Determinants of Cerebral Palsy in Pediatric Patients in Northern Ethiopia: A Hospital-Based Study

Introduction. Cerebral palsy is the most common neurologic disorder of childhood with lifelong implications in majority of patients. Knowledge of the determinants of cerebral palsy is important for accurate mobilization of resources in obstetric, perinatal, and infant care besides implementation of prevention systems. In Ethiopia, however, this knowledge gap exists as there are no published studies on determinants of cerebral palsy in the country. Objective. To assess the determinants of cerebral palsy in pediatric patients attending Ayder Comprehensive Specialized Referral Hospital between April 2019 and August 2019. Methods. An unmatched case-control study was conducted among 50 pediatric cerebral palsy patients and 100 controls, pediatric patients without cerebral palsy or other motor or central nervous system illnesses, attending Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia. The data were analyzed using SPSS version 27. Results. Significant factors were operative vaginal delivery (AOR: 9.49, 95% CI: 1.31–68.88), central nervous system infections (AOR: 0.02, 95% CI: 0–0.58), neonatal admissions (AOR: 0.13, 95% CI: 0.03–0.61), and unknown maternal education status (AOR: 18.64, 95% CI: 2.15–161.73). Conclusion. Operative vaginal delivery, central nervous system infections in infancy, neonatal hospital admissions, and unknown maternal education status were found to be significant determinants for cerebral palsy. This knowledge aids focused hospital and regional health bureau development and implementation of prevention strategies for cerebral palsy, besides improvement of obstetric and neonatal healthcare services, and provides baseline data to the scientific community for further research.

Limb Muscle Reinnervation with the Nerve-Muscle-Endplate Grafting Technique: An Anatomical Feasibility Study

Background. Peroneal nerve injuries results in tibialis anterior (TA) muscle paralysis. TA paralysis could cause “foot drop,” a disabling condition that can make walking difficult. As current treatment methods result in poor functional recovery, novel treatment approaches need to be studied. The aim of this study was to explore anatomical feasibility of limb reinnervation with our recently developed nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ). Methods. As the NMEG-NMZ technique involves in nerves and motor endplates (MEPs), the nerve supply patterns and locations of the MEP bands within the gastrocnemius (GM) and TA muscles of rats were investigated using Sihler’s stain and whole-mount acetylcholinesterase (AChE) staining, respectively. Five adult rats underwent TA nerve transaction. The denervated TA was reinnervated by transferring an NMEG pedicle from the ipsilateral lateral GM. At the end of a 3-month recovery period, maximal muscle force was measured to document functional recovery. Results. The results showed that the TA was innervated by the deep peroneal nerve. A single MEP band was located obliquely in the middle of the TA. The GM was composed of two neuromuscular compartments, lateral (GM-l) and medial (GM-m), each of which was innervated by a separate nerve branch derived from the tibial nerve and had a vertically positioned MEP band. The locations of MEP bands in the GM and TA muscles and nerve supply patterns demonstrated that an NMEG pedicle can be harvested from the GM-l and implanted into the NMZ within the TA muscle. The NMEG-NMZ pilot study showed that this technique resulted in optimal muscle force recovery. Conclusion. NMEG-NMZ surgery is feasible for limb reinnervation. Specifically, the denervated TA caused by peroneal nerve injuries can be reinnervated with a NMEG from the GM-l.

The SP/NK1R System-Mediated ROS Generation in GBM Cells through Inhibiting Glutaredoxin Protein

Altered redox balance is among the main contributing factors developing glioblastoma multiforme (GBM), a highly aggressive grade IV brain tumor. Neuropeptide substance P (SP) plays a key role in modifying the cellular redox environment by activating the neurokinin-1 receptor (NK1R). In this study, we aimed to investigate the redox-modulating properties of both SP and a commercially available NK1R antagonist, aprepitant in GBM cells. To detect the effect of aprepitant on the viability of U87 glioblastoma cells, resazurin assay was applied. The level of intracellular ROS was assessed using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) assay. The expression of glutaredoxin, a well-known redox-active protein, was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Concurrently, the activity of glutaredoxin was also analyzed by a commercial kit (ZellBio GmbH). We found that SP increased the intracellular levels of reactive oxygen species (ROS) in U87 GBM cells, and aprepitant remarkably decreased this effect. We also explored the effects of SP/NK1R signaling on the glutaredoxin system as a major cellular redox buffer in GBM cells. SP reduced both expression and enzymatic activity of glutaredoxin, and these effects were significantly decreased by aprepitant. In conclusion, our results suggest a possible involvement of SP/NK1R signaling in GBM pathogenesis through oxidative stress and offering new insight for the application of aprepitant as a redox-modulating strategy in GBM patients.

