Development of HPLC-UV method for rapid and sensitive analysis of topically applied tetracaine: its comparison with a CZE method.

Topically applied tetracaine is a local anaesthetic. A novel HPLC method for the rapid and sensitive analysis of tetracaine was developed and compared with a short end direction capillary zone electrophoresis (CZE) method. The method was developed and validated for the separation and quantification of tetracaine in skin samples removed by 'tape-stripping'. Tetracaine was extracted from tape with 100% methanol, which was then diluted to 50% with water for injection. Tetracaine and the internal standard, procaine, were separated on a reversed-phase Luna PFP(2), 3 µm, 150 × 4.6 mm column at ambient temperature using isocratic elution with KH2 PO4 buffer (pH 2.5) and methanol (35:65, v/v). The flow rate was 1 mL/min, with detection at 312 nm. The limit of quantification for tetracaine was 0.03 µg/mL. Calibration lines were linear with r(2) values >0.99. The within- and between-assay imprecision and the percentage of inaccuracy for the QC samples including lower and upper limits of quantitation were <6 and <10%. The absolute mean recovery of tetracaine was >92%. Compared with CZE, the mean percentage error and the absolute mean percentage error were 0.62 and 6.29, respectively. The two methods were compared in a number of pharmacokinetic studies.

Current practice and safety measures in epilepsy monitoring units in the Gulf Cooperation Council Countries: A cross-sectional study.

BACKGROUND: An increasing number of Epilepsy Monitoring Units (EMU) display various practices and safety protocols. EMU settings should meet clear, standardized safety protocols to avoid seizure adverse events (SAE). We aim to provide the foundational framework facilitating the establishment of unified evidence-based safety regulations to address the practices and safety measures implemented within the Gulf Cooperation Council (GCC). METHODS: In this cross-sectional study, EMU directors in the GCC were contacted directly by phone to personally complete an electronic 37-item questionnaire sent via text messages and email. From January 2021-December 2021. RESULTS: Seventeen EMUs from six GCC countries participated in the study. All EMU directors responded to the study. Twelve (70.6%) EMUs monitored adults and children, five (29.4%) monitored adults, and none monitored children only. The number of certified epileptologists in the EMUs ranged from one to eight per unit. Fifteen (88.2%) EMUs applied a continuous observation pattern, whereas two (11.8%) performed daytime only. The precautions most commonly used in the video Electroencephalogram (EEG) were seizure pads and bedside oxygen in 15 EMUs (88.2%). For invasive EEG, seizure pads were used in 9 EMUs (52.9%), %) and IV access in 8 EMUs (47.1%). The occurrence of adverse events varied among EMUs. The most common conditions were postictal psychosis 10 (58.8%), injuries 7 (41.2%), and status epilepticus 6 (35.3%). Falls were mainly related to missed seizures or delayed recognition by video monitors in 8 EMUs (47.1%). The extended EMU stay was because of an insufficient number of recorded seizures in 16 EMUs (94.1%), poor seizure lateralization and localization in 10 (58.8%), and re-introduction of AEDs in nine (52.9%). All EMUs had written acute seizure and status epilepticus management protocols. A postictal psychosis management protocol was available for 10 (58.8%). Medications were withdrawn before admission in 6 EMUs (35.3%). The specific medication withdrawal speed protocol upon admission was available in 7 EMUs (41.2%). Pre-admission withdrawal of medication demonstrated a shorter length of stay in both video and invasive EEG, which was statistically significant (ρ (15) = -.529, p =.029; ρ (7) = -.694, p =.038; respectively). CONCLUSION: The practice and safety regulations of EMUs in the GCC vary widely. Each EMU reported the occurrences of SAE and injuries. Precautions, protective measures, and management protocols must be reassessed to minimize the number of SAEs and increase the safety of the EMU.

Structural and energetic analysis of NS5 protein inhibition by small molecules in Japanese encephalitis virus using machine learning and steered molecular dynamics approach.

