormalities of the affected subjects, and to verify the contribution of molecular findings to the clinical and radiological definition of hypochondroplasia. Based on the most common radiological criteria, we selected 18 patients with a phenotype compatible with hypochondroplasia. Height, sitting height, and cranial circumference were measured in all patients. Radiographs of the lumbar spine, left leg, pelvis, and left hand were also obtained. The presence of the N540K mutation was verified by restriction enzyme digestions. Half of our patients carried the N540K mutation. Although similar in phenotype to the patients without the mutation, they showed in addition relative macrocephaly. The association of the unchanged/narrow interpedicular distance with the fibula longer than the tibia was more common in patients with gene mutation. Although we did not find a firm correlation between genotype and phenotype, in our study the N540K mutation was most often associated with disproportionate short stature, macrocephaly, and with radiological findings of unchanged/narrow interpedicular distance and fibula longer than tibia.