Investigation of the Possible Correlation between Idiopathic Parkinson’s Disease and Diabetes Mellitus in Egyptian Patients: A Pilot Study

Objectives. To study the diabetes-Parkinson's disease (PD) linkage. Methods. The investigators recorded the rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ) score for 60 diabetic patients: 30 patients were treated with metformin-inclusive sulfonylurea and 30 patients were treated with sulphonylurea(s) monotherapy and matched with 30 controls. We evaluated blood glucose kinetics during a 75 g oral glucose tolerance test for (22) nondiabetic parkinsonian patients and (10) controls. The motor complications scores were recorded for all parkinsonian patients using the relevant parts of the Unified Parkinson’s Disease Rating Scale (UPDRS) part IV. Results. Diabetics recorded higher scores of RBDSQ than controls ( p < 0.001 ), with no differences related to antidiabetic therapy. In nondiabetic PD patients, after oral glucose, blood glucose was significantly higher at T1 ( p < 0.001 ) than controls. Moreover, the total area under the time curve for blood glucose levels was significantly higher in PD compared to controls (281.22 ± 52.25 vs. 245.65 ± 48.63 mg.hr./dL; p = 0.013 ). Higher blood glucose levels were associated with motor abnormalities. Diabetic PD patients recorded higher scores of UPDRS ( p < 0.001 ). Conclusion. Diabetes mellitus and Parkinson’s disease are linked, which raises concerns about either of them, probably increasing the risk of the other. This trial is registered with NCT03685357.

Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates

Minimal myelination is proposed to be a contributing factor to the preferential nigral neuronal loss in Parkinson’s disease (PD). Similar to nigral dopaminergic neurons, sympathetic neurons innervating the heart have long, thin axons which are unmyelinated or minimally myelinated. Interestingly, cardiac sympathetic loss in PD is heterogeneous across the heart, yet the spatial relationship between myelination and neurodegeneration is unknown. Here, we report the mapping of myelin basic protein (MBP) expression across the left ventricle of normal rhesus macaques (n = 5) and animals intoxicated with systemic 6-OHDA (50 mg/kg iv) to model parkinsonian cardiac neurodegeneration (n = 10). A subset of 6-OHDA-treated rhesus received daily dosing of pioglitazone (5 mg/kg po; n = 5), a PPARγ agonist with neuroprotective properties. In normal animals, MBP-immunoreactivity (-ir) was identified surrounding approximately 14% of axonal fibers within nerve bundles of the left ventricle, with more myelinated nerve fibers at the base level of the left ventricle than the apex p < 0.014 . Greater MBP-ir at the base was related to a greater number of nerve bundles at that level relative to the apex p < 0.05 , as the percent of myelinated nerve fibers in bundles was not significantly different between levels of the heart. Cardiac sympathetic loss following 6-OHDA was associated with decreased MBP-ir in cardiac nerve bundles, with the percent decrease of MBP-ir greater in the apex (84.5%) than the base (52.0%). Interestingly, cardiac regions and levels with more MBP-ir in normal animals showed attenuated sympathetic loss relative to areas with less MBP-ir in 6-OHDA + placebo (r = −0.7, p < 0.014 ), but not in 6-OHDA + pioglitazone (r = −0.1) subjects. Our results demonstrate that myelination is present around a minority of left ventricle nerve bundle fibers, is heterogeneously distributed in the heart of rhesus macaques, and has a complex relationship with cardiac sympathetic neurodegeneration and neuroprotection.

Deficits in Working Memory and Theory of Mind May Underlie Difficulties in Social Perception of Children with ADHD

Children with attention deficit hyperactivity disorder (ADHD) are prone to peer rejection and disliking due to difficulties in social perception and interaction. To address social perception impairments in ADHD, we examined children with ADHD in a noisy biological motion (BM) direction discrimination paradigm in association with sociocognitive factors including emotion regulation, theory of mind (TOM), and working memory compared to healthy controls. Our results showed that children with ADHD were poorer in discriminating BM direction in noisy environments (F (1, 36) = 4.655, p = 0.038 ). Moreover, a significant correlation was found between working memory and TOM with BM discrimination in an ADHD group (r = 0.442, p = 0.01 , and r = 0.403, p = 0.05 , respectively). Our findings could suggest that social perception in noisy scenarios may be affected by memory and social cognitive abilities of children with ADHD.

