Severe Neurological Sequelae Research Articles

Spatial learning and memory impaired after infection of non-neurotropic influenza virus in BALB/c male mice

During the influenza pandemic or seasonal influenza outbreak, influenza infection can cause acute influenza-associated encephalopathy/encephalitis (IAE), even death. Patients with severe IAE will also have severe neurological sequelae. Neurologic disorders have been demonstrated in the mice treated with peripheral influenza viruses infection, whether neurotropic or non-neurotropic viruses. However, previous studies focused on the acute phase of infection, and rarely paid attention to a longer range of observations. Therefore, the long-term effect of non-neurotropic virus infection on the host is not very clear. In this study, adult mice were infected with influenza virus H1N1/PR8. Then, spontaneous behavior, body weight, expression of cytokines in brain, spatial learning ability and spatial memory ability were observed, until the complete recovery period. The results showed that cytokines in the brain were highly expressed in the convalescent phase (14 day post inoculation, dpi), especially BDNF, IBA1, CX3CL1 and CD200 were still highly expressed in the recovery phase (28 dpi). Otherwise the emotional and spatial memory ability of mice were impacted in the convalescent phase (14 dpi) and the recovery phase (28 dpi). In brief, BALB/c mice infected with non-neurotropic influenza virus H1N1, the weight and motor ability decreased in acute stage. During the recovery period, the body weight and activity ability were completely restored, whereas the emotion disordered, and the ability of spatial learning and memory were impacted in the infected mice. This long-term behavior impact may be the lag injury caused by non-neurotropic influenza infection.

Acute encephalopathy in children with tuberous sclerosis complex

ObjectiveWe examined the clinical manifestations of acute encephalopathy (AE) and identify risk factors for AE in children with tuberous sclerosis complex (TSC).MethodsThe clinical data of 11 children with clinically diagnosed TSC associated with AE and 109 children with clinically diagnosed TSC alone aged 4 years or older were collected from 13 hospitals.ResultsOf the 11 children with AE, 5 had histories of febrile seizures (FS), and all had histories of febrile status epilepticus (FSE). AE developed within 24 h after fever onset in all children with seizures lasting 30 min or longer. All children developed coma after seizure cessation. Head magnetic resonance imaging (MRI) revealed widespread abnormalities in the cerebral cortex, subcortical white matter, corpus callosum, basal ganglia, and thalamus. One child died; seven had severe neurological sequelae; and the other three, mild sequelae. Logistic regression analysis revealed that a history of FSE was correlated with the development of AE.SignificanceAE in children with TSC was characterized by sudden onset after fever, followed by coma, widespread brain edema evident on MRI, and poor outcomes. A history of FSE was a risk factor for the development of AE.

A less aggressive approach to the management of super refractory status epilepticus

Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic encephalopathy of unknown etiology. It commonly affects previously healthy children. FIRES is a subcategory of new-onset refractory status epilepticus (NORSE), term used specifically for adult population, and FIRES is used for pediatric population. Uniformly, both FIRES and NORES have poor outcomes with chronic drug-resistant epilepsy, severe neurological sequelae, and mortality in one-fifth of patients. We report a case of FIRES in a 9-year-old previously healthy child in whom a less aggressive approach was used to manage anesthetic resistant super refractory status epilepticus, which has reduced the potentially fatal complications of prolonged use of intravenous anesthetics and also the need for tracheostomy.

Hypoxic Ischemic Encephalopathy in Units Reporting to the Ibero-American Society of Neonatology Network: Prevalence and Mortality.

Hypoxic ischemic encephalopathy is a neurological condition occurring immediately after birth following a perinatal asphytic episode. Therapeutic hypothermia is a safe and effective intervention to reduce mortality and major disability in survivors. In Latin America, perinatal asphyxia is a major problem, but no data are available characterizing its current situation in the region or the impact of hypoxic ischemic encephalopathy on its management. Understand the prevalence, mortality and use of therapeutic hypothermia in newborns at ≥36 weeks gestational age with hypoxic ischemic encephalopathy admitted to neonatal units reporting to the Ibero-American Society of Neonatology Network. The Ibero-American Society of Neonatology Network groups various neonatology centers in Latin America that share information and collaborate on research and medical care. We evaluated data on newborns with ≥36 weeks gestational age reported during 2019. Each unit received a guide with definitions and questions based on the Society's 7th Clinical Consensus. Evaluated were encephalopathy frequency and severity, Apgar score, need for resuscitation at birth, use of therapeutic hypothermia and clinical evolution at discharge. Our analysis includes descriptive statistics and comparisons made using the chi-square test. We examined reports of 2876 newborns from 33 units and 6 countries. In 2849 newborns with available data, hypoxic encephalopathy prevalence was 5.1% (146 newborns): 27 (19%) mild, 36 (25%) moderate, 43 (29%) severe, and 40 (27%) of unknown intensity. In those with moderate and severe encephalopathy, frequencies of Apgar scores ≤3 at the first minute (p = 0.001), Apgar scores ≤3 at the fifth minute (p ⟨0.001) and advanced resuscitation (p = 0.007) were higher. Therapeutic hypothermia was performed in only 13% of newborns (19). Neonatal mortality from encephalopathy was 42% (61). Hypoxic ischemic encephalopathy is a neonatal condition that results in high mortality and severe neurological sequelae. In this study, the overall prevalence was 5.1% with a mortality rate of 42%. Although encephalopathy was moderate or severe in 54% of reported cases, treatment with hypothermia was not performed in 87% of newborns. These data reflect a regional situation that requires urgent action.

