ILAE Neuroimaging Task Force Highlight: harnessing optimized imaging protocols for drug-resistant childhood epilepsy.

The ILAE Neuroimaging Task Force aims to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Previous quantitative MRI studies have established important imaging markers of epilepsy-related pathology, including features sensitive to hippocampal cell loss and reactive astrogliosis. Here, we review the case of a female with pediatric drug-resistant epilepsy. Throughout her course of treatment, she had seven MRI investigations at several centers; the first three did not follow optimized epilepsy imaging protocols whereas the remaining four adhered to HARNESS-MRI protocols ( har monized n euroimaging of e pilepsy s tructural s equences). Visual inspection of a set of HARNESS-MR images revealed conspicuous left hippocampal hyperintensity which may have been initially overlooked on non-optimized MR images. Quantitative analysis of these multimodal imaging data along hippocampal subfields provided clear evidence of hippocampal sclerosis, with increased atrophy, increased mean diffusivity, increased T2-FLAIR signal, and lower qT1 values observed in the anterior portions of the left, compared to the right hippocampus. The patient underwent a left anterior temporal lobectomy with amygdalohippocampectomy at age 16 years. Histopathology of the resected specimen also confirmed hippocampal sclerosis with widespread gliosis and focal neuronal loss in the hippocampal subfields overlapping with regions of multimodal quantitative alterations. The patient remains seizure-free one year after surgery. Collectively, this case highlights the need for optimized data acquisition protocols early in the treatment of epilepsy and supports quantitative analysis of MRI contrasts to enhance personalized diagnosis and prognosis of drug-resistant patients with epilepsy.

Impact of Serum Troponin I Levels on short-term outcomes following an acute ischemic stroke

BACKGROUND@#There is a complex relationship between coronary artery disease and stroke. Troponin I has been investigated for its potential as a prognostic biomarker in determining outcome and mortality after an acute cerebrovascular insult such as an ischemia. Several studies have been done mostly in Western countries leaving very little data for patients of Asian/Southeast Asian descent. Its implications in the prognosis and management of acute ischemic stroke may guide clinicians in rendering the most suitable care for their patients. @*OBJECTIVE@#This study aims to identify the impact of serum troponin I levels on short-term functional outcome after an acute ischemic cerebrovascular event. It also intends to evaluate the role of cardiac troponin I in identifying the prognosis and in-hospital mortality among patients with acute ischemic stroke.@*METHODS@#A prospective cohort study was done from August 2019 to February 2020 including 65 adult acute ischemic stroke patients (35 males and 30 females) coming to consult within 48 hours from ictus. Baseline electrocardiogram was done. Patients without evidence of an acute ACS and other cardiac diseases were included. Blood samples for determination of serum troponin I were collected. Patients were monitored for development of complications and incidence of in-hospital mortality. Sixty days from onset, short-term functional outcome was assessed by determining change in NIHSS score. Modified Rankin Scale (mRS) was used to assess degree of disability on follow-up. @*RESULTS@#Out of 65 patients initially enrolled, 23 (35.38%) had abnormally elevated troponin I. Patients with history of previous stroke and higher NIHSS scores on admission tend to have elevated troponin I. Patients with elevated troponin I had worse short-term functional outcome and were dependent in performing daily activities. This study did not demonstrate a predictive value of elevated troponin I for in-hospital mortality. @*CONCLUSION@#In patients with acute ischemic stroke, elevation of serum TnI has been observed even in the absence of a definite clinical acute coronary syndrome. Presence of previous stroke and more severe neurologic deficits has been shown to be related to elevations in TnI. This elevation in TnI, in turn, is associated with poor short-term outcome limiting patients’ functionality and independence. Managing these patients necessitate aggressive but judicious use of different diagnostic and treatment modalities to prevent adverse coronary events. These events are likely to be prevented when early recognition and proper management has been provided.

Recovering from the Ebola crisis: 'Social Reconnection Groups' in a rural Liberian community.

In 2014/2015, International Medical Corps (IMC) operated two Ebola Treatment Units (ETUs) in Liberia and three in Sierra Leone when the Ebola virus disease epidemic killed over 11,000 people across Liberia, Sierra Leone and Guinea. As Ebola cases declined in Liberia, IMC Psychosocial teams transitioned to working in communities highly affected by the epidemic. This article describes IMC's experience with developing and implementing a community-based mental health and psychosocial group intervention in a rural, severely affected Liberian town - Mawah - where 46 out of approximately 800 community members were infected, 39 of whom died. In this paper, we present how the group intervention, named 'Social Reconnection Groups', was developed and implemented. We then discuss intervention strengths, challenges, key lessons learnt and recommendations for how Social Reconnection Groups can be adapted for use in similar settings.

Stroke thrombolysis in the Philippines

Background & Objective: Currentlythere is limitedintervention for acute ischemic stroke. Recombinant tissue plasminogen activator (rTPA) has been approved for immediate recanalization after a steno-occlusive lesion of cerebral vessels. rTPA has shown its efficacy and safety from several clinical trials. The present study reports our experience with intravenous rTPA from several centers in the Philippines.Method:This is a retrospective cohort study consisting of 157 patients who qualified to receive rTPA following the NINDS trial inclusion and exclusion criteria. The primary outcome is in-hospital and 3-months mortality. Other outcome measures were determined: intracranial hemorrhage secondary to hemorrhagic conversion and functional outcome as measured by modified Rankin Scale. Additionally, standard dose (0.9mg/kg) was compared to low dose (0.6mg/kg) of rTPA in terms of mortality, intracranial bleeding and functional outcome.Results:The in-hospital mortality was seen in 23 (14.6%) and total death within 3 months was 18.3%. Independent patient (mRS 0-2) was seen in 69 (51.1%) at discharge and 95 (73.1%) at 3 months. Intracranial bleeding due to asymptomatic hemorrhagic transformation occurred in 39 (24.8%) and symptomatic hemorrhagic transformation was seen in 19 (12.1%).Conclusion: Comparing our results with SITS-MOST and Cochrane collaborations, our data showed that we have more independent patients however death and intracranial bleeding was noted to be high in our cohort of patients. Additionally, the study showed more independent patients in the low dose group.

Spatial relationship between fast and slow components of ictal activities and interictal epileptiform discharges in epileptic spasms.

OBJECTIVE: We analyzed the spatial distribution and concordance of fast (>10Hz) and slow (<5Hz) electroencephalogram (EEG) components of ictal activities and interictal epileptiform discharges (IIED) recorded by intracranial video EEG (IVEEG) in children with epileptic spasms (ES). METHODS: We studied eight children with ES, who underwent IVEEG before resective surgery for epilepsy. We quantified the root-mean-square (RMS) amplitude of the fast and slow components of ictal activities during ES and IIED. We compared the concordance between the spatial distributions of the fast and slow components of ES and IIED. RESULTS: There was a larger concordance between the spatial distributions of the fast and slow components in IIED than in ES (p=0.0206 and 0.0401). CONCLUSIONS: The spatial concordance between the fast and slow EEG components was significantly different between ES and IIED. SIGNIFICANCE: The mechanisms underlying the generation of slow EEG components may differ between ES and IIED. The slow EEG components of ES might indicate an extensive epileptic network involving remote symptomatic zones for ES in either the cortical or subcortical areas. The high spatial concordance between the fast and slow components of IIED suggests the involvement of a local inhibitory process within the epileptic cortex.

Curtailing the hydroxylaminobarbituric acid-hydantoin rearrangement to favor HNO generation.

Due to its inherent reactivity, HNO must be generated in situ through the use of donor compounds. One of the primary strategies for the development of new HNO donors has been modifying hydroxylamines with good leaving groups. A recent example of this strategy is the (hydroxylamino)barbituric acid (HABA) class of HNO donors. In this case, however, an undesired intramolecular rearrangement pathway to the corresponding hydantoin derivative competes with HNO formation, particularly in the absence of chemical traps for HNO. This competitive non-HNO-producing pathway has restricted the development of the HABA class to examples with fast HNO release profiles at physiological pH and temperature (t(1/2) < 1 min). Herein, the factors that favor the rearrangement pathway have been examined and two independent strategies that protect against rearrangement to favor HNO generation have been developed. The timecourse and stoichiometry for the in vitro conversion of these compounds to HNO (trapped as a phosphine aza-ylide) and the corresponding barbituric acid (BA) byproduct have been determined by (1)H NMR spectroscopy under physiologically relevant conditions. These results confirm the successful extension of the HABA class of pure HNO donors with half-lives at pH 7.4, 37 °C ranging from 19 to 107 min.

"Catch-and-release" of HNO with pyrazolones.

A new and versatile class of HNO donors, the (hydroxylamino)pyrazolone (HAPY) series of HNO donors utilizing pyrazolone (PY) leaving groups, is described. HNO, the smallest N-based aldehyde equivalent, is used as a reagent along with a variety of PY compounds to synthesize the desired HAPY donors in what can be considered an N-selective HNO-aldol reaction in up to quantitative yields. The bimolecular rate constant of HNO with PY in pH 7.4 phosphate buffer at 37 °C can reach 8 × 10(5) M(-1) s(-1). In (1)H NMR experiments, the HAPY compounds generate HNO quantitatively (trapped as a phosphine aza-ylide) with half-lives spanning 3 orders of magnitude (minutes to days) under physiologically relevant conditions. B3LYP/6-31G* calculations confirm the energetically favorable reactions between HNO and the PY enol and enolate, whereas HNO release is expected to occur through the oxyanion (OHN-PY) of each HAPY compound. HNO has been shown to provide functional support to failing hearts.

Synthesis and reactivity of new aminophenolate complexes of nickel.

New well-defined, paramagnetic nickel complexes have been prepared and characterized by X-ray crystallography. The complexes were found to be active for the cross-coupling of alkyl electrophiles (especially ethyl 2-bromobutyrate) with alkyl Grignard reagents. The ligand architecture in these new complexes could potentially be rendered chiral, opening up future possibilities for performing asymmetric cross-coupling reactions.

Screening of some Kenyan medicinal plants for antibacterial activity.

Eleven medicinal plants used by traditional healers in Machakos and Kitui District were screened, namely: Ajuga remota Benth, Aloe secundiflora Engl, Amaranthus hybridus L, Cassia didymobotrya Fes, Croton macrostachyus Del, Entada leptostachya Harms, Erythrina abyssinica DC, Harrisonia abyssinica Oliv, Schkuhria pinnata O. Ktze, Terminalia kilimandscharica Engl and Ziziphus abyssinica Hochst for potential antibacterial activity against four medically important bacterial strains, namely: Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, Micrococcus lutea ATCC 9341 and Pseudomonas aeruginosa ATCC 27853. The antibacterial activity of methanol extracts was determined as the minimum inhibitory concentration (MIC). The plant extracts were more active against Gram-positive (G+) than Gram-negative (G-) bacteria. The positive controls were streptomycin and benzylpenicillin for G- and G+ bacteria, respectively, both had a significant MIC at <1 mg/mL. The most susceptible bacteria were B. cereus, followed by M. lutea, while the most resistant bacteria were Ps. aeruginosa, followed by E. coli. The present study supports the use of these plants by the herbalists in the management of bacterial ailments. H. abyssinica and T. kilimandscharica showed the best antibacterial activity; hence these plants can be further subjected to phytochemical and pharmacological evaluation.

Ethnopharmacological survey of Samburu district, Kenya.

BACKGROUND: Ethnobotanical pharmacopoeia is confidently used in disease intervention and there is need for documentation and preservation of traditional medical knowledge to bolster the discovery of novel drugs. The objective of the present study was to document the indigenous medicinal plant utilization, management and their extinction threats in Samburu District, Kenya. METHODS: Field research was conducted in six divisions of Samburu District in Kenya. We randomly sampled 100 consented interviewees stratified by age, gender, occupation and level of education. We collected plant use data through semi-structured questionnaires; transect walks, oral interviews and focus groups discussions. Voucher specimens of all cited botanic species were collected and deposited at University of Nairobi's botany herbarium. RESULTS: Data on plant use from the informants yielded 990 citations on 56 medicinal plant species, which are used to treat 54 different animal and human diseases including; malaria, digestive disorders, respiratory syndromes and ectoparasites. CONCLUSION: The ethnomedicinal use of plant species was documented in the study area for treatment of both human and veterinary diseases. The local population has high ethnobotanical knowledge and has adopted sound management conservation practices. The major threatening factors reported were anthropogenic and natural. Ethnomedical documentation and sustainable plant utilization can support drug discovery efforts in developing countries.

Involvement of the alpha3 subunit in central nicotinic binding populations.

The alpha3 subunit gene was one of the first neuronal nicotinic acetylcholine receptor (nAChR) subunits to be cloned (Boulter et al., 1986), but direct evidence of alpha3 subunit contributions to mammalian central nAChR populations has not been presented. The studies reported here used mice engineered to contain a null mutation in the alpha3 nAChR subunit gene (Xu et al., 1999) to examine the involvement of the alpha3 subunit in central nAChR populations. Heterologously expressed alpha3beta2 and alpha3beta4 nAChRs are pharmacologically similar to native [125I]alpha-conotoxin MII (alpha-CtxMII)-binding and 3-(2(S)-azetidinylmethoxy)pyridine dihydrochloride (A85380)-resistant [125I]epibatidine-binding nAChR subtypes, respectively. The hypothesis that both native sites are alpha3-subtype nAChRs was tested using quantitative autoradiography in alpha3-null mutant mice. Somewhat surprisingly, deletion of the alpha3 nAChR subunit gene did not affect expression of the great majority of [125I]alpha-CtxMII-binding sites, indicating that they do not correspond to heterologously expressed alpha3beta2 nAChRs. The only exception to this was observed in the habenulointerpeduncular tract, where alpha3-dependent [125I]alpha-CtxMII binding was observed. This finding may suggest the presence of an additional, minor nicotinic population in this pathway. In contrast, most -resistant [125I]epibatidine-binding nAChRs were dependent on alpha3 gene expression, suggesting that they do indeed correspond to an alpha3 nAChR subtype. However, widespread but lower levels of alpha3-independent -resistant [125I]epibatidine binding were also seen. Again, this may indicate the existence of an additional, minor population of non-alpha3 -resistant sites.