The Role of ACE2 Receptors of the Olfactory System in Anosmia in COVID-19: An Overview

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). The latest data show that more than 211.7 million people were infected and more than 4.4 million deaths have been reported. The illness presents a wide range of symptoms, ranging from mild to severe. Mild symptoms include cough, fever, dyspnea, fatigue, myalgia and arthralgia, anosmia, and dysgeusia. Furthermore, this virus can affect the central nervous system (CNS) and present a range of mild to severe nervous symptoms, from headache and dysphoria to loss of consciousness, coma, paralysis, and acute cerebrovascular disease. The virus can enter nonneuronal cells of the olfactory epithelium and cause a complete loss of smell. Anosmia and hyposmia are commonly reported in clinics, and being asymptomatic or showing mild symptoms can be primary symptoms in early infected persons. Dysgeusia/hypogeusia is another symptom presented with anosmia/hyposmia. In this article, we reviewed the articles of anosmia and suggested a possible mechanism for this.

Factors Affecting Vagus Nerve Stimulation Outcomes in Epilepsy

Epilepsy as a common neurological disease is mostly managed effectively with antiepileptic medications. One-third of patients do not respond to medical treatments requiring alternative therapies. Vagus nerve stimulation (VNS) has been used in the last decades for the treatment of medically resistant epilepsy. Despite the extensive use of VNS in these patients, factors associated with clinical outcomes of VNS remain to be elucidated. In this study, we evaluated factors affecting VNS outcomes in epileptic patients to have a better understanding of patients who are better candidates for VNS therapy. Several databases including PubMed, Scopus, and Google Scholar were searched through June 2020 for relevant articles. The following factors were assessed in this review: previous surgical history, age at implantation and gender, types of epilepsy, duration of epilepsy, age at epilepsy onset, frequency of attacks, antiepileptic drugs, VNS parameters, EEG findings, MRI findings, and biomarkers. Literature data show that nonresponder rates range between 25% and 65%. Given the complexity and diversity of factors associated with response to VNS, more clinical studies are needed to establish better paradigm for selection of patients for VNS therapy.

Comparable Efficacy and Safety of Teriflunomide versus Dimethyl Fumarate for the Treatment of Relapsing-Remitting Multiple Sclerosis

Background. The aim of this observational study is to investigate the efficacy and safety of two approved oral disease-modifying therapies (DMTs) in patients with remitting-relapsing multiple sclerosis (RRMS): dimethyl fumarate (DMF) vs. teriflunomide (TRF). Methods. A total of 159 RRMS patients (82 on TRF and 77 on DMF) were included. The expanded disability status scale (EDSS), confirmed disability improvement (CDI), confirmed disability progression (CDP), and annualized relapse rate (ARR) were evaluated for the two-year period prior to enrollment in our study. The drug-associated adverse effects (AEs) were recorded. We conducted propensity matching score to compare the efficacy between TRF and DMF. Results. After matching for the confounders, TRF- and DMF-treated groups were not different in terms of EDSS ( P value = 0.54), CDI ( P value = 0.80), CDP ( P value = 0.39), and ARR ( P value >0.05). TRF discontinuation occurred in 2 patients (2.43%) due to mediastinitis and liver dysfunction, while a patient (1.29%) discontinued DMF due to depression. Incidence rate of AEs in the TRF-treated group was 81.4%: hair thinning (hair loss) (62.9%), nail loss (20.9%), and elevated aminotransferase (14.8%) were the most common AEs; in DMF-treated patients, AEs were 88.2% with predominance of flushing (73.2%), pruritus (16.9%), and abdominal pain (16.9%). Conclusion. Based on our findings, DMF is as efficacious and safe as TRF for the treatment of RRMS in our Iranian study population. Multicentric studies need to corroborate these findings in other populations.

An Insight into the Current Understanding of Status Epilepticus: From Concept to Management

Status epilepticus (SE), a subset of epilepsy, represents a debilitating neurological disorder often associated with alarming mortality and morbidity numbers. Even though SE is one of the extensively researched topics with conspicuous data available in the literature, a scientific gap exists in understanding the heterogeneous facets of the disorder like occurrence, definition, classification, causes, molecular mechanisms, etc., thereby providing a defined management program. Cognizance of this heterogeneity and scientific limitation with its subsequent correlation to the recent advancements in medical and scientific domains would serve not only in bridging the gap but also in developing holistic and prompt management programs. Keeping this as an objective, an extensive literature survey was performed during this study, and key findings have been shared. The present study provides a semantic and perspective synopsis toward acknowledging the diversified nature of SE and its variants with respect to their definition, classification, etiology, diagnosis, and management.