Focal Seizures in a Child Receiving Terbutaline Sulfate: A Case Report.

Terbutaline sulfate is a beta-adrenergic receptor agonist. More specific for B2 receptors, it is used as a bronchodilator in asthma. Its known side effects can include dizziness, tremors, and tachycardia. However, seizures are not among the commonly reported side effects. This is the case of a five-month-old girl who presented with focal seizures after the intake of terbutaline sulfate syrup. Other causes of the seizures were excluded through history and investigations, including an EEG and electrolyte panel. The seizures stopped on cessation of the terbutaline sulfate with no recurrence, leading us to believe that the focal seizures were an adverse effect of the terbutaline sulfate. A high index of suspicion for drug-related adverse effects should therefore be kept for a child with new onset focal seizures.

Persistent Shoulder Pain After Anterior Cervical Discectomy and Fusion (ACDF): Another Dual Pathology.

Purpose It is often difficult for the clinician to isolate the etiology of pain occurring either in the neck or shoulder because of the reason that neck pain can refer to the shoulder and vice versa. Concordance research has found that around one in 10 patients who were referred for cervical radiculopathy had comorbid shoulder pathology. The goal of this research is to analyze and correlate risk factors for persistent shoulder pain (non-dermatomal) following cervical spine surgery. Methods This was a single-center, retrospective study. The medical records of patients admitted for anterior cervical discectomy and fusion (ACDF) were reviewed from August 2018 to Feb 2021. Patients of both sexes and age more than 18 years who underwent ACDF (single/multiple levels) were included and the medical record was checked for whether they had persistent shoulder pain following ACDF. The proportion of patients undergoing shoulder surgery for associated rotator cuff tears and subacromial impingement were recorded. Results Seventy patients presenting with cervical prolapsed intervertebral disc (PID) were studied. A majority of our patients were females (n=48, 68.6%) and males (n=22, 31.4%) with an M:F ratio of 1:2 and the majority of patients were between the ages of 40 to 60 years (n=34, 48.6%). After surgical intervention (ACDF), 48 patients (68.6%) noted the cessation of shoulder symptoms (pain, weakness, and numbness) during their last visit. Rotator cuff tear (supraspinatus mainly) was the predominant finding in MRI in those who didn't improve after ACDF (n=18, 25.7%, p-value: 0.001). Twenty patients (28.6%) underwent acromioplasty and rotator cuff tendon repair and four patients responded well to subacromial injection. The C6-7 level was most commonly affected (n=48, 68.6%) followed by C5-6 level (n=19, 27.1%). No significant association was found between cervical levels with shoulder pathologies (p-0.171), though a significant association between a visual analog scale (VAS) score >7 after surgery with shoulder pathologies (p-0.001) was found. The C6-7 level was commonly affected in females (p=0.038) but no significant association between gender and shoulder pathologies was found (p=0.332). Conclusion Dual pathologies in patients with cervical PID are very common. It needs careful attention by doing thorough clinical examination and correlating patient symptoms with radiological investigations. A patient who presents with persistent shoulder pain after cervical spine surgery had a higher chance of having concurrent shoulder pathology, and they should be properly investigated and managed to alleviate the suffering of the patient.

Treatment of Drug-resistant Pneumococcal Meningitis.

The approach to therapy in patients with pneumococcal meningitis has changed considerably over the past 20 years. Given the emergence of pneumococcal strains that are intermediately susceptible or highly resistant to penicillin, penicillin is not recommended as empiric therapy for presumed pneumococcal meningitis; the combination of vancomycin and a third-generation cephalosporin (either cefotaxime or ceftriaxone) should be used, pending isolation of the organism and in vitro susceptibility testing. For patients with pneumococcal meningitis caused by highly penicillin- or cephalosporin-resistant strains, the addition of rifampin can be considered if the organism is susceptible in vitro, the expected clinical or bacteriologic response is delayed, or the pneumococcal isolate has a cefotaxime or ceftriaxone minimal inhibitory concentration greater than 4 µg/mL. Meropenem is not a good option for monotherapy of highly penicillin- or cephalosporin-resistant strains, but use of a fluoroquinolone with in vitro activity against Streptococcus pneumoniae (specifically moxifloxacin) is an option in patients failing standard therapy; if used, however, it should be combined with a third-generation cephalosporin or vancomycin. Newer glycopeptides, daptomycin, and linezolid require further study to determine their efficacy in patients with pneumococcal meningitis.

Fetzima (levomilnacipran), a drug for major depressive disorder as a dual inhibitor for human serotonin transporters and beta-site amyloid precursor protein cleaving enzyme-1.

Pharmacological management of Major Depressive Disorder includes the use of serotonin reuptake inhibitors which targets serotonin transporters (SERT) to increase the synaptic concentrations of serotonin. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) is responsible for amyloid ß plaque formation. Hence it is an interesting target for Alzheimer's disease (AD) therapy. This study describes molecular interactions of a new Food and Drug Administration approved antidepressant drug named 'Fetzima' with BACE-1 and SERT. Fetzima is chemically known as levomilnacipran. The study has explored a possible link between the treatment of Depression and AD. 'Autodock 4.2' was used for docking study. The free energy of binding (ΔG) values for 'levomilnacipran-SERT' interaction and 'levomilnacipran-BACE1' interaction were found to be -7.47 and -8.25 kcal/mol, respectively. Levomilnacipran was found to interact with S438, known to be the most important amino acid residue of serotonin binding site of SERT during 'levomilnacipran-SERT' interaction. In the case of 'levomilnacipran-BACE1' interaction, levomilnacipran interacted with two very crucial aspartic acid residues of BACE-1, namely, D32 and D228. These residues are accountable for the cleavage of amyloid precursor protein and the subsequent formation of amyloid ß plaques in AD brain. Hence, Fetzima (levomilnacipran) might act as a potent dual inhibitor of SERT and BACE-1 and expected to form the basis of a future dual therapy against depression and AD. It is an established fact that development of AD is associated with Major Depressive Disorder. Therefore, the design of new BACE-1 inhibitors based on antidepressant drug scaffolds would be particularly beneficial.

Aptiom (eslicarbazepine acetate) as a dual inhibitor of ß-secretase and voltage-gated sodium channel: advancement in Alzheimer's disease-epilepsy linkage via an enzoinformatics study.

Neurodegenerative disorders are increasingly identified as one of the major causes of epilepsy. The relationship of epileptic activity to Alzheimer's disease (AD) is of clinical importance. Voltage-gated sodium channel (VSC) is one of the best targets in the treatment of epilepsy while ß-secretase (BACE) has long been observed as a curative target for AD. To explore a possible link between the treatment of AD and epilepsy, the molecular interactions of recently Food and Drug Administration approved antiepileptic drug Aptiom (Eslicarbazepine acetate) with BACE and VSC were studied. Docking study was performed using 'Autodock4.2'. Hydrophobic and pi-pi interactions play critical role in the correct positioning of Eslicarbazepine acetate within the catalytic site of VSC and BACE enzyme to permit docking. Free energy of binding (ΔG) of 'Eslicarbazepine acetate-VSC' interaction and 'Eslicarbazepine acetate-CAS domain of BACE' interaction was found to be -5.97 and -7.19 kcal/mol, respectively. Hence, Eslicarbazepine acetate might act as a potent dual inhibitor of BACE and VSC. However, scope still remains in the determination of the three-dimensional structure of BACE-Eslicarbazepine acetate and VSC-Eslicarbazepine acetate complexes by X-ray crystallography to validate the described data. Further, Aptiom (Eslicarbazepine acetate) could be expected to form the basis of future dual therapy against epilepsy associated neurological disorders.