A cross-sectional and longitudinal study of changes in complex networks related to brain function in temporal lobe epilepsy patients treated with levetiracetam intervention therapy.

The aim of this study was to investigate the thyroid functions in children receiving levetiracetam or valproate monotherapy. We retrospectively reviewed the records of children with controlled epilepsy receiving valproic acid (VPA group) or levetiracetam monotherapy (LEV group) for at least 6 months. Free thyroxine 4 levels (fT4) and thyroid stimulating hormone (TSH) levels were compared between VPA group, LEV group, and age- and gender-matched healthy children (control group). A total of 190 children were included in the study: 63 were in the VPA, 60 in the LEV, and 67 in the control group. Although there was no significant difference regarding average fT4 levels, higher TSH levels were found in the VPA group when compared with the LEV and control groups (p < 0.001 and p < 0.001, respectively). There was no significant difference in terms of fT4 and TSH values in the LEV group when compared with the control group (p = 0.56 and p = 0.61, respectively). Subclinical hypothyroidism (defined as a TSH level above 5 uIU/mL with a normal fT4 level was detected in 16% of patients in the VPA group, none in the LEV and control groups. Our study found that VPA therapy is associated with an increased risk of subclinical hypothyroidism while LEV had no effect on thyroid function tests.

ObjectiveThe objective of this study was to evaluate the effect of toluidine blue-mediated photodynamic therapy on experimental bacterial keratitis in rabbits.MethodsBacterial keratitis was induced in rabbits by the injection of 200 μl Staphylococcus aureus (S. aureus) solution into the anterior stroma of the right cornea. Rabbits were randomly divided into four groups: toluidine blue O and red light (TBOR), levofloxacin eye drops (LEV), the combination of TBOR and LEV (TBOR + LEV), and a control group. Clinical manifestations, histopathology, and transmission electron microscopy were analyzed at various time points.ResultsConjunctival injection and surface area of the corneal ulcer in the TBOR group and the TBOR + LEV group showed significant improvement from baseline after 7 days of treatment. Compared to baseline, the depth of corneal infiltration was decreased at day 14 in the TBOR and TBOR + LEV groups. Microscopic analysis of the TBOR and TBOR + LEV groups showed that the structure of each layer was intact, and there were no inflammatory cells in the corneal stroma. Additionally, IL-1β and TNF-α were highly expressed in the LEV and control groups but were lower in the TBOR and TBOR + LEV groups. Under transmission electron microscopy, the corneas in the TBOR and TBOR + LEV groups were intact, whereas in the LEV and control groups, double-walled structures corresponding to S. aureus were found in the superficial stromal layer.ConclusionsTBOR demonstrated in vivo antibacterial efficacy against S. aureus.Translational RelevanceThis study found in vivo antibacterial efficacy of toluidine blue-mediated photodynamic therapy on rabbit experimental bacterial keratitis, thus providing an additional new option for clinical treatment of bacterial keratitis.

Irritability and its relationship with psychosocial symptoms and quality of life in adolescents with epilepsy receiving levetiracetam therapy: A case-control study

Postoperative pain is less intense after laparoscopic surgery than after open surgery. However, patients may gain additional benefit from a preincisional local infiltration of anesthetic. The aim of this study was to compare the analgesic efficacy of two local anesthetics, ropivacaine and levobupivacaine, for tissue infiltration as a means of improving postoperative pain control after laparoscopic cholecystectomy. Using a randomized, double-blind study design, 57 American Society of Anesthesiologists (ASA) I and II patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive local infiltration with 0.9% saline solution (Placebo group, n = 18), ropivacaine 1% (Rop group, n = 20), or levobupivacaine 0.5% (Lev group, n = 19). The local anesthetic was administered, prior to trocar placement, using the same technique and delivering the same volume (20 ml) for all three groups. The anesthetic technique was standardized for all groups. Postoperative pain was rated at 2 h, 4 h, and 24 h postoperatively by visual analogue scale (VAS) score. Cumulative analgesic consumption and adverse effects were also recorded. Data were analyzed by analysis of variance (ANOVA), followed by a post hoc test. The Lev and Rop groups did not differ significantly in their VAS scores at 2 h postoperatively, but the Lev group experienced significantly ( p < 0.001) less pain than the Placebo and Rop groups at 4 h and 24 h postoperatively. The Rop group registered significantly lower VAS scores ( p < 0.001) than the Placebo group at 4 h postoperatively. Additionally, the consumption of analgesics was significantly lower in the Lev group than in the Rop ( p < 0.01) and Placebo ( p < 0.001) groups, and patients in the Rop group consumed significantly less analgesics ( p < 0.001) than the to patients in the Placebo group. Local tissue infiltration with levobupivacaine is more effective than ropivacaine in reducing the postoperative pain associated with laparoscopic cholecystectomy.