One of the viral diseases that affect millions of people around the world, particularly in developing countries, is Japanese encephalitis (JE). In this study, the conserved protein of this virus, that is, non-structural protein 5 (NS5), was used as a target protein for this study, and a compound library of 749 antiviral molecules was screened against NS5. The current study employed machine learning-based virtual screening combined with molecular docking. Here, three hits (24360, 123519051 and 213039) had lower binding energies (< -8 kcal/mol) than the control, S-Adenosyl-L-homocysteine (SAH). All the compounds showed significant H-bond interactions with functional residues, which were also observed by the control. Molecular dynamics simulation, MM/GBSA for binding free energy analysis, principal component analysis and free energy landscape were also performed to study the stability of the complex formation. All three compounds had similar root mean square deviation trends, which were comparable to the control, SAH. Post-MD, the 123519051-receptor complex had the highest number of H-bonds (4 to 5) after the control, out of which three exhibited the highest percentage occupancy (50%, 24% and 79%). Both docking and MD, 123519051 showed an H-bond with the residue Gly111, which was also found for the control-protein complex. 123519051 showed the lowest binding free energy with ΔGbind of -89 kJ/mol. Steered molecular dynamics depicted that 123519051 had the maximum magnitude of dissociation (1436.43 kJ/mol/nm), which was more than the control, validating its stable complex formation. This study concluded that 123519051 is a binder and could inhibit the protein NS5 of JE.Communicated by Ramaswamy H. Sarma.

Non-Invasive Brain Sensing Technologies for Modulation of Neurological Disorders.

The non-invasive brain sensing modulation technology field is experiencing rapid development, with new techniques constantly emerging. This study delves into the field of non-invasive brain neuromodulation, a safer and potentially effective approach for treating a spectrum of neurological and psychiatric disorders. Unlike traditional deep brain stimulation (DBS) surgery, non-invasive techniques employ ultrasound, electrical currents, and electromagnetic field stimulation to stimulate the brain from outside the skull, thereby eliminating surgery risks and enhancing patient comfort. This study explores the mechanisms of various modalities, including transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), highlighting their potential to address chronic pain, anxiety, Parkinson's disease, and depression. We also probe into the concept of closed-loop neuromodulation, which personalizes stimulation based on real-time brain activity. While we acknowledge the limitations of current technologies, our study concludes by proposing future research avenues to advance this rapidly evolving field with its immense potential to revolutionize neurological and psychiatric care and lay the foundation for the continuing advancement of innovative non-invasive brain sensing technologies.

Functional neurosurgery. The modulation of neural and mind circuits.

Different complex neuroanatomical and neurochemical circuits regulate a variety of neuronal behaviors and brain functions. Any disturbance in these circuits can generate functional disorders such as movement disorders, epilepsy, pain, memory disorders, and psychiatric disorders. Functional neurosurgery aims to restore these functions, either by removing or isolating the abnormally behaving neurons or by modulating the disturbed circuits. Neuromodulation is a fast-growing field, powered by the recent advances in neuroimaging and technology. Here, we discuss recent advances and new horizons in functional neurosurgery.

Safety and Efficacy of Clonazepam in the Treatment of Juvenile Myoclonic Epilepsy: A Meta-Analysis.

Background: Juvenile myoclonic epilepsy (JME) is referred to as one of the most common epileptic syndromes. Several anti-epilepsy drugs (AEDs) have been developed and remain part of clinical intervention with varying safety and efficacy profiles. Comprehensive synthesis of the scientific evidence examining the safety and efficacy of clonazepam toward the treatment of JME was carried out in the study. Methods: A detailed scientific literature search was made utilizing the most relevant scientific studies published to date on the intervention of clonazepam in the management of JME. In this study, a detailed search was made in multiple databases, including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scielo databases. Confidence intervals among the studies and continuous measures, proportion, and risk factor analysis were determined using the MedCalC tool (Version 20.110) as per PRISMA guidelines. Results: A total of 6 studies out of 70 were found eligible for meta-analysis, where 186 JME patients were subjected to clonazepam intervention with controls. Clonazepam was reported effective in comparative analysis among six studies where P < 0.001. The result also shows a higher prevalence of JME in the female population compared to males (male versus female; 86/110). Efficacy and safety of clonazepam were reported significant as well. Conclusion: Clonazepam is effective AEDs for the management of JME. However, more clinical evidence requires for statistical validation of clinical efficacy.

