Central Nervous Disorders Research Articles

Navigating the Mysteries of CLIPPERS Syndrome: A Case Report of Long-Term Follow-Up.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a rare central nervous system inflammatory disorder with an unknown pathophysiology. We present the case of a 51-year-old female exhibiting clinical and radiological features consistent with CLIPPERS syndrome. She manifested diplopia, vertigo, gait ataxia, and lower limb asthenia, accompanied by impaired tandem gait, right sixth nerve palsy, and coarse horizontal nystagmus during the physical examination. Magnetic resonance imaging (MRI) revealed punctate and curvilinear lesions centered in the pons. Treatment with glucocorticoids resulted in significant clinical improvement, and the patient was discharged with a maintenance dose of prednisolone. Throughout a four-year follow-up period, the patient remained symptom-free without any relapses using the low-dose corticosteroid. The CLIPPERS syndrome diagnosis remains challenging, but recent evidence supports an autoimmune pathogenesis. Although corticosteroid treatment has shown significant clinical improvement, there are no established guidelines or clinical trials on the optimal therapeutic regimen. Despite its rarity, clinicians should consider CLIPPERS syndrome in patients with compatible clinical and radiological features to prevent irreversible neurological damage.

Prolonged Visual Evoked Potential Latencies in Dogs Naturally Infected with Canine Distemper Virus

Canine distemper (CD) is a deadly, multi-system infection caused by a Morbillivirus. The canine distemper virus (CDV) frequently affects the nervous system with demyelinating leukoencephalitis, the most common neurological lesion. The disease has been linked to multiple sclerosis (MS) in humans due to similar clinical presentation and pathophysiological mechanisms. In MS, visual evoked potentials (VEPs) have been identified as a reliable marker for disease progression, enabling the early detection of clinically suspected lesions. The aim of this study was to determine if there are any abnormalities in VEP responses in dogs with neurological CD. Visual evoked potentials and electroretinogram (ERG) were recorded at both the cranial and spinal levels in dogs naturally infected with CDV and in healthy dogs. The results in the CDV-infected group revealed a bilateral increase in the latency of N1, P1, N2, P2, and N3 waves of the VEPs, without any alterations in their amplitudes. No significant differences were observed in the ERG between the groups. These results suggest that altered VEP responses could serve as an early diagnostic indicator of neurological damage caused by distemper. Therefore, conducting these studies could potentially aid in the detection of central nervous conduction disorders during the subclinical phases of the disease.

Hippocampal SENP3 mediates chronic stress-induced depression-like behaviors by impairing the CREB-BDNF signaling.

Impaired signaling between cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus is generally considered to be the cause of depression. The mechanisms underlying the impairment of CREB-BDNF signaling under stress conditions are largely unclear. Small ubiquitin-like modifier (SUMO) specific peptidase 3 (SENP3) is a molecule that can regulate SUMOylation of target proteins related to synaptic plasticity. Its dynamic changes have been reported to be associated with neuronal damage in various models of central nervous disorders such as cerebral ischemia and traumatic brain injury. However, its role in depression is completely unknown. This problem was addressed in the present study. Our results showed that chronic unpredictable stress (CUS) triggered a specific increase in SENP3 expression in the hippocampus of non-stressed mice. Overexpression of SENP3 in the hippocampus of non-stressed mice elicited depression-like behaviors in the tail suspension test, forced swimming test, and sucrose preference test, accompanied by impairment of the CREB-BDNF signaling cascade in the hippocampus. Conversely, genetic silencing of SENP3 in the hippocampus suppressed the development of depression-like behaviors. Furthermore, infusion of SENP3-shRNA into the hippocampus failed to suppress CUS-induced depression-like behaviors when mice received genetic silencing CREB or BDNF in the hippocampus or inhibition of the BDNF receptor by K252a. Taken together, these results suggest that abnormally elevated SENP3 in the hippocampus leads to the development of depression-like behavior by impairing the CREB-BDNF signaling cascade. SENP3 in the hippocampus could be a promising target for the development of new antidepressants.

Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.

Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.

The bidirectional role of music effect in epilepsy: Friend or foe?

Epilepsy is a prevalent neurological disease that impacts around 70 million individuals globally. Anti-seizure medications (ASMs) are the first choice for clinicians to control unprovoked epileptic seizures. Although more than 30 ASMs are available in the market, patients with epilepsy (PWEs) still show poor responses to adequate drug treatment. Meanwhile, long-term medications not only bring heavy financial burdens but also lead to undesirable side effects. Music, a ubiquitous art form throughout human history, has been confirmed as therapeutically effective in various neurological conditions, including epilepsy. This alternative therapy offers convenience and a relatively safe approach to alleviating epileptic symptoms. Paradoxically, besides anti-convulsant effect, some particular music would cause seizures inversely, indicating the pro-convulsant effect of it. Considering that investigating the impact of music on epilepsy emerges as a compelling subject. In this review, we tried to present the following sections of content on this topic. Initially, we overviewed the impact of music on the brain and the significant progress of music therapy in central neurological disorders. Afterward, we classified the anti-convulsant and pro-convulsant effects of music in epilepsy, relying on both clinical and laboratory evidences. Finally, possible mechanisms and neural basis of the music effect were concluded, and the translational potentials and some future outlooks about the music effect in epilepsy were proposed. PLAIN LANGUAGE SUMMARY: Epilepsy is an extremely severe neurological disorder. Although anti-seizure medications are preferred choice to control seizures, the efficacy is not satisfied due to the tolerance. Anecdotal music effect had been deemed functional diversity but not clarified on epilepsy, pro-convulsive, or anti-convulsive. Here, we reviewed this interesting but puzzling topic, as well as illustrating the potential mechanisms and its translational potential.

The impact of hypertensive disorders during pregnancy on maternal and fetal outcomes: A retrospective study in South Asian region of Pakistan

The current study was conducted to check the effect of high blood pressure on the health of mother and child living in south Asian region of Pakistan during all trimesters of pregnancy. For this retrospective research, 720 females during their deliveries were analyzed at Swat Medical College and Women's Hospital Mardan between June 2022 and June 2023. This current study found almost one fourth of the population suffer hypertensive disorders during any stage of pregnancy which leads to mild to severe pre-eclampsia and ultimately premature births. The observations indicated statistically high significance between hypertensive disorders and associated adverse symptoms like fetus with preterm delivery, c-sections, low birth weight, acute to chronic but reversible renal disorders, neonatal intensive care admissions and sometime central nervous system related disorders. So, this study concludes that more comprehensive parenteral care at the time of pregnancy and especially at the last trimesters. Keen attention towards symptoms and early diagnosis can help to reduce the severity of disease. The maternal and fetal health initiative schemes are required for public awareness.

Neuroinflammatory Disorders of the Central Nervous System Associated with Monkeypox Virus Infection: A Systematic Review and Call to Action.

The Monkeypox virus, a zoonotic pathogen of the Orthopoxvirus genus, has shown a marked global spread, resulting in cases of neuroinflammatory disorders. This systematic review aims to summarize the central nervous system manifestations linked to monkeypox virus infection. We conducted a systematic review according to PRISMA guidelines. Databases such as PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to September 2024. Inclusion criteria focused on monkeypox virus-positive patients with confirmed central nervous system inflammatory disorders, including encephalitis, meningitis, myelitis, and related neuroimmune diseases. From 770 screened articles, 38 studies were included. Of the 20 reported monkeypox virus-infected cases with central nervous system involvement, the most common manifestations were encephalitis (40%), encephalomyelitis (30%), and meningoencephalitis (10%). Additional rarer presentations included Guillain-Barré syndrome (5%) and transverse myelitis (5%). The mean age of affected individuals was 27.9±13.69 years, and 75% were male. Fever, fatigue, and myalgia were the predominant systemic symptoms, with neurological complications often appearing within 4.6±2.5 days post-infection. Diagnoses were confirmed by quantitative reverse transcription polymerase chain reaction, magnetic resonance imaging, and cerebrospinal fluid analysis. Treatment strategies varied, with antivirals (e.g., tecovirimat) and immunomodulatory therapies (e.g., methylprednisolone, immunoglobulins, and rituximab) utilized. Monkeypox virus infection is associated with severe neuroinflammatory disorders, with varying outcomes from complete recovery to mortality. Increased awareness, comprehensive diagnostic approaches, and targeted therapeutic interventions are critical in managing these cases. Further research is required to elucidate the mechanisms of neuroinflammation in the monkeypox virus and establish standardized treatment protocols.

Early Diagnosis of CNS Virus Infections from Neurological Autoimmune Diseases: A Cross-Sectional Study from China in ER Setting.

It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases.

Analysis of effectiveness of Fecal Microbiota Transplantation in Multiple Sclerosis

Multiple Sclerosis is a chronic, autoimmune disorder characterized by demyelination and neuroinflammation affecting 2.3 million people around the world. MS have different types, relapsing and remitting MS being the most prevalent type with unpredicted flare ups with complete or incomplete recovery of the patient. Research suggests the emerging impact of alterations in gut microbiome on various diseases. The dysbiosis of gut flora has been linked to various diseases one of many is central nervous system autoimmune disorders. The study aims to evaluate the potential role and effectiveness of FMT in treating MS. The literature and clinical trials focused on gut microbiota, efficacy, Safety, and mechanisms of FMT were analyzed. The major focus of the study is assessing the impact of FMT on MS symptoms and gut microbiota composition and results of the study were concluded based on outcomes. Primary outcomes noted improvement in MS symptoms both subjectively and objectively including enhanced motor symptoms and improved disability scores like EDSS. Secondary outcomes showed significant improvement in gut microbiota and 55-65% reduction in inflammatory markers like IL 6 and TNF alpha. FMT shows promising outcomes to be considered as a therapeutic intervention in MS by offering symptom relief and halting disease progression.

Cortical auditory evoked potentials in peripheral neuropathy

BackgroundCortical auditory evoked potentials (CAEPs) display both auditory processing and neurological activity in the auditory cortex. The purpose of this research is to evaluate the importance of CAEPs in identifying auditory processing disorders in patients with peripheral neuropathy (PN) in different pathologies. Sixty cases with PN of different pathologies represented the study group which was classified into two subgroups according to the underlying pathology of PN: those with either axonal PN (44 patients) and those with demyelinating PN (16 patients). The current study also included a control group of 40 healthy volunteers who did not have any peripheral or central auditory neurological disorders. CAEPs were recorded in both groups.ResultsThe study group’s CAEP response showed significantly delayed latencies than the control groups. Comparing the two study subgroups revealed that the axonal PN group had significant delayed latencies of N1 and P2 components in comparison to the demyelinating PN group.ConclusionCortical auditory evoked potentials can be used efficiently to diagnosis central auditory processing disorders in patients with PN. CAEP latencies can be employed alone or in conjunction with amplitudes; however, CAEP latencies are more significant than amplitudes for such purpose. Both demyelinating and axonal PN are associated with impaired auditory processing; however, axonal PN patients are more likely to be affected, suggesting that axonal PN has a significantly drastic effect on the central auditory nervous system.

Central Neurogenic Hyperventilation Following Ischemic Stroke in the Pons

Central neurogenic hyperventilation (CNH) is a rare condition that characterized by an increase in the rate and depth of respiration to an extent that produces advanced respiratory alkalosis due to various central nervous disorder. The mechanism of CNH remains unclear. We reported a case of CNH in patients with progressive ischemic stroke in pons, including parabrachial nucleus, which is thought to have disrupted inhibitory impulses to the medullary respiratory center.

Bloodstream infections among patients receiving therapeutic plasma exchanges in the intensive care unit: a 10 year multicentric study

BackgroundTherapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors.MethodsWe retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model.ResultsOver 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2–7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3–11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21–8.32]) and total number of TPE sessions (OR 1.14 [1.08–1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010).ConclusionBlood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions.

Switching from injectable to other Disease Modifying Therapies may improve sexual dysfunction in people with Multiple Sclerosis

BackgroundMultiple Sclerosis (MS) a central nervous system autoimmune disorder, mainly affecting young adults and more prevalent among women, can lead to sexual dysfunction (SD) among both males and females with MS. Female sexual dysfunction can be defined as dyspareunia, a lack of sexual desire, disorders in the arousal and orgasm phases, and sexual pain disorders. The purpose of this study is to investigate the changes in sexual function among females with MS whose treatment was switched from first-line injectable medications to other agents after a six-month duration. And assess the changes in all three domains of SD.MethodsIn this longitudinal study females diagnosed with MS, aged between 18 and 50 years old, and were candidates for switching their treatment from interferon beta-1a (intra-muscular and subcutaneous), and Glatiramer Acetate (GA), to Fingolimod, Dimethyl Fumarate (DMF), or Natalizumab (NTZ) due to patients’ convenience and tolerability and adverse events were included. “Multiple Sclerosis Intimacy and Sexuality Questionnaire-19” was used to evaluate the SD changes before and six months after the new treatment initiation. Statistical analysis was conducted using SPSS V.24 software. Histograms and the Shapiro-Wilk test were used to assess the normality of the variables; due to the non-normal distribution of quantitative variables (except for age), the Wilcoxon signed-rank test was used to compare the scores, before and six months after the medication change. The level of significance was considered less than 0.05.ResultsOut of 107 female participants (average age: 35.09 ± 5.61), The mean of overall MSISQ-19 scores, before and six months after the medication change were not significant (p-value = 0.091). However, considering the subdomains, the medication changes only affected the tertiary subdomain of MSISQ-19 (p-value = 0.017). Still, the scores of other subdomains did not change significantly (p-value = 0.761 for primary SD and 0.479 for secondary SD). Also, there wasn’t any significant difference between EDSS before and after the medication change (p-value = 0.461).ConclusionsTo our knowledge, this was the first study, assessing the effect of MS medication change on the improvement of SD among patients. According to the results of the presented cross-sectional study, we found that during a six-month period, the tertiary subdomain of MSISQ-19 symptoms improved significantly, while the changes in other SD domains were not significant.

Lymphocytic Choriomeningitis Virus Infections in Hungary between 2017-2023-Investigation of the First Congenital Infections.

Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent-borne arenavirus, primarily spread by common house mouse species. Acquired human infections range from asymptomatic to mild flu-like symptoms and self-resolving neurological diseases. In contrast, intrauterine LCMV infection is associated with high mortality and morbidity. Infection of the fetus often leads to fetal death, and surviving fetuses may develop vision impairment and central nervous system developmental disorders. LCMV is mainly diagnosed by serological methods using in-house indirect immunofluorescence assays. LCMV nucleic acid is detected by the nested RT-PCR method and confirmed by Sanger sequencing. In Hungary, 23 acquired lymphocytic choriomeningitis cases were diagnosed between 2017 and 2023. Ten out of 23 confirmed patients proved to be positive by the PCR method. Two cases of intrauterine LCMV infections were detected in 2019 and 2021, respectively. The IgG antibody titers measured in the infant's serum samples were much higher than the IgG titers of the maternal serum samples. Both IgM and IgA antibodies were detectable in the infants' sera. As the microbiological diagnosis of LCMV is rather challenging and the symptoms are very similar to the clinical picture of other common teratogenic pathogens such as cytomegalovirus or Toxoplasma gondii, intrauterine LCMV infections might still be underdiagnosed.

Quantitative ultrasound of submental and masticatory muscles in children with cerebral palsy.

Quantitative muscle ultrasound (QMUS) is potentially valuable as a diagnostic tool in central neurological disorders, as it provides information about changes in muscle architecture. This study aimed to investigate whether ultrasound images of the submental and masticatory muscles in children with spastic cerebral palsy (CP) differ from those obtained in a reference group, and whether observed ultrasound abnormalities differ between subgroups of children with different Eating and Drinking Ability Classification System (EDACS) levels to support its construct validity. A prospective cohort study was conducted in 25 children with spastic CP aged 3-18 years. QMUS of selected muscles was performed. Muscle thickness and echogenicity in the CP group were compared to previously collected reference values, and between different EDACS levels within the CP group. Median echogenicity of all muscles was significantly higher in children with CP than in healthy controls. The temporalis muscle was significantly thinner in the CP group. There were no differences in muscle thickness or echogenicity between EDACS levels. QMUS is able to detect abnormal architecture of submental and masticatory muscles in children with spastic CP, but the interpretation of abnormalities in relation to the severity of mastication and swallowing problems needs further investigation.

Translation and validation of the Persian version of “The Psychosocial Impact of Assistive Devices Scale” in patients with neurological disorders

ABSTRACT Neurological disorders are a heterogeneous group of central or peripheral nervous disorders of which the main symptoms include impaired walking and balance. One of the main interventions for neurological disorders is the use of assistive devices, and it is necessary to consider the psychosocial effects of these devices on users. The psychometric properties of the Persian version of the Psychosocial Impact of Assistive Devices Scale (PIADS) were evaluated in patients with neurological disorders. After translating the scale into Persian based on IQULA, face and content validity were determined. The divergent validity of the scale was examined through its relationship with the Orthotics and Prosthetics Users’ Survey (OPUS). Reliability of the tool was evaluated using an internal consistency and test-retest method over two weeks with 50 patients with neurological disorders and a history of using assistive devices for at least six months. The face and content validity of the PIADS was confirmed. The ICC for all subscales was higher than 0.78, which indicates a good correlation. However, the divergent validity of the scale with the OPUS scale was not confirmed. The Persian version of PIADS is a valid and reliable measure for patients with neurological disorders in Iran.

Turmeric Extract Bioindicator in Identification of Borax Compounds in Meatballs

Meatballs are food made from beef, chicken, fish and shrimp, which are popular with people, from children to adults. In managing meatballs, food additives (BTP) are often added which can make the meatballs chewier and last longer, thereby inhibiting the growth of microorganisms caused by the borax content. Borax is a substance that is often used as a preservative and improves the texture of foods such as meatballs, however the use of borax as a food preservative is prohibited in Indonesia because it can cause various diseases such as central nervous disorders and liver problems. This research is to determine whether or not there is Borax in Meatballs that are bought and sold around Praya City, Central Lombok Regency by using a sampling method from 5 meatball stalls, from samples that have been qualitatively tested, several samples have borax content which was tested using turmeric extract, showing that the color change in the meatball samples that had been dripped with turmeric extract contained 3 negative control meatball samples (-) A, C, D, and 2 positive controls (+) B and E, while the 2 positive (+) meatball samples were tested using borax FT-IR to detect OH groups (Hydroxyl) C=C bonds and C-H bonds are found in the Spectra.

Recurrent hyponatremia in neonate: a case of renal salt wasting syndrome

BackgroundRenal salt wasting (RSW) is primarily seen with central nervous disorders and is characterized by hyponatremia, elevated urinary sodium excretion, increased urine output, and hypovolemia. Although there have been reports of RSW in children, it has not been reported in newborns.Case presentationA term (38 weeks 2 days) female weighing 2060 g, born via normal vaginal delivery, to a primi-gravida mother, was admitted to our neonatal intensive care unit. At birth, the baby was non-vigorous, had aspirated meconium, and required bag-and-mask ventilation following which the baby cried. The child was put on CPAP and inotropes for respiratory distress and shock, respectively, along with first-line antibiotics. Over the next few days, the child was weaned off CPAP, inotropes were stopped, and feeds were started. On postnatal day (PND) 8, the baby developed repeated episodes of seizures requiring two-antiepileptics followed by midazolam infusion, had shock requiring inotropes, and also had a tense anterior fontanelle with altered sensorium and tone changes, for which mannitol and 3% saline were given. Antibiotics were upgraded, and neuroimaging (MRI) revealed left basal-ganglia bleed with intraventricular extension and cerebral venous thrombosis. The baby showed gradual clinical improvement with the above measures and was restarted on feeds. However, from PND-19 onwards the baby had repeated episodes of hyponatremia requiring 3% saline infusions, progressive weight loss, and polyuria. Considering RSW, urine sodium was done which was high (110 mmol/L). For polyuria and weight loss, feed volume was increased, whereas, for hyponatremia, table salt was added to the expressed breast milk (1 gm × tds). Subsequently, all the serum sodium values remained within normal limits, and the baby started gaining weight and was discharged on similar advice (PND 38). On further follow-up, table salt was gradually decreased in the feeds and was stopped after 1 month of discharge with normal serum sodium values.ConclusionManagement of recurrent hyponatremia in a neonate is challenging. Despite its rarity, RSW in newborns should be considered a differential.

A disease warranting attention from neurosurgeons: primary central nervous system post-transplant lymphoproliferative disorder.

Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents. From 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT). Four patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness (n = 4), headache (n = 2), confusion (n = 2), and nausea (n = 2), with ring-enhancing (n = 5), typically solitary (n = 3) and supratentorial (n = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy (n = 4) or craniotomy (n = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases (n = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab (n = 3), surgical resection (n = 2), zanubrutinib (n = 1), whole-brain radiation (n = 1), and methotrexate (n = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive. In patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.

In-depth Mechanism, Challenges, and Opportunities of Delivering Therapeutics in Brain Using Intranasal Route.

Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood-brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.