We examined possible neuroprotective and prophylactic effects of chronic pre-treatment with levetiracetam (Lev), topiramate (Tpm), and lacosamide (Lcm) on the pentylenetetrazol (PTZ)-induced status epilepticus (SE) in rat pups. Forty-six rats were divided into four groups; all of them were on postnatal day (PD) 21 i.p. injected with 60 mg/kg PTZ. Rat pups of three experimental groups were pre-treated during 14 days (PD7–PD21) with Tpm, Lcm, or Lev via gavage in doses of 60, 50, and 150 mg/kg per day, respectively; animals of the PTZ group were treated with 0.2 ml saline per day. Animals of the latter group demonstrated intense behavioral changes of a stage 3 of the Racine scale or higher, while no significant behavioral alterations were observed in all pre-treated groups. Protein carbonyl and TBARS levels were markedly elevated in the PTZ group, while these indices were significantly smaller in the Tpm and Lev groups. Immunohistochemical analysis demonstrated an increased apoptosis level in hippocampal pyramidal neurons in the Lev group with respect to the PTZ group. In the open field test, the total distance moved and duration of stay in the outer squares were significantly greater in the PTZ group than in the Lcm and Lev groups. Thus, Tpm, Lcm, and Lev treatment provided clear prophylactic effects on the PTZ-induced SE development; such treatment decreased the intensity of oxidative stress and protected from changes in locomotor activity and anxietyrelated behavior in immature organisms. However, some pro-apoptotic action of Lev on the developing hippocampus needs to be noted and investigated in more detail.

Pretreatment with intravenous levetiracetam in the rhesus monkey Coriaria lactone-induced status epilepticus model

Modulation of cardiac renin-angiotensin system, redox status and inflammatory profile by different volumes of aerobic exercise training in obese rats

Comparison of intra and postoperative analgesia efficacy of intraperitoneal levobupivacaine alone or in combination with dexmedetomidine in cats undergoing ovariohysterectomy; a randomized, prospective, blinded, clinical trial

Sheep pox infection poses a significant socio-economic threat to sheep production worldwide. Vaccination is the most effective preventive measure against this disease. This study examines the immunomodulatory effects of various immunostimulants on the immune response of Barki ewes to the live-attenuated sheep pox Vaccine. Sixty Barki ewes were vaccinated with the live-attenuated sheep pox vaccine and divided into four groups: Pox (vaccine only), BCG (vaccine + 0.1 ml BCG), E+Se (vaccine + 0.5 ml/10 kg Vitamin E + Selenium) and Lev (vaccine + 1 ml Levamisole 10%/50 kg). Blood samples were collected to assess humoral immunity (NI), innate immunity, and clinicopathological parameters. The E+Se group showed the best NI, minimal innate immunological alterations, normal hemogram, liver, and kidney function tests, and improved total protein, globulin levels, and neutrophil phagocytic index. The Lev group had NI values close to the Pox group, while the BCG group had lower NI than the Pox group. Innate immunological alterations and haemato-biochemical changes were more pronounced in the Lev and BCG groups compared to the Pox group and in the BCG group compared to the Lev group. Conclusion: The E+Se injection before the live-attenuated sheep pox vaccine significantly enhanced the ewes' humoral immune response and reduced vaccination side effects.

To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add-on therapy in patients with refractory partial seizures. In this European multicenter, double-blind, randomized, placebo-controlled trial, LEV (500 or 1,000 mg twice daily) was compared with placebo as add-on therapy in 324 patients with uncontrolled simple or complex partial seizures, or both, with or without secondary generalization. After enrollment, three parallel groups were assessed during a baseline period of 8 or 12 weeks, followed by a 4-week titration interval and a 12-week evaluation period. LEV significantly decreased partial seizure frequency compared with placebo. A reduction in seizure frequency of > or =50% occurred in 22.8% of patients in the 1,000-mg group and 31.6% of patients in the 2,000-mg group, compared with 10.4% of patients in the placebo group. Administration of LEV did not affect plasma concentrations of concomitant antiepileptic drugs or alter vital signs or laboratory parameters. No significant difference in the incidence of adverse events was observed between treatment groups (70.8% for the 1,000-mg group and 75.5% for the 2,000-mg group), or between the LEV and placebo groups (73.2% for placebo group). The most commonly reported adverse effects in the LEV group were asthenia, headache, and somnolence. The antiepileptic efficacy and tolerability of LEV (1,000 mg/d and 2,000 mg/d, administered in two divided doses) as add-on therapy was established in patients with refractory partial seizures in this clinical study.

Impaired brain network architecture in newly diagnosed Parkinson's disease based on graph theoretical analysis.

Neuroimaging studies have revealed that shift work disorder (SWD) affected the functional connectivity in specific brain regions and networks. However, topological disruptions in the structural connectivity of the white matter (WM) networks associated with attention function remain poorly understood. In the current study, we recruited 33 patients with SWD and 29 matched healthy subjects. The attention network test (ANT) was employed to investigate the efficiency of alerting, orienting, and executive control networks. The diffusion tensor imaging (DTI) tractography was used to construct the WM structural networks. The graph theory analysis was applied to detect the alterations of topological properties of structural networks. Our results showed lower alerting effect and higher executive effect for patients with SWD. Using the link-based analysis, 15 altered connectivity matrices (lower fiber numbers) were found between the two groups. Meanwhile, the graph theoretical analysis showed that the global efficiency and characteristic path length within SWD patients declined in contrast with the healthy controls. Furthermore, a significantly negative correlation was found between the executive effect and global network efficiency. Our findings provide the new insights into the fundamental architecture of interregional structural connectivity underlying attention deficits in SWD, which may be a potential biomarker for SWD.