Stuttered swallowing: electric stimulation of the right insula interferes with water swallowing. A case report.

BACKGROUND: Various functional resonance imaging, magnetoencephalographic and lesion studies suggest the involvement of the insular cortex in the control of swallowing. However, the exact location of insular activation during swallowing and its functional significance remain unclear. CASE PRESENTATION: Invasive electroencephalographic monitoring was performed in a 24-year-old man with medically intractable stereotyped nocturnal hypermotor seizures due to a ganglioglioma. During stimulation of the right inferior posterior insular cortex with depth electrodes the patient spontaneously reported a perception of a "stutter in swallowing". Stimulation of the inferior posterior insular cortex at highest intensity (4 mA) was also associated with irregular and delayed swallows. Swallowing was not impaired during stimulation of the superior posterior insular cortex, regardless of stimulation intensity. CONCLUSIONS: These results indicate that the right inferior posterior insular cortex is involved in the neural circuitry underlying the control of swallowing.

The cardioinhibitory responses of the right posterior insular cortex in an epileptic patient.

BACKGROUND: The insular cortex (IC) has long been implicated in the central regulation of the autonomic nervous system but its precise role remains to be determined. We studied the role of IC in cardiovascular control using a multimodality approach consisting of isometric handgrip exercises, functional magnetic resonance imaging (fMRI) activation during handgrip exercises, and direct electrical stimulations of the posterior right IC in a single patient. METHOD: A 24-year-old patient had medically intractable epilepsy secondary to a small ganglioglioma in the right posterior IC. His cardiovascular responses to 30 and 70% maximum voluntary contraction (MVC) handgrip exercises were recorded in the lab and during fMRI and compared to those of 10 healthy control subjects. He subsequently underwent stereo-electroencephalography with depth electrodes in the right posterior IC and further study of the cardiovascular responses to electrical stimulation at rest and during MVC handgrip exercises. RESULT: fMRI data showed nearly absent activation in the right IC relative to healthy subjects. At rest, electrical stimulation of the right posterior inferior IC but not the superior IC suppressed heart rate (HR) by 3 beats per minute. During exercise, the HR response to isometric handgrip contraction was weakened when the right posterior inferior IC was simultaneously stimulated. CONCLUSION: This study shows that, in this patient, the right posterior inferior IC is an important cardioinhibitory center and interference with this region alters the cardiac response to handgrip exercise. Further investigations are required to examine the cardiovascular control of the IC.

Novel SARS-CoV-2 outbreak and COVID19 disease; a systemic review on the global pandemic.

Since the beginning of the 21st century, several viral outbreaks have threatened humankind and posed a new challenge to the modern healthcare system. The recent outbreak in Wuhan (December 2019), China, represents a beta coronavirus classified as novel Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) which belongs to the Coronaviridae family. Novel SARS-CoV-2 represents a significant similarity with previous coronaviruses such as SARS-CoV in 2002, China and MERS-CoV in 2015, Middle East. However, preliminary research investigations have shown the novel SARS-CoV-2 evolved with several mutations and developed the capacity to cross the species, i.e., animal to human. The initial findings have shown that spike proteins are vital molecules target hACE2 receptor for its attachment and entry into cells. After successful entry virus primarily focuses on respiratory airway cell lines and triggers a massive immune response leading to mucus generation. In severe conditions, the virus is capable of forcing viral pneumonia leading to the collapse of the respiratory system, i.e., COVID19. So far, there is a lack of immunity against the virus in humans. At the same in the absence of therapeutic interventions, many countries experienced high mortality, such as the United States, European countries, i.e., Italy, Spain, France, and the United Kingdom. The vaccine development is underway and experiencing challenges, as many reports demonstrated genetic variations in viral genome and proteins as well. The present study provides a complete comprehensive overview of the novel SARS-CoV-2 outbreak, human transmission, and global spread.

Utility of single-photon emission computed tomography (SPECT) in presurgical evaluation of children: A single-center experience.

OBJECTIVE: Single-photon emission computed tomography (SPECT) is an ancillary noninvasive test commonly used to identify the epileptogenic zone. However, its proper utilization may be limited depending on the resources available at each center. This study aimed to investigate the utility of SPECT in presurgical evaluation of children at our center. METHODS: This was an observational retrospective study in 150 children who were admitted to the Epilepsy Monitoring Unit for presurgical evaluation between 2012 and 2019. The utility of interictal and ictal SPECT in different clinical cohorts was analyzed. RESULTS: Only interictal SPECT was performed on 87 patients (58 %), while ictal SPECT was performed on 62 (41.3 %), and interictal SPECT alone was considered of low diagnostic value. Ictal SPECT was unremarkable in 27 of 62 patients and abnormal in 35. Ictal SPECT was localized to the temporal lobe in 62.8 % and to the extratemporal lobe in 25.7 % of the patients and lateralized to one hemisphere in 11.4 % of the patients. In the abnormal SPECT group, ictal SPECT was considered unnecessary in 7/35 (20 %) patients with a single lesion and 3/35 (8.5 %) patients with a hemispheric lesion. In the remaining 25 patients, surgery was recommended more frequently than invasive EEG monitoring (IEM) for diffuse lesion cases (P = 0.03), while IEM was recommended more frequently than surgery for MRI-negative cases (P = 0.03), and in this group none of the MRI-negative patients underwent surgery. In our entire cohort, epilepsy surgery was performed on 24.4 % of the patients, 64 % with a single lesion, 7.6 % with a hemispheric lesion, 25.6 % with a diffuse lesion, and only one MRI-negative patient (2.5 %). Surgery was performed in 48.7 % of single lesion cases and 20.5 % of diffuse lesion cases with either unremarkable or no ictal SPECT. Engel class I outcome was achieved in 62 % and class II outcome in 33 % of the patients. In the single lesion etiology, 72 % (18/25) patients achieved excellent outcome and within this group, 22 % (4/18) patients had a positive ictal SPECT whereas 78 % (14/18) patients either did not get an ictal SPECT or it was unremarkable. SIGNIFICANCE: Based on our findings, we suggest carefully selecting patients for SPECT imaging to improve its utility and prevent overutilization and potential harm to children.

An overview of structurally diversified anticonvulsant agents.

There are several limited approaches to treat epilepsy in hospitals, for example, using medicines, surgery, electrical stimulation and dietary interventions. Despite the availability of all these new and old approaches, seizure is particularly difficult to manage. The quest for new antiepileptic molecules with more specificity and less CNS toxicity continues for medicinal chemists until a new and ideal drug arrives. This review covers new antiseizure molecules of different chemical classes, the exact mode of action of which is still unidentified. Newer agents include sulfonamides, thiadiazoles, semi- and thiosemicarbazones, pyrrolidine-2,5-diones, imidazoles, benzothiazoles and amino acid deriva tives. These new chemical entities can be useful for the design and development of forthcoming antiseizure agents.

Diagnostic yield of stereotactic brain biopsy.

OBJECTIVE: To evaluate the diagnostic yield, accuracy, and safety of frame-based stereotactic brain biopsy procedures. METHODS: A retrospective study of all pathologically diagnosed intracranial lesions, using frame-based stereotactic guided brain biopsy procedures performed at King Faisal Specialist Hospital and Research Centre (KFSH&RC), Riyadh, Kingdom of Saudi Arabia between 1993 and 2005 was conducted. Medical charts, radiological studies, and pathological slides were reviewed. RESULTS: A total of 120 consecutive patients who had frame-based stereotactic diagnostic biopsy procedures were identified. Data regarding procedural techniques, lesion locations, pathological diagnosis, and postoperative complications were collected. Patients` ages ranged from 3-72 years (mean +/- standard deviation: 39.4 +/- 20.3), 67 males and 53 females. Sites of biopsied lesions included: 49 thalamic, 29 deep frontal, 23 parietal, 9 temporal, and 10 others. Targeting accuracy was 99.2%. General anesthesia was used in 103 patients (85.8%). The rest was carried out under local anesthesia. Diagnostic yield was estimated at 96%. Most frequently encountered pathological diagnosis includes gliomas (63%), infections (16%), and lymphomas (7%). One mortality (0.8%), and 5 (4%) morbidities were encountered. CONCLUSION: Stereotactic brain biopsy is a relatively safe technique to obtain a tissue biopsy that represents the pathology of the lesion. Recent advances in stereotactic neurosurgical techniques have helped to improve the safety and diagnostic yield of such procedures.

Herbal medicines: Saudi population knowledge, attitude, and practice at a glance.

Herbal medicines are widely used in many countries in preventing and treating health disorders. In this study, a multiregional cross-sectional survey, a random sample of 809 adults from Saudi Arabia and territories were used to explore the participants' knowledge, attitude, and practice regarding the use of tradition medicines in Saudi society. Data were collected through direct simple observation, interviews, and structured questionnaires. Observations were made and interviews conducted in public places such as markets and popular schools. The questionnaire included data on sociodemographic such as age and gender and was drafted with optional questions and predefined answer. Data were collected from May 1st to the end of July 2014. Most of the respondents were female (85%). Approximately 70% of participants were found to be highly knowledgeable about the use of herbal medicine. The study found that 88.4% of the respondents stated to have used herbal medicines and 84.3% were interested in traditional recipes. Most of the participants used it for therapeutic reason (88.7%), with a successful effectiveness of 61.2%. In addition, the study found that 48.2% of the participants were taking information from friends and 76% stated that they do not trust the published information in commercial channels. Statistical analysis showed an association between the perception and the demographic data, with an increase in the use of herbal medicines. Because of the increased use of herbal medicine in Saudi Arabia facilitated by perceptions and attitudes of the population, it is important to ensure standardization, stability, and quality control of the use of medicine in Saudi Arabia.

Prevalence of obstructive sleep apnea in children with sickle cell disease at a tertiary hospital in Saudi Arabia.

OBJECTIVES: To assess the prevalence of obstructive sleep apnea in Saudi children with sickle cell disease at a tertiary hospital in Kingdom of Saudi Arabia (KSA) using nocturnal polysomnography. Methods: A prospective cross-section study was conducted between 2012 and 2016 in 65 children aged between 2-14 years at Prince Sultan Military Medical City, Riyadh, KSA with sickle cell disease. Patients answered a pediatric sleep questionnaire with the help of an accompanying caregiver and underwent polysomnography in the same night. Results: The final sample included 65 children. Median age was 8.1 years. There were 32 boys (49.2%) and 33 girls (50.8%). Mean hemoglobin was 8.6 (p=0.37) and mean body mass index was 15.6 (p=0.36). The prevalence of obstructive sleep apnea was 80% (52 patients) using an apnea hypopnea index cutoff of ≥1 and 7.7% (5 patients) using an apnea hypopnea index cutoff of ≥5. Results from the pediatric sleep questionnaire were snoring (73.8%), apnea (32.8%), and bedwetting (46%). Conclusion: Obstructive sleep apnea is common in children with sickle cell disease.

Miliary tuberculomas of the brain: case report.

Tuberculosis (TB) of the central nervous system (CNS) is still prevalent in many developing countries. Tuberculoma is always considered in the differential diagnosis of enhancing intra-axial lesions of the brain. Brain tuberculomas can present in many different clinical and radiological patterns, disseminated or miliary brain tuberculomas are very rare. We describe the case of a 25-year-old immunocompetent female with miliary brain tuberculomas. She presented with a history of progressive headache and unsteady gait. Serial Magnetic resonance imaging (MRI) studies revealed growing, multiple small enhancing lesions in the brain, most lesions measured approximately 2mm in diameter, in both the supratentorial and infratentorial compartments. Her investigation failed to reveal any evidence of TB outside the CNS. Open biopsy revealed multiple caseating granulomas and mycobacterin tuberculosis was cultured. She improved clinically and radiologically after starting anti-tuberculous pharmacotherapy. The clinical course, radiological images and pathological studies of this patient are presented. In conclusion miliary brain tuberculomas are rare and unique clinical and radiological entity. It may affect immunocompetent individuals with no other signs of other systemic involvement.

Type I congenital multiple intraspinal extradural cysts associated with distichiasis and lymphedema syndrome.

OBJECTIVE: The hereditary syndrome of multiple congenital intraspinal cysts associated with distichiasis, lymphedema and other congenital deformities is extremely rare. Modern imaging techniques have promoted the non-invasive diagnosis of spinal pathology and paved the way for better surgical planning. We reviewed the clinical data, imaging studies and treatment outcomes of a 12-year-old boy with this syndrome. CLINICAL PRESENTATION: Progressive spastic paraparesis with signs of spinal cord compression leading to frequent falls. This was associated with bilateral double row of eyelashes and pretibial edema. The MRI of thoracic spine depicted two large elongated extradural lesions extending from D5-D10 with signal intensity compatible with cerebrospinal fluid leading to severe compression of the spinal cord dorsally. TREATMENT: Laminotomy and complete microsurgical excision of the cysts resulted in a fast and full clinical recovery of his neurological deficit. CONCLUSION: Type I congenital intraspinal cysts is a rare etiology of cord compression syndrome and may be associated with distichiasis, lymphedema and other congenital deformaties. It has several characteristics, which include the higher incidence in thoracic spine and younger age group, disproportional sever motor deficit as compared with sensory disturbances and the excellent clinical recovery following successful surgical treatment.

Microvascular Decompression for Oculomotor Nerve Palsy: A Case Report and Literature Review.

BACKGROUND: Oculomotor nerve palsy can result as a manifestation of diabetic mellitus or aneurysmal compression. Vascular loop compression is a very rare etiology of oculomotor nerve palsy. Here, we present a case report of microvascular decompression for oculomotor nerve palsy. CASE DESCRIPTION: We present a 16-year-old male patient, otherwise healthy, who presented with right oculomotor nerve palsy for a period of 1 year. Aneurysmal compression and intracranial lesion were ruled out by cerebral angiogram and magnetic resonance imaging. The presence of vessel loop compression on the nerve was suspected on the basis of features on magnetic resonance imaging. The patient underwent microvascular decompression via a right subtemporal approach. We intraoperatively confirmed vessel loop compression at the exit zone of the nerve from midbrain. Subsequently, the patient's oculomotor palsy has improved gradually over a period of 6 months. CONCLUSIONS: Vascular compression of the oculomotor nerve is a very rare finding in neurosurgical practice. A diagnosis of vascular compression is made by excluding other pathologies and using high-resolution images that visualize the nerve and the offending vessel loop. Microvascular decompression can be an effective treatment method for this condition.

Giant orbitoethmoidal osteoma: when an open surgical approach is required.

Giant orbitoethmoidal osteoma in children is considered to be rare. This type of pathology can be associated with significant disfiguring proptosis and limitation of eye movement. Here, we report on a child who presented with a giant orbitoethmoidal osteoma that was removed through an orbitofrontal approach. The cosmetic result was excellent and evident immediately after surgery. A review of the literature complements this report.

Minicraniotomy for standard temporal lobectomy: a minimally invasive surgical approach.

Introduction. The common surgical approach for standard temporal lobectomy is a question-mark skin incision and a frontotemporal craniotomy. Herein, we describe minicraniotomy approach through a linear skin incision for standard temporal lobectomy. Methods. A retrospective observational cohort study was conducted for a group of consecutive 21 adult patients (group I) who underwent minicraniotomy for standard temporal lobectomy utilizing a linear skin incision. This group was compared to a consecutive 17 adult patients (group II) who previously underwent a reverse question-mark skin incision and standard frontotemporal craniotomy. Results. The mean age was 29 and 23 for groups I and II, respectively. The mean estimated blood loss was 190 mL and 280 mL in groups I and II, respectively (P = 0.019). Three patients in group II developed chronic postcraniotomy headache compared to none in group I. Cosmetic outcome was excellent in group I while 4 patients in group II developed disfiguring depression at lateral sphenoid wing and anterior temple. In group I 17 out of 21 became seizure-free at one-year followup. Conclusion. Minicraniotomy through a linear skin incision is a sufficient surgical approach for effective standard temporal lobectomy and it has an excellent cosmetic outcome.