Schizophrenia following new-onset refractory status epilepticus secondary to antiphospholipid syndrome

New-onset refractory status epilepticus (NORSE) is a drug-resistant status epilepticus that often has a catastrophic outcome. Our patient was diagnosed with NORSE and had an EEG reading that showed status epilepticus persisting for 8 months in general anesthesia. After autoimmune workup showed positive antiphospholipid antibodies, his seizure was controlled, and he was discharged with good condition apart from moderate cognitive impairment. However, he later developed schizophrenia. Although psychiatric disorders have been associated with antiphospholipid syndrome, to the best of our knowledge, it has not been reported to be associated with status epilepticus. We recommend vigilance of psychological complications of refractory status epilepticus’ patients for early psychiatric referral, diagnosis, and treatment.

New-onset refractory status epilepticus (NORSE) is a syndrome of new-onset drug-resistant status epilepticus that often has a catastrophic outcome. Epilepsy is usually associated with psychiatric disorders of different manifestations of which psychosis is an example.1 However, not much is found in the literature review regarding psychiatric disorders following NORSE although a recent study concluded 32% of NORSE patients ended up with altered behavioral states like aggression.2 Schizophrenia following NORSE like in the rare presentation of this case has not been reported in the literature review before, although an association between schizophrenia and autoimmune disorders like APS has been reported.3     

Modified stereotactic insertion of the Ommaya reservoir. Technical note

Ommaya reservoirs are used primarily for the repeated injection of intrathecal chemotherapy for leptomeningeal metastasis from hematopoietic and solid malignancies. Insertion of this device in a relatively large nondisplaced ventricle is not a difficult task, but challenges arise when the ventricle is small and/or displaced. Different techniques have been developed to overcome this difficulty, most of which include the use of stereotactic frames. Further improvements would be beneficial. The technique described in this paper depends on a stereotactic frame; however, the modification proposed by the authors removes the arc system from the surgical field before the actual surgical procedure is begun. Removal of the arc improves access to the surgical field as well as preparation and draping of the surgical site and minimizes potential breaks in sterile technique, which ultimately reduces the incidence of infection. A twist-drill hole along the path of the chosen trajectory becomes an external guide for the ventricular catheter. The technique is easy, user friendly, and results in an unencumbered sterile field and reliable cannulation of small ventricles. A simple stereotactic technique for Ommaya reservoir insertion has been described. It should lower the chance of infection in this group of patients, most of whom have suppressed immune systems.     

The Queuine Micronutrient: Charting a Course from Microbe to Man

Micronutrients from the diet and gut microbiota are essential to human health and wellbeing. Arguably, among the most intriguing and enigmatic of these micronutrients is queuine, an elaborate 7-deazaguanine derivative made exclusively by eubacteria and salvaged by animal, plant and fungal species. In eubacteria and eukaryotes, queuine is found as the sugar nucleotide queuosine within the anticodon loop of transfer RNA isoacceptors for the amino acids tyrosine, asparagine, aspartic acid and histidine. The physiological requirement for the ancient queuine molecule and queuosine modified transfer RNA has been the subject of varied scientific interrogations for over four decades, establishing relationships to development, proliferation, metabolism, cancer, and tyrosine biosynthesis in eukaryotes and to invasion and proliferation in pathogenic bacteria, in addition to ribosomal frameshifting in viruses. These varied effects may be rationalized by an important, if ill-defined, contribution to protein translation or may manifest from other presently unidentified mechanisms. This article will examine the current understanding of queuine uptake, tRNA incorporation and salvage by eukaryotic organisms and consider some of the physiological consequence arising from deficiency in this elusive and lesser-recognized micronutrient.     

Influence of <Emphasis Type="Italic">MX1</Emphasis> promoter rs2071430 G/T polymorphism on susceptibility to systemic lupus erythematosus

The expression of interferon inducible genes are reported to be heightened in systemic lupus erythematosus (SLE); nevertheless, not much is known regarding the genetic variants underlying these genes and their role in the pathogenesis of disease. Herein, we aim to explore the potential association and contribution of polymorphisms in MX1 gene (i) promoter with part of exon 1 (ii) intron 6, and (iii) their resulting haplotypes, with susceptibility to SLE. A total of 306 subjects, 152 SLE and 154 healthy controls (HC), were screened by direct sequencing method. Statistical analysis was carried out using appropriate software. The screening region of interest in MX1 revealed the existence of promoter (?123C/A, ?88G/T, ?20 A/C) and intron 6 (+9862G/A, +10190G/A, +9901C/G, +9920C/A, +9959C/T, +10047A/G) variants in SLE and HC. A significant association was observed between MX1 ?88G/T SNP and susceptibility to SLE (χ ²?=?4.18, p?=?0.04, OR?=?1.89, 95 % CI 1.03–3.5). Haplotype analysis also revealed increased risk of SLE among individuals carrying CTA haplotype (?123 C, ?88 T, ?20 A) (χ ²?=?5.74, p?=?0.017, OR?=?4.28, 95 % CI 1.30–14.06). None of the other tested variants showed any significant association with SLE. The present study is the first to reveal the influence of genetic variation in MX1 gene in susceptibility to SLE.     

Seizure semiology in temporal lobe vs. temporal plus epilepsy using intracranial EEG monitoring

Objectives:To utilize our tertiary center’s experience with Temporal lobe epilepsy (TLE) and Temporal plus epilepsy (TPE) cases and determine whether a correlation exists between ictal semiology signs, their localization/lateralization value after intracranial electroencephalography (EEG) monitoring, and surgical outcomes.Methods:A retrospective study was conducted among epilepsy patients who underwent resective surgery for TLE or TPE after intracranial EEG monitoring between January 2008 and December 2018 at King Faisal Specialist Hospital in Riyadh, Saudi Arabia. Data were retrieved for 464 patients; 181 had intracranial electrode monitoring.Results:Forty-eight patients with a mean age of 27 years (SD=8.4) were included; 15 patients had TPE. Auras were frequently reported, emotional auras, in the form of fear (35%). The localization/lateralization value of aura was statistically significant for TPE patients, including visual hallucinations and vertigo, lateralized to the left and right temporo-occipital, respectively (p=0.009 and <0.001). Early-onset ictal manual automatism, oral automatism, late-onset dystonic posture, and late head-turning were significant for TLE without significant lateralization value. The ictal onset zone’s localization was significant between the scalp and intracranial EEG findings in mesial TLE patients. The probability of seizure freedom (Engel class I) was 74%, 60%, and 67% at 2-year follow-up for mesial, lateral TLE, and TPE, respectively.Conclusion:Our results are consistent with previous studies and confirm the importance of ictal semiology signs in TLE and TPE. The addition of intracranial EEG monitoring in these cases helped improve the surgical outcomes.

Epilepsy is one of the most common neurological disorders, affecting approximately 70 million people globally.¹ Thirty percent of these patients have drug-resistant epilepsy,² and most cases referred for epilepsy surgery involve temporal lobe epilepsy (TLE).³ However, after standard temporal lobectomy, around 40% of these patients will experience recurrent seizures.⁴ A variety of explanations have been proposed for these surgical failures, including incomplete removal of the epileptogenic zone, additional contralateral focus (bilateral TLE), dual pathology (mesial and neocortical), and extended epileptogenic focus to the neighboring structures, including extratemporal or temporal plus epilepsy (TPE).⁵The TPE is defined as focal epilepsy with a complex epileptogenic network involving the temporal lobe and the surrounding areas, such as the orbitofrontal cortex, insula, operculum, and temporo-parieto-occipital junction.⁶ A thorough presurgical evaluation is required to delineate the epileptogenic zone for successful resective surgery. In phase I assessment, scalp video electroencephalography (EEG) monitoring, brain magnetic resonance imaging (MRI), and neuropsychological evaluation are needed. Further non-invasive investigations can be included if the initial results are discordant. To reach a well-demarcated epileptogenic focus requires intracranial monitoring, including the subdural grid, strips, and depth, which is known as phase II assessment.⁷ Seizure semiology is the first step in a presurgical evaluation, and ictal semiology and scalp-EEG results play a valuable role in distinguishing TLE from TPE.⁸ Patients with TLE are more likely to experience abdominal auras, ictal gestural automatism, and post-ictal amnesia. However, TPE patients are more likely to experience gustatory hallucinations, rotatory vertigo, auditory illusions, contralateral eye and head versions, piloerection, and ipsilateral tonic posturing. Similar findings were highlighted in a review of TPE cases.4 Furthermore, laryngeal and throat constriction and the atypical distribution of somatosensory symptoms at seizure onset have been found.4Although some studies have found a correlation between seizure semiology and intracranial EEG monitoring in TLE (mesial vs. lateral) vs. TPE, none evaluated lateralization values. This study aims to utilize our tertiary center’s experience with TLE and TPE cases and determine whether a correlation exists between ictal semiology signs, their localization/lateralization value after intracranial electroencephalography (EEG) monitoring and surgical outcomes. We also highlight the process of phase I presurgical assessment (including ictal/interictal scalp EEG, MRI, positron emission tomography [PET], and neuropsychology) in our center.     

Camel Urine Promotes Sensitization to Doxorubicin by Inhibiting Epithelial-Mesenchymal Transition and Modulating NF-κB-Snail Signaling Pathway in Breast Cancer Cells

Background:Camel urine (CU) has been used as traditional treatment in the Arabian Peninsula for centuries. Although, researchers have reported CU anti-cancer effects, the exact mechanism(s) of action involved has not been fully elucidated. The epithelial–mesenchymal transition EMT is a phenotypic switch that promotes the acquisition of a fibroblastoid-like morphology by epithelial tumor cells, resulting in enhanced tumor cell motility and invasiveness. EMT has been shown to contribute to metastasis and chemoresistance of carcinomas. For that, in the present study, we have assessed the potential mechanism (s) by which CU exert its anti-cancer effects and its possible synergistic therapeutic effect with Doxorubicin (DOX) in breast cancer cells. Methods:Determination of anti-proliferative and apoptosis validation of CU was performed by 3-(4,5-Dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT), annexin-V-fluorescein isothiocyanate assays, and Western blot. EMT protein markers, migration and invasion of cells were determined by Western blot or immunofluorescent staining, Scratch assay, Transwell invasion assay, respectively. Results:CU applied a significant anti-cancer effect on breast cancer cells via induction of DNA damage and apoptosis in a concentration- and time-dependent manner. Also, CU remarkably reversed the EMT by downregulating N-cadherin and Vimentin expression and upregulating E-cadherin expression. As a result, the stemness, migration and invasion of breast cancer cells were also inhibited, which was likely mediated by NF-κB-Snail signalling pathway and its downstream inflammatory effectors. CU successfully enhanced DOX cytotoxicity by reversing EMT which possibly through inhibition of NF-κB-Snail signalling and subsequently inflammation. Thus, our study provides new mechanistic bases for the therapeutic application of CU that may improve the outcomes of anti-cancer chemotherapy.Key Words: Chemoresistance, camel urine, breast cancer, NF-κB, EMT     

Effect of varicella zoster virus infection on bone marrow function

BACKGROUND: Most viral infections are known to exert adverse effects on bone marrow function. However, certain viruses have recently been found to be therapeutically beneficial in the treatment of some malignant disorders. METHODS AND MATERIALS: A retrospective study was conducted at the Armed Forces Hospital, Riyadh, Saudi Arabia. The changes in the hematological parameters following varicella-zoster virus (VZV) infection in patients with a variety of hematological disorders were compared with those in a control group having the same spectrum of disorders and treated in the same unit over the same period of time but never had VZV infection. Both groups of patients received the same treatment protocols for their primary hematological disorders. Definitive treatment (DT) such as chemotherapy alone, anti-thymocyte globulin or bone marrow transplant was also employed in the management of patients belonging to both groups. RESULTS: White blood cell counts, platelet counts and hemoglobin concentrations in the study group started to increase 40 d after chickenpox or herpes zoster infection and these increases lasted for periods as long as 1050 d. The changes in platelet counts were more pronounced than those in other hematological parameters. There was a significant difference (P < 0.0001) between the two groups of patients in the values of platelet counts achieved between 280 and 1050 d after DT (mean platelet count: 262 x 10(9)/L in the study group vs. 180 x 10(9)/L in the control group, median: 288.17 x 10(9)/L in the study group vs. 180 x 10(9)/L in the control group, range: 102 to 415 x 10(9)/L in the study group vs. 26 to 365 x 10(9)/L in the control group of patients). Compared to the control group, the study group of patients achieved their maximum blood counts much earlier after DT. The maximum leucocytic count was achieved at a mean duration of 269.21 d in the study group and 349.61 d in the control group. The maximum hemoglobin level was achieved at a mean duration of 319.5 d in the study group and 402.6 d in the control group. The maximum platelet count was achieved at a mean duration of 271.4 d in the study group and 318.9 d in the control group of patients. CONCLUSION: VZV may behave differently from other members of the herpes group of viruses e.g. human cytomegalovirus and Epstein-Barr virus. Our observations suggest that VZV infection causes stimulation of bone marrow activity.