ObjectiveThe study aimed to find the difference in functional network topology on interictal electroencephalographic (EEG) between patients with drug-resistant epilepsy (DRE) and healthy people.MethodsWe retrospectively analyzed the medical records as well as EEG data of ten patients with DRE and recruited five sex-age-matched healthy controls (HC group). Each participant remained awake while undergoing video-electroencephalography (vEEG) monitoring. After excluding data that contained abnormal discharges, we screened EEG segments that were free of artifacts and put them together into 20-min segments. The screened data was bandpass filtered to different frequency bands (delta, theta, alpha, beta, and gamma). The weighted phase lag index (wPLI) and the network properties were calculated to evaluate changes in the topology of the functional network. Finally, the results were statistically analyzed, and the false discovery rate (FDR) was used to correct for differences after multiple comparisons.ResultsIn the full frequency band (0.5–45 Hz), the functional connectivity in the DRE group during the interictal period was significantly lower than that in the HC group (p < 0.05). Compared to the HC group, in the full frequency band, the DRE group exhibited significantly decreased clustering coefficient (CC), node degree (D), and global efficiency (GE), while the characteristic path length (CPL) significantly increased (p < 0.05). In the sub-frequency bands, the functional connectivity of the DRE group was significantly lower than that of the HC group in the delta band but higher in the alpha, beta, and gamma bands (p < 0.05). The statistical results of network properties revealed that in the delta band, the DRE group had significantly decreased values for D, CC, and GE, but in the alpha, beta, and gamma bands, these values were significantly increased (p < 0.05). Additionally, the CPL of the DRE group significantly increased in the delta and theta bands but significantly decreased in the alpha, beta, and gamma bands (p < 0.05).ConclusionThe topology structure of the functional network in DRE patients was significantly changed compared with healthy people, which was reflected in different frequency bands. It provided a theoretical basis for understanding the pathological network alterations of DRE.

BACKGROUND Patients with brain tumors often experience decline in neurocognitive functioning (NCF) following surgical tumor resection. Connectomic studies have begun to uncover how abnormalities to underlying cerebral networks contribute to NCF deficits; however, few studies have investigated relationships between pre- to postoperative changes in structural connectomics and NCF. METHODS Fifteen right-handed adults with left perisylvian tumors underwent MRI of the brain with diffusion tensor imaging (DTI) and neuropsychological assessment before and after awake tumor resection. Graph theoretical analysis was applied to DTI-derived connectivity matrices to calculate structural network properties. Structural network properties and NCF measures were compared across the pre- to postoperative periods with matched pairs Wilcoxon signed-rank tests. Associations between pre- to postoperative change in network properties and change in NCF were determined with Spearman rank-order correlations (ρ). RESULTS Nearly 90% of the sample showed postoperative decline on 1 or more NCF measures. Significant postoperative NCF decline was found across measures of verbal memory, processing speed, executive functioning, receptive language, and the Clinical Trial Battery Composite (CTB COMP) index. Regarding connectomic properties, significant postoperative changes were observed in global and local efficiency, characteristic path length, clustering coefficient, betweenness centrality, and assortativity, with medium effect sizes. Significant associations (ρ = .59 to .62, all p &amp;lt; .05) were observed between changes in aspects of NCF and connectomic properties. CONCLUSIONS Decline in NCF was common following resection and some postoperative outcomes were associated with changes in structural connectomic properties following surgery.

Cognitive impairment after traumatic brain injury (TBI) is persistent and disabling. Assessing cognitive function in a reliable and valid manner, using measures that are sensitive to the integrity of underlying neural substrates, is crucial in clinical research. The Attention Network Test (ANT) is one such assessment measure that has demonstrated associations with neural regions involved in attention; however, clinical utility of the ANT is limited because its relationship with neuropsychological measures of cognitive function (i.e., its construct validity) has not yet been established in TBI. We evaluated the association between the ANT and 1) a neuropsychological battery assessing executive function and memory and 2) global function assessed by the Glasgow Outcome Scale-Extended (GOSE). Forty-eight adults with complicated mild-severe TBI were evaluated ∼5 months post-injury. Using principal component analysis and multi-variate linear regression adjusted for age, gender, education, and cause of injury, we found that ANT reaction time and executive network scores predicted a principal component assessing processing speed and executive function. Conversely, the ANT did not predict a principal component assessing memory. The ANT was weakly associated with the GOSE. Among persons with TBI during the post-acute phase of recovery, the ANT has good construct validity as evidenced by its associations with neuropsychological measures of processing speed and executive function, but not memory. Given that ANT networks are known to relate to specific neuroanatomical regions, the ANT may be a useful outcome measure for evaluating novel therapeutics targeting attention and executive functions after TBI.