The combined vaccination protocol of DNA/MVA expressing Zika virus structural proteins as efficient inducer of T and B cell immune responses

ABSTRACT Zika virus (ZIKV) is a mosquito-borne pathogen with public health importance due to the high risk of its mosquito vector dissemination and the severe neurological and teratogenic sequelae associated with infection. Vaccines with broad immune specificity and control against this re-emerging virus are needed. Here, we described that mice immunized with a priming dose of a DNA plasmid mammalian expression vector encoding ZIKV prM-E antigens (DNA-ZIKV) followed by a booster dose of a modified vaccinia virus Ankara (MVA) vector expressing the same prM-E ZIKV antigens (MVA-ZIKV) induced broad, polyfunctional and long-lasting ZIKV-specific CD4+ and CD8+ T-cell immune responses, with high levels of CD4+ T follicular helper cells, together with the induction of neutralizing antibodies. All those immune parameters were significantly stronger in the heterologous DNA-ZIKV/MVA-ZIKV immunization group compared to the homologous prime/boost immunizations regimens. Collectively, these results provided an optimized immunization protocol able to induce high levels of ZIKV-specific T-cell responses, as well as neutralizing antibodies and reinforce the combined use of DNA-based vectors and MVA-ZIKV as promising prophylactic vaccination schedule against ZIKV.

Postnatal Maturation of Amplitude Integrated Electroencephalogram in Preterm SGA and Preterm AGA Neonates: A Prospective Observational Study

Introduction: Maturation of the brain is affected by various biological and environmental factors encountered by the infant during the intensive care period in Neonatal Intensive Care Unit (NICU) due to the medical treatments, procedures, and the noisy environment that disrupts the normal brain development process. Severe neurological sequelae of preterm infants are common because of the immature central nervous system. Cerebral Function Monitor (CFM) or Amplitude integrated Electroencephalogram (a-EEG) is a device for monitoring the background neurological activity. Aim: To assess postnatal maturation of a-EEG in clinically stable and neurologically normal preterm Small for Gestational Age (SGA) and preterm Appropriate for Gestational Age (AGA) neonates from 30 weeks 0/7 days to 34 weeks 6/7 days of gestation admitted in a tertiary care NICU at J. K. Lon Mother and Child Hospital, attached to Government Medical College, Kota. Materials and Methods: This prospective observational study was conducted over a one year duration, from January 2020 to December 2020 on 60 preterm neonates that were admitted in NICU of a tertiary care hospital. The serial a-EEG recording was done on haemodynamically stable, included preterm neonates after taking consent, on 3rd, 7th, and 14th postnatal day of life during the course of admission. The postnatal maturation of amplitude integrated EEG of Preterm Small for Gestational Age (PSGA) neonates was compared with their Preterm Appropriate for Gestational Age (PAGA) neonates based on a validated a-EEG scoring. The analysis was done by using Statistical Package for Social Sciences (SPSS) version 21.0. Student t-test was applied. Results: The total a-EEG scores for 3rd, 7th, and 14th day of SGA group neonates were 7.55±1.45, 7.25±1.02 and 10.22±1.05 and were delayed from the AGA group of neonates with 7.86±1.55, 8.68±1.00 and 10.62±1.01, with mean difference (95% CI), 0.30 (-0.49 to 1.13), 1.43 (0.88 to 1.97) and 0.39 (-0.15 to 0.95) respectively. Only the total a-EEG scores for day 7 were significantly delayed in SGA group. Conclusion: All the maturation a-EEG scores of clinically stable and neurologically normal PSGA neonates was found to be significantly delayed at any point of life on postnatal day 7th of life.

49. Clinical Characteristics of the 2019 Eastern Equine Encephalitis Virus Outbreak in Michigan

BackgroundEastern Equine Encephalitis Virus (EEEV) is a mosquito-borne alphavirus responsible for unpredictable outbreaks of severe neurologic disease in humans. While the vast majority of human EEEV infections are either asymptomatic or clinically nonspecific, a minority of patients develops neuroinvasive disease (EEE), which is a devastating illness with a mortality of at least 30%. No treatments are known to be effective. EEEV infection is relatively rare in the United States, with an annual average nationwide incidence of 7 cases between 2009 and 2018. However, 2019 was an exceptionally active year for human EEEV disease, yielding 38 nationwide confirmed cases, including 10 in Michigan, comprising the state’s largest outbreak to date.MethodsEEE cases were identified by a regional network of physicians. Cases were defined by presentation with clinical symptoms of encephalitis, and by identification of EEEV IgM antibodies or RNA in cerebrospinal fluid (CSF), or EEEV-specific IgM in serum as confirmed by plaque reduction neutralization test. Radiographic images were evaluated and clinical data abstracted through chart review and clinical follow-up where possible.ResultsRecords from 7 patients were identified and reviewed. The median age was 64, with a male predominance, and all presented in August. Notably, commercial arboviral CSF serology was uniformly negative on the initial CSF sample, and diagnosis was not made until a mean of 23 days (range: 12–38 days) after presentation. Testing in public health laboratories yielded the diagnosