Hand knob sign in osmotic demyelinating syndrome.

BACKGROUND: Osmotic demyelinating syndrome, commonly recognized as a consequence of the rapid correction of hyponatremia, has been known to cause motor, neuropsychiatric, or extrapyramidal symptoms. We reported a patient with an unusual presentation involving bilateral hand weakness, and pseudobulbar affect. The imaging was compatible with osmotic demyelinating syndrome with bilateral hand knob lesions, despite no history of overcorrection of hyponatremia. CASE PRESENTATION: A 44-year-old female presented with three weeks of emotional lability, spastic dysarthria, and bilateral hand weakness following ankle surgery and a mild head injury. Physical examination revealed weakness in the intrinsic hand muscles, leading to a claw-like deformity of the hands, although sensation remained unimpaired. Magnetic resonance imaging (MRI) of the brain revealed several hyperintensities on fluid-attenuated inversion recovery imaging involving various areas, including the hand knob area of the bilateral precentral gyri, caudate, lentiform nuclei, and pons, suggestive of osmotic demyelinating syndrome. Clinical improvement was observed following a trial of intravenous pulse methylprednisolone and plasmapheresis. CONCLUSIONS: Bilateral hand weakness is an unusual manifestation of osmotic demyelinating syndrome. The precentral gyrus, specifically in the hand knob area, is the vulnerable region that can result from osmotic demyelinating syndrome.

COVID-19 related acute necrotizing encephalopathy with extremely high interleukin-6 and RANBP2 mutation in a patient with recently immunized inactivated virus vaccine and no pulmonary involvement.

BACKGROUND: We report the first case of COVID-19 associated acute necrotizing encephalopathy (ANE) without pulmonary disease in a patient with an extremely high interleukin-6 (IL-6) level and Ran Binding Protein 2 (RANBP2) mutation. CASE PRESENTATION: A 29-year-old woman recently immunized with inactivated viral vaccine-BBIBP32-CorV (Sinopharm) presented with alteration of consciousness. Her body temperature was 37° Celsius, blood pressure 42/31 mmHg, heart rate 130 bpm, respiratory rate 20 per minute, and oxygen saturation 98%. Respiratory examination was unremarkable. Neurological examination revealed stupor but preserved brainstem reflexes. Non-contrast computerized tomography of the brain showed symmetrical hypodense lesions involving bilateral thalami and cerebellar hemispheres characteristic of ANE. No pulmonary infiltration was found on chest radiograph. SARS-CoV-2 was detected by PCR; whole genome sequencing later confirmed the Delta variant. RANBP2 gene analysis revealed heterozygous Thr585Met mutation. Serum IL-6 was 7390 pg/mL. Urine examination showed pyelonephritis. Her clinical course was complicated by seizure, septic shock, acute kidney injury, and acute hepatic failure. She later developed coma and passed away in 6 days. CONCLUSIONS: ANE is caused by cytokine storm leading to necrosis and hemorrhage of the brain. IL-6 was deemed as a prognostic factor and a potential treatment target of ANE in previous studies. RANBP2 missense mutation strongly predisposes this condition by affecting mitochondrial function, viral entry, cytokine signaling, immune response, and blood-brain barrier maintenance. Also, inactivated vaccine has been reported to precipitate massive production of cytokines by antibody dependent enhancement (ADE). The true incidence of COVID-19 associated ANE is not known as were the predictors of its development. We proposed these potential two factors (RANBP2 mutation and ADE) that could participate in the pathogenesis of ANE in COVID-19 apart from SARS-CoV2 infection by itself. Further study is needed to confirm this hypothesis, specifically in the post-vaccination period. Role of RANBP2 mutation and its application in COVID-19 and ANE should be further elaborated.

Evaluating the efficiency of specimen pooling for PCR-based detection of COVID-19.

In the age of a pandemic, such as the ongoing one caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to evaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time polymerase chain reaction (PCR), were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct > 35), 2 of 15 pools (13.3%) were false negative. Pooling specimens to test for Coronavirus Disease 2019 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower-risk populations.

Spike S2 Subunit: Possible Target for Detecting Novel SARS-CoV-2 Variants with Multiple Mutations.

Novel SARS-CoV-2 variants have multiple mutations that may impact molecular diagnostics. The markedly conserved S2 subunit may be utilized to detect new variants. A comparison of 694 specimens (2019-2022) in Thailand using a commercial RT-PCR kit and the kit in combination with S2 primers and a probe was performed. Delayed amplification in ORF1ab was detected in one BA.4 omicron, whereas no amplification problem was encountered in the S2 target. There were no statistically significant differences in mean Ct value between the target genes (E, N, ORF1ab, and S2) and no significant differences in mean Ct value between the reagents. Furthermore, 230,821 nucleotide sequences submitted by 20 representative counties in each region (Jan-Oct 2022) have been checked for mutations in S2 primers and probe using PrimerChecker; there is a very low chance of encountering performance problems. The S2 primers and probe are still bound to the top five currently circulating variants in all countries and Thailand without mismatch recognition (Jun-Nov 2023). This study shows the possible benefits of detecting S2 in combination with simultaneously detecting three genes in a kit without affecting the Ct value of each target. The S2 subunit may be a promising target for the detection of SARS-CoV-2 variants with multiple mutations.

Fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome: a case report.

BACKGROUND: Fluorouracil-induced leukoencephalopathy is a rare complication and has been reported to present as confusion, oculomotor abnormality, ataxia, and parkinsonism; however, there is no previous report of a presentation mimicking neuroleptic malignant syndrome. Acute cerebellar syndrome may occur, which can be explained by the extremely high accumulation of the drug in the cerebellum. However, presentation mimicking neuroleptic malignant syndrome similar to our case has never been reported. CASE PRESENTATION: Here, we describe a 68-year-old Thai male presenting with advanced-stage cecal adenocarcinoma, as well as symptoms and signs indicative of neuroleptic malignant syndrome. He received two doses of intravenous metoclopramide 10 mg 6 hours before his symptoms occurred. Magnetic resonance imaging scan revealed signal hyperintensity within the bilateral white matter. Further evaluation showed that his thiamine level was extremely low. Thus, he was diagnosed with fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome. The concomitant fluorouracil-induced thiamine deficiency eventually leads to rapid depletion of thiamine and was considered a risk factor for fluorouracil-induced leukoencephalopathy. CONCLUSION: Fluorouracil-induced leukoencephalopathy is believed to be caused by insult causing mitochondrial dysfunction. However, the exact mechanism remains unknown, but our finding suggests that thiamine deficiency plays a crucial role in fluorouracil-induced leukoencephalopathy. Diagnosis is usually delayed due to a lack of clinical suspicion and results in significant morbidity requiring unnecessary investigations.

Unusual thalamic mass and subsequent gelatinous pseudocysts in an immunocompetent host: A case report.

Cryptococcal meningoencephalitis often occurs in an immunocompromised host with several known neurological manifestations including space-occupying lesions, meningitis or meningoencephalitis. Here, we describe a 38-year-old previously healthy durian farm owner with cryptococcoma and subsequent development of cryptococcus gelatinous pseudocyst after receiving high doses of intravenous dexamethasone to treat mass lesion presumed to be a malignant process. An MRI scan of the head demonstrated a 2-cm heterogeneous solitary enhancing cystic lesion at the right thalamus. Progression of neurological deficit and another repeat imaging showing typical appearance of gelatinous pseudocyst. Lumbar puncture found markedly elevated pressure and cryptococcal antigen strongly positive confirming the diagnosis. He was immediately started on amphotericin B and flucytosine for cryptococcus meningoencephalitis with partial improvement in his vision. This report highlights consideration of cryptococcal infection in an immunocompetent host to avoid delays in diagnosis and treatment.

Elevation of plasma phosphorylated tau181 during neurological illnesses affecting consciousness and kidney dysfunction.

Introduction: Phosphorylated tau (p-tau)181 has become a promising blood-based Alzheimer's disease (AD) biomarker. We studied the agreement of plasma p-tau181 and cerebrospinal fluid (CSF) markers in patients with alteration of consciousness (AOC). Methods: Plasma and CSF were simultaneously collected in participants presenting with AOC. Plasma p-tau181 was measured using the single-molecule array. CSF biomarkers were classified according to the amyloid/tau/neurodegeneration (AT[N]) framework. Results: Among participants enrolled, the median (interquartile range) age was 57 (28.5-75) years and 5.8% had AD. Plasma p-tau181 yielded area under the curve of 0.85 and showed moderate correlation with CSF p-tau181 (Rho = 0.42, P < .001). Using the historical cut-point, many non-AD participants had elevated plasma p-tau181 resulting in a specificity of 0.57. Plasma p-tau181 correlated with the glomerular filtration rate (Rho = -0.52, P < .001). Among A- participants with elevated plasma p-tau181, 42% had kidney dysfunction. Discussion: Plasma p-tau181 showed inadequate specificity in patients with AOC partially attributable to concomitant kidney dysfunction.

IP-10 and complement activation as friend or foe in COVID-19.

INTRODUCTION: The Innate immune system senses danger signals of COVID-19 infection and produce an orchestration of cellular, complement and cytokines cascades. These led to the approach using immunosuppressive agents. It is intriguing whether certain biomarkers can aid the proper administration of such drugs. METHODS: Plasma specimens of 58 COVID-19 patients with differing severity, from very mild illness (group A), mild (group B), moderate (group C), and severe/critical illness (group D) were assayed for cyto-chemokines and terminal complement complex (SC5b-9) during the course of diseases. None received anti-IL-6 therapy, there was no mortality in this cohort. RESULTS: IP-10 and RANTES levels were dominant cytokines. IP-10 levels increased significantly in all groups when compared between pre-nadir and nadir phases (group A, p =0.428; group B =0.034; group C =0.159; group D <0.001) and in groups B and D when compared between nadir and recovery phases (p <0.001). RANTES levels were elevated in all groups across all phases with no significant differences. SC5b-9 levels increased significantly as compared to healthy controls [pre-nadir- group A versus healthy, p =0.122; group B-D versus healthy, p =0.021); nadir-group A versus healthy, p =0.003; group B-D versus healthy, p <0.001; recovery phase (p <0.001)] but not between groups A and B-D at pre-nadir (p=0.606). CONCLUSION: The absence of significant pro-inflammatory responses and early elevation of IP-10 levels and complement activation may be favorable and necessary for viral elimination in COVID-19 patients. Expression of distinct cyto-chemokines during each clinical phase may be useful for guiding proper therapeutic interventions on alleviating thrombo-inflammation responses to COVID-19 infection.

A case of successive development of possible acute necrotizing encephalopathy after COVID-19 pneumonia.

COVID-19 infection often results in an excessive inflammatory response with a spectrum of neurological manifestations. Here, we describe an 81-year-old female with severe COVID-19 pneumonia and subsequent alteration of consciousness after high-dose intravenous dexamethasone and remdesivir. A non-contrast head computed tomography (CT) demonstrated bilateral hypodensities involving bilateral cerebellar hemispheres, thalami, cerebral peduncles and medial parieto-occipital areas. There was no improvement and repeat CT showed progression with findings suggestive of acute necrotizing encephalopathy. Interleukin-6 levels were initially normal; however, subsequent levels were found to be markedly elevated. Acute necrotizing encephalopathy associated with COVID-19 may occur in the setting of severe pneumonia and may represent an immune-mediated process involving inflammatory cytokines such as interleukin-6.

Rabies: Presentation, case management and therapy.

Several Lyssaviruses are known to be a causative agent of rabies and rabies like syndrome. There are no proven effective treatment strategies for symptomatic rabies patient. Risk of infection from dog variant of rabies virus is highest with deep bite reaching muscular layer and much higher when compared to scratch. Failure of viral eradication at the central nervous system (CNS) is partly due to inadequate immune response. Favipiravir selectively inhibit viral RNA polymerase and has been shown to reduce rabies replication in neuronal cell and mouse model system. Endocannabinoid system has emerged as an important regulator for CNS integrity, cell fate and may serve as an important novel neuroprotective agent. Cannabinoid may be able to regulate the impaired homeostasis induced by rabies virus by promoting infected cell survival and promote complete autophagy in infected cell.

Encephalitis in Thailand: A Neglected Disease Increasingly Caused by Enterovirus.

From 2013 to 2018, the Thai Red Cross Emerging Infectious Disease-Health Science Center (TRC-EID-HS), in collaboration with the Department of Disease Control (DDC) and the Ministry of Public Health (MOPH) Thailand, conducted encephalitis surveillance. A total of 1700 cerebrospinal fluid (CSF) samples from patients with encephalitis were tested by a predesigned multiplex PCR. Diagnosis was made in 318 cases (18.7%), 86 (27%) of which were caused by Epstein-Barr virus (EBV), 55 (17.3%) by enteroviruses (EV), 36 (11.3%) by varicella-zoster virus (VZV), 31 (9.7%) by cytomegalovirus (CMV), 25 (7.8%) by herpes simplex virus type 1 (HSV-1), and 20 (6.3%) by human herpesvirus 6 (HHV-6). Results were compared with 3099 CSF samples from patients with encephalitis collected between 2002 to 2012, which were tested by specific PCR assays. Diagnosis was made in 337 (10.9%) of these cases, and 91 (27%) were CMV, 79 (23.4%) were VZV, 72 (21.4%) were EBV, 39 (11.6%) were EVs, 39 (11.6%) were HSV-1, 33 (9.8%) were HSV-2, and 2 (0.6%) were Dengue virus (DENV). The change in the pattern toward EVs as a major cause of viral encephalitis was unexpected, and a change in viral neurotropism may be responsible.

Detection of influenza virus in rectal swabs of patients admitted in hospital for febrile illnesses in Thailand.

INTRODUCTION: Influenza virus favours the respiratory tract as its primary site of host entry and replication, and it is transmitted mainly via respiratory secretions. Nasopharyngeal swab is the gold standard specimen type for influenza detection, but several studies have also suggested that the virus replicates in the human gastrointestinal tract. METHODS: A retrospective study was conducted on all patients positive for influenza virus and initially recruited as part of the PREDICT project from 2017 to 2018. The objectives of the study were to investigate whether rectal swab could aid in improving influenza detection, and if there was any correlation between gastrointestinal disturbances and severity of infection, using length of hospital stay as an indicator of severity. RESULTS: Of the 51 influenza-positive patients, 12 had detectable influenza virus in their rectal swab. Among these 12 rectal swab positive patients, influenza virus was not detected in the nasopharyngeal swab of three of them. Gastrointestinal symptoms were observed for 28.2% patients with a negative rectal swab negative and 25.0% patients with a positive rectal swab. Average length of hospital stay was 4.2 days for rectal swab positive group and 3.7 days for rectal swab negative group. This difference was not statistically significant (p = 0.288). CONCLUSIONS: There is no correlation between influenza virus detection in rectal swab and gastrointestinal disturbances or disease severity, and there is currently insufficient evidence to support replicative ability in the gastrointestinal tract.

Low-cost management of mushroom poisoning in a limited-resource area: a 12-year retrospective study.

Amatoxin poisoning is the main cause of death from accidental ingestion of poisonous mushrooms and a mortality rate of 27.3% has been reported in Thailand. Symptoms of mushroom ingestion are often confused with food poisoning; thus, gastroenteritis is not recognised as the first phase of poisoning. Our study assessed the efficacy of N-acetylcysteine (NAC) as a treatment for amatoxin poisoning. We retrospectively analysed 74 medical records over 12 years. The majority (70/74) were treated successfully with NAC; death in the remaining 4 (5.4%) patients was attributed to late presentation in three and advanced alcoholic cirrhosis in one.

Lack of Transmission of Zika Virus Infection to Breastfed Infant.

Zika virus (ZIKV) continues to affect certain parts of the World. Here we report a case that supports breastfeeding regardless of mother ZIKV status by providing clinical and virological studies.