Concurrent Longitudinal Extensive Transverse Myelitis and Leptomeningitis in West Nile Virus: A Report of a Rare Case.

Here we report a rare case with concurrent longitudinal extensive transverse myelitis (LETM) and leptomeningitis due to West Nile virus infection. A 47-year-old man initially presented with a six-day progressive, intermittent low-grade fever, headache, diplopia, malaise, myalgia, lower back pain, and difficulty walking that developed into progressive asymmetric paralysis. Initial lab work was notable for mild lactic acidosis and hyperCKemia. Brain MRI with contrast demonstrated small foci of leptomeningeal enhancement in the cerebellum, pons, medulla, and right CN VI at the cisternal segment. MRI of the spine was remarkable for edema in the spinal cord extending from T10 to L1 with diffuse enlargement of the cord contour at T11 to L1 and subtle enhancement of nerve roots within the thecal sac and cauda equina regions. The patient responded partially to five-day intravenous immunoglobulin therapy (total dose, 2 g/kg). Electromyography four months after the onset of symptoms also showed chronic reinnervation with active denervating features in thoracolumbar myotomes. Clinically, this case highlights the ill-defined and non-specific nature of the presentation of West Nile neuroinvasive disease. It can pose a diagnostic challenge for clinicians and, if unrecognized, is associated with significant morbidity and mortality in older and compromised individuals.

Protective Effects of Glatiramer Acetate Against Paclitaxel-Induced Peripheral Neuropathy in Rats: A Role for Inflammatory Cytokines and Oxidative Stress.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major challenge for cancer patients who undergo chemotherapy with paclitaxel. Therefore, finding effective therapies for CIPN is crucial. Glatiramer acetate is used to treat multiple sclerosis that exerts neuroprotective properties in various studies. We hypothesized that glatiramer acetate could also improve the paclitaxel-induced peripheral neuropathy. We used a rat model of paclitaxel (2 mg/kg/every other day for 7 doses)-induced peripheral neuropathy. Rats were treated with either different doses of glatiramer acetate (1, 2, 4 mg/kg/day) or its vehicle for 14 days in separate groups. The mechanical and thermal sensitivity of the rats by using the Von Frey test and the Hot Plate test, respectively, were assessed during the study. The levels of oxidative stress (malondialdehyde and superoxide dismutase), inflammatory markers (TNF-α, IL-10, NF-kB), and nerve damage (H&E and S100B staining) in the sciatic nerves of the rats were also measured at the end of study. Glatiramer acetate (2 and 4 mg/kg) exerted beneficial effects on thermal and mechanical allodynia tests. It also modulated the inflammatory response by reducing TNF-α and NF-κB levels, enhancing IL-10 production, and improving the oxidative stress status by lowering malondialdehyde and increasing superoxide dismutase activity in the sciatic nerve of the rats. Furthermore, glatiramer acetate enhanced nerve conduction velocity in all treatment groups. Histological analysis revealed that glatiramer acetate (2 and 4 mg/kg) prevented paclitaxel-induced damage to the nerve structure. These results suggest that glatiramer acetate can alleviate the peripheral neuropathy induced by paclitaxel.

Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. CONCLUSION: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

Miller-Fisher Syndrome With Initial Manifestation of Rhinolalia Aperta: A Case Report and Literature Review.

Rhinolalia aperta (hypernasal speech) is rarely reported in patients with Miller-Fisher syndrome (MFS). Here, we report a patient with MFS who presented with rhinolalia aperta. A 35-year-old man with a history of alcohol abuse and hepatic cirrhosis presented with a three-day acute hypernasal voice change and numbness of both hands/thighs. After admission, the exam also revealed palatal hypomobility, decreased bilateral hand/thigh sensation, ataxic gait, dysmetria, areflexia, and bilateral abducens palsy. Serum immunoglobulin G (IgG) anti-GQ1b antibody titer was elevated (1:6400). A five-day intravenous IgG was administered with a robust clinical response. Oropharyngeal involvement in MFS can initially manifest with isolated hypernasal speech.

Kynurenine pathway and its role in neurologic, psychiatric, and inflammatory bowel diseases.

Tryptophan metabolism along the kynurenine pathway is of central importance for the immune function. It prevents hyperinflammation and induces long-term immune tolerance. Accumulating evidence also demonstrates cytoprotective and immunomodulatory properties of kynurenine pathway in conditions affecting either central or peripheral nervous system as well as other conditions such as inflammatory bowel disease (IBD). Although multilevel association exists between the inflammatory bowel disease (IBD) and various neurologic (e.g., neurodegenerative) disorders, it is believed that the kynurenine pathway plays a pivotal role in the development of both IBD and neurodegenerative disorders. In this setting, there is strong evidence linking the gut-brain axis with intestinal dysfunctions including IBD which is consistent with the fact that the risk of neurodegenerative diseases is higher in IBD patients. This review aims to highlight the role of kynurenine metabolic pathway in various neurologic and psychiatric diseases as well as relationship between IBD and neurodegenerative disorders in the light of the kynurenine metabolic pathway.

Interfacial Tension-Temperature-Pressure-Salinity Relationship for the Hydrogen-Brine System under Reservoir Conditions: Integration of Molecular Dynamics and Machine Learning.

Hydrogen (H2) underground storage has attracted considerable attention as a potentially efficient strategy for the large-scale storage of H2. Nevertheless, successful execution and long-term storage and withdrawal of H2 necessitate a thorough understanding of the physical and chemical properties of H2 in contact with the resident fluids. As capillary forces control H2 migration and trapping in a subsurface environment, quantifying the interfacial tension (IFT) between H2 and the resident fluids in the subsurface is important. In this study, molecular dynamics (MD) simulation was employed to develop a data set for the IFT of H2-brine systems under a wide range of thermodynamic conditions (298-373 K temperatures and 1-30 MPa pressures) and NaCl salinities (0-5.02 mol·kg-1). For the first time to our knowledge, a comprehensive assessment was carried out to introduce the most accurate force field combination for H2-brine systems in predicting interfacial properties with an absolute relative deviation (ARD) of less than 3% compared with the experimental data. In addition, the effect of the cation type was investigated for brines containing NaCl, KCl, CaCl2, and MgCl2. Our results show that H2-brine IFT decreases with increasing temperature under any pressure condition, while higher NaCl salinity increases the IFT. A slight decrease in IFT occurs when the pressure increases. Under the impact of cation type, Ca2+ can increase IFT values more than others, i.e., up to 12% with respect to KCl. In the last step, the predicted IFT data set was used to provide a reliable correlation using machine learning (ML). Three white-box ML approaches of the group method of data handling (GMDH), gene expression programming (GEP), and genetic programming (GP) were applied. GP demonstrates the most accurate correlation with a coefficient of determination (R2) and absolute average relative deviation (AARD) of 0.9783 and 0.9767%, respectively.

A single-center retrospective study of hospitalized COVID-19 patients: demographics, laboratory markers, neurological complications, ICU admission, and mortality.

The coronavirus disease 2019 (COVID-19) pandemic has unveiled a wide array of clinical biomarkers, and neurological manifestations in affected patients, necessitating further exploration. Methods: This single-center retrospective study evaluated clinical and neurological sequelae, demographics, as well as laboratory markers, in hospitalized COVID-19 patients from January to September 2020. Results: Among 1248 inpatients (median age: 68 years; 651 women), 387 (31%) were admitted to the ICU. Central nervous system (CNS) manifestations were present in 521 (41.74%) patients, while peripheral nervous system manifestations were observed in 84 (6.73%). COVID-19-related mortality occurred in 314 (25.16%) cases. ICU-admitted patients were predominantly male (P<0.0001), older (age≥60; P=0.037) and had more comorbidities such as diabetes (P=0.001), hyperlipidemia (P=0.043), and coronary artery disease (P=0.015). ICU patients exhibited more CNS manifestations (P=0.001), including impaired consciousness (P<0.0001) and acute cerebrovascular disease (P=0.023). Biomarkers linked to admission to the ICU included elevated white blood cell count, ferritin, lactate dehydrogenase, creatine kinase, blood urea nitrogen, creatinine, and acute phase reactants (e.g. erythrocyte sedimentation rate and C-reactive protein). ICU patients demonstrated lower lymphocyte and platelet counts compared to non-ICU patients. Those with CNS involvement in the ICU often exhibited elevated blood urea nitrogen, creatinine, and creatine kinase levels. Higher mortality from COVID-19 was observed in ICU patients (P<0.0001). Conclusions: Multiple serum biomarkers, comorbidities, and neurological manifestations in COVID-19 patients have been consistently documented and may be linked to increased morbidity, ICU admission, and mortality. Recognizing and addressing these clinical and laboratory markers is essential for effective COVID-19 management.

COVID-19 in the intensive care unit: Unmasking the critical factors impacting patient survival.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, intensive care units (ICUs) around the world have been pushed to their limits as they grapple with the effects of the severe acute respiratory syndrome coronavirus 2 virus. Identifying prognostic factors that influence mortality in COVID-19 patients admitted to the ICU could offer valuable insights for clinicians seeking to prevent disease progression. A retrospective analysis was conducted on COVID-19 patients admitted to the ICU between January and September 2020. The analysis considered patient demographics, comorbidities, neurological and non-neurological symptoms, as well as laboratory markers. The multivariate logistic regression analysis aims to uncover associations between these factors and patient outcomes. Of the 387 patients included in this study, nearly half (48.5%) of the ICU patients succumbed to COVID-19. Factors that contributed to increased mortality included being 60 years of age or older, impaired consciousness, lung disease, elevated international normalized ratio (INR), and elevated blood urea nitrogen (BUN) levels. Surprisingly, symptoms such as dizziness/lightheadedness, myalgia, and headache were associated with a higher likelihood of survival. In addition, elevated D-dimer and aspartate aminotransferase (AST) levels, as well as lymphopenia, were more commonly observed in deceased patients. The study concluded that those who died in the ICU tended to be older, white, and burdened with more comorbidities and impaired consciousness. With the intriguing link between specific symptoms and survival, further research is essential to uncover the underlying pathophysiological mechanisms that influence ICU patient outcomes in the context of COVID-19.

Outcomes of Telestroke Inter-Hospital Transfers Among Intervention and Non-Intervention Patients.

Background: Telestroke is an established telemedicine method of delivering emergency stroke care. However, not all neurological patients utilizing telestroke service require emergency interventions or transfer to a comprehensive stroke center. To develop an understanding of the appropriateness of inter-hospital neurological transfers utilizing the telemedicine, our study aimed to assess the differences in outcomes of inter-hospital transfers utilizing the service in relation to the need for neurological interventions. Methods: The pragmatic, retrospective analysis included 181 consecutive patients, who were emergently transferred from telestroke-affiliated regional medical centers between October 3, 2021, and May 3, 2022. In this exploratory study investigating the outcomes of telestroke-referred patients, patients receiving interventions were compared to those that did not following transfer to our tertiary center. Neurological interventions included mechanical thrombectomy (MT) and/or tissue plasminogen activator (tPA), craniectomy, electroencephalography (EEG), or external ventricular drain (EVD). Transfer mortality rate, discharge functional status defined by modified Rankin scale (mRS), neurological status defined by National Institutes of Health Stroke Scale (NIHSS), 30-day unpreventable readmission rate, 90-day clinical major adverse cardiovascular events (MACE), and 90-day mRS, and NIHSS were studied. We used χ2 or Fisher exact tests to evaluate the association between the intervention and categorical or dichotomous variables. Continuous or ordinal measures were compared using Wilcoxon rank-sum tests. All tests of statistical significance were considered to be significant at P < 0.05. Results: Among the 181 transferred patients, 114 (63%) received neuro-intervention and 67 (37%) did not. The death rate during the index admission was not statistically significant between the intervention and non-intervention groups (P = 0.196). The discharge NIHSS and mRS were worse in the intervention compared to the non-intervention (P < 0.05 each, respectively). The 90-day mortality and cardiovascular event rates were similar between intervention and non-intervention groups (P > 0.05 each, respectively). The 30-day readmission rates were also similar between the two groups (14% intervention vs. 13.4% non-intervention, P = 0.910). The 90-day mRS were not significantly different between intervention and non-intervention groups (median 3 (IQR: 1 - 6) vs. 2 (IQR: 0 - 6), P = 0.109). However, 90-day NIHSS was worse in the intervention compared to non-intervention group (median 2 (IQR: 0 - 11) vs. 0 (IQR: 0 - 3), P = 0.004). Conclusions: Telestroke is a valuable resource that expedites emergent neurological care via referral to a stroke center. However, not all transferred patients benefit from the transfer process. Future multicenter studies are warranted to study the effects or appropriateness of telestroke networks, and to better understand the patient characteristics, resources allocation, and transferring institutions to improve telestroke care.

Experience with telemedicine in neuromuscular clinic during COVID-19 pandemic.

Objectives: The aim of the present study was to evaluate the feasibility and acceptability of telehealth for the care of neuromuscular patients during the COVID-19 pandemic. Methods: Neuromuscular patients or their caregivers, as well as health care providers (HCPs), who completed a televisit during the pandemic received an online survey, assessing satisfaction with the visit, quality of care, and experience with the televisit interference. Results: Surveys from 46 neuromuscular patients (including 18 with motor neuron disease [MND])/caregivers and 7 HCPs were completed. Several aspects of televisits including good communication, adequate time to discuss concern, provision of equal care, and telemedicine interference were rated favorably among participants. Telehealth was strongly satisfactory in 30 (65.22%) and satisfactory in 15 (32.61%) neuromuscular patients/caregivers. In 18 MND patients, this was 10 (55.56%) and 7 (38.89%), respectively. Moreover, 24 (52.17%) neuromuscular patients/caregivers would strongly agree and 18 (39.13%) would agree to participate again in televisits. This was 10 (55.56%) and 4 (33.33%) for MND cases, respectively. Various medical issues were addressed during the televisits including medication management, ordering tests/referrals, discussion of goals of care, and research. The predictive stepwise logistic model found younger age as a predicting factor for higher satisfaction from, or participation again in, televisits in neuromuscular patients. Limb onset location was also a predicting factor for strong satisfaction from televisits in MND cases. Conclusions: Telemedicine is feasible and highly effective at achieving personalized care that was rated satisfactory by the majority of neuromuscular patients/caregivers and HCPs during the COVID-19 pandemic.

Orexin receptor antagonists in the pathophysiology and treatment of sleep disorders and epilepsy.

The correlation between sleep and epilepsy has been argued over the past decades among scientists. Although the similarities and contrasts between sleep and epilepsy had been considered, their intertwined nature was not revealed until the nineteenth century. Sleep is recognized as a recurring state of mind and body through alternating brain electrical activities. It is documented that sleep disorders are associated with epilepsy. The origin, suppression, and spread of seizures are affected by sleep. As such, in patients with epilepsy, sleep disorders are a frequent comorbidity. Meanwhile, orexin, a wake-promoting neuropeptide, provides a bidirectional effect on both sleep and epilepsy. Orexin and its cognate receptors, orexin receptor type 1 (OX1R) and type 2 (OX2R), orchestrate their effects by activating various downstream signaling pathways. Although orexin was considered a therapeutic target in insomnia shortly after its discovery, its potential usefulness for psychiatric disorders and epileptic seizures has been suggested in the pre-clinical studies. This review aimed to discuss whether the relationship between sleep, epilepsy, and orexin is clearly reciprocal.

Predictors of Persistent Post-Surgical Pain Following Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management. METHODS: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus, and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by >1 study. RESULTS: Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% confidence interval [CI] 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score. CONCLUSIONS: Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery.

Targeting NMDA Receptor Complex in Management of Epilepsy.

N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the central nervous system (CNS) and play critical roles in neuronal excitability in the CNS. Both clinical and preclinical studies have revealed that the abnormal expression or function of these receptors can underlie the pathophysiology of seizure disorders and epilepsy. Accordingly, NMDAR modulators have been shown to exert anticonvulsive effects in various preclinical models of seizures, as well as in patients with epilepsy. In this review, we provide an update on the pathologic role of NMDARs in epilepsy and an overview of the NMDAR antagonists that have been evaluated as anticonvulsive agents in clinical studies, as well as in preclinical seizure models.

Impact of COVID-19 on Neuropsychiatric Disorders.

Since the Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many studies have shown that besides common COVID-19 symptoms, patients may develop various neuropsychiatric conditions including anxiety, mood disorders, psychosis, neurodegenerative diseases (e.g., dementia), insomnia, and even substance abuse disorders. COVID-19 can also worsen the patients underlying neuropsychiatric and neurodevelopmental conditions during or after the system phase of disease. In this review, we discuss the impact of SARS-CoV-2 infection on development or status of neuropsychiatric conditions during or following COVID-19.

Neuroprotective effects of Lasmiditan and Sumatriptan in an experimental model of post-stroke seizure in mice: Higher effects with concurrent opioid receptors or KATP channels inhibitors.

BACKGROUND: Early post-stroke seizure frequently occurs in stroke survivors within the first few days and is associated with poor functional outcomes. Therefore, efficient treatments of such complications with less adverse effects are pivotal. In this study, we investigated the possible beneficial effects of lasmiditan and sumatriptan against post-stroke seizures in mice and explored underlying mechanisms in their effects. METHODS: Stroke was induced by double ligation of the right common carotid artery in mice. Immediately after the ligation, lasmiditan (0.1 mg/kg, intraperitoneally [i.p.]) or sumatriptan (0.03 mg/kg, i.p.) were administered. Twenty-four hours after the stroke induction, seizure susceptibility was evaluated using the pentylenetetrazole (PTZ)-induced clonic seizure model. In separate experiments, naltrexone (a non-specific opioid receptor antagonist) and glibenclamide (a KATP channel blocker) were administered 15 min before lasmiditan or sumatriptan injection. To evaluate the underlying signaling pathways, ELISA analysis of inflammatory cytokines (TNF-α and IL-1ß) and western blot analysis of anti- and pro-apoptotic markers (Bcl-2 and Bax) were performed on mice isolated brain tissues. RESULTS: Lasmiditan (0.1 mg/kg, i.p.) and sumatriptan (0.03 mg/kg, i.p.) remarkably decreased seizure susceptibility in stroke animals by reducing inflammatory cytokines and neuronal apoptosis. Concurrent administration of naltrexone (10 mg/kg, i.p.) or glibenclamide (0.3 mg/kg, i.p.) with lasmiditan or sumatriptan resulted in a higher neuroprotection against clonic seizures and efficiently reduced the inflammatory and apoptotic markers. CONCLUSION: Lasmiditan and sumatriptan significantly increased post-stroke seizure thresholds in mice by suppressing inflammatory cytokines and neuronal apoptosis. Lasmiditan and sumatriptan seem to exert higher effects on seizure threshold with concurrent administration of the opioid receptors or KATP channels modulators.

Gene Therapy in Amyotrophic Lateral Sclerosis.

Since the discovery of Cu/Zn superoxide dismutase (SOD1) gene mutation, in 1993, as the first genetic abnormality in amyotrophic lateral sclerosis (ALS), over 50 genes have been identified as either cause or modifier in ALS and ALS/frontotemporal dementia (FTD) spectrum disease. Mutations in C9orf72, SOD1, TAR DNA binding protein 43 (TARDBP), and fused in sarcoma (FUS) genes are the four most common ones. During the last three decades, tremendous effort has been made worldwide to reveal biological pathways underlying the pathogenesis of these gene mutations in ALS/FTD. Accordingly, targeting etiologic genes (i.e., gene therapies) to suppress their toxic effects have been investigated widely. It includes four major strategies: (i) removal or inhibition of abnormal transcribed RNA using microRNA or antisense oligonucleotides (ASOs), (ii) degradation of abnormal mRNA using RNA interference (RNAi), (iii) decrease or inhibition of mutant proteins (e.g., using antibodies against misfolded proteins), and (iv) DNA genome editing with methods such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas). The promising results of these studies have led to the application of some of these strategies into ALS clinical trials, especially for C9orf72 and SOD1. In this paper, we will overview advances in gene therapy in ALS/FTD, focusing on C9orf72, SOD1, TARDBP, and FUS genes.

Modafinil exerts anticonvulsive effects against lithium-pilocarpine-induced status epilepticus in rats: A role for tumor necrosis factor-α and nitric oxide signaling.

BACKGROUND: Status epilepticus (SE) is a continuous episode of seizures which leads to hippocampal neurodegeneration, severe systemic inflammation, and extreme damage to the brain. Modafinil, a psychostimulant and wake-promoting agent, has exerted neuroprotective and anti-inflammatory effects in previous preclinical studies. The aim of this study was to assess effects of modafinil on the lithium-pilocarpine-induced SE rat model and to explore possible involvement of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) pathways in this regard. METHODS: Status epilepticus was provoked by injection of lithium chloride (127 mg/kg, intraperitoneally [i.p]) and pilocarpine (60 mg/kg, i.p.) in rats. Animals received different modafinil doses (50, 75, 100, and 150 mg/kg, i.p.) and SE scores were documented over 3 hours of duration. Moreover, the role of the nitrergic pathway in the effects of modafinil was evaluated by injection of the non-selective NO synthase (NOS) inhibitor L-NG-Nitro arginine methyl ester (L-NAME, 10 mg/kg, i.p.), the selective neuronal NOS inhibitor 7-nitroindazole (30 mg/kg, i.p.), and the selective inducible NOS inhibitor aminoguanidine (100 mg/kg, i.p.) 15 min before saline/vehicle or modafinil. The ELISA method was used to quantify TNF-α and NO metabolite levels in the isolated hippocampus. RESULTS: Modafinil at 100 mg/kg significantly decreased SE scores (P < 0.01). Pre-treatment with L-NAME, 7-nitroindazole, and aminoguanidine significantly reversed the anticonvulsive effects of modafinil. Status epilepticus-induced animals showed significantly higher NO metabolite and TNF-α levels in their hippocampal tissues, an effect that was reversed by modafinil (100 mg/kg, i.p.) treatment. Administration of NOS inhibitors resulted in excessive NO level reduction but an escalation of TNF-α level in modafinil-treated SE-animals. CONCLUSION: Our study revealed anticonvulsive effects of modafinil in the lithium-pilocarpine-induced SE rat model via possible involvement of TNF-α and nitrergic pathways.

Neurosyphilis presenting with focal middle cerebral artery stenosis and acute ischemic stroke: A case report.

Despite widespread screening and active management of syphilis infection, the rate of secondary and tertiary syphilis has increased over the past decade in the United States, especially with human immunodeficiency virus co-infection. We report a case of ischemic strokes in the middle cerebral artery (MCA) territory with focal stenosis of the left M1 segment of the MCA resulting from neurosyphilis with manifestation of subacute intermittent right-sided hemi-body numbness and transient word finding difficulties in a young adult with no prior known history of syphilis or significant cerebrovascular risk factors. A diagnostic cerebral angiogram was done which was initially concerning for possibility of reversible cerebral vasoconstriction syndrome (RCVS). The serum Treponema pallidum RPR testing resulted positive (1:32 titer) as well as subsequent reactive cerebrospinal fluid (CSF) VDRL test (ratio, 1:8). The patient was treated with intravenous ceftriaxone as well as verapamil and recovered without any residual deficits. To the best of our knowledge, this is the first reported evidence of possible RCVS in a case of neurosyphilis and related ischemic stroke. This case underscores the importance of evaluation for syphilis in young patients with fewer known vascular risk factors, who present with an ischemic stroke. Given the higher rates of stroke recurrence in neurosyphilis relative to few other stroke risk factors, early diagnosis, and treatment is furthermore essential to prevent disease progression.

Outcome Measures in Facioscapulohumeral Muscular Dystrophy Clinical Trials.

Facioscapulohumeral muscular dystrophy (FSHD) is a debilitating muscular dystrophy with a variable age of onset, severity, and progression. While there is still no cure for this disease, progress towards FSHD therapies has accelerated since the underlying mechanism of epigenetic derepression of the double homeobox 4 (DUX4) gene leading to skeletal muscle toxicity was identified. This has facilitated the rapid development of novel therapies to target DUX4 expression and downstream dysregulation that cause muscle degeneration. These discoveries and pre-clinical translational studies have opened new avenues for therapies that await evaluation in clinical trials. As the field anticipates more FSHD trials, the need has grown for more reliable and quantifiable outcome measures of muscle function, both for early phase and phase II and III trials. Advanced tools that facilitate longitudinal clinical assessment will greatly improve the potential of trials to identify therapeutics that successfully ameliorate disease progression or permit muscle functional recovery. Here, we discuss current and emerging FSHD outcome measures and the challenges that investigators may experience in applying such measures to FSHD clinical trial design and implementation.

Lithium and Erectile Dysfunction: An Overview.

Lithium has been a mainstay of therapy for patients with bipolar disorders for several decades. However, it may exert a variety of adverse effects that can affect patients' compliance. Sexual and erectile dysfunction has been reported in several studies by patients who take lithium as monotherapy or combined with other psychotherapeutic agents. The exact mechanisms underlying such side effects of lithium are not completely understood. It seems that both central and peripheral mechanisms are involved in the lithium-related sexual dysfunction. Here, we had an overview of the epidemiology of lithium-related sexual and erectile dysfunction in previous clinical studies as well as possible pathologic pathways that could be involved in this adverse effect of lithium based on the previous preclinical studies. Understanding such mechanisms could potentially open a new avenue for therapies that can overcome lithium-related sexual dysfunction and improve patients' adherence to the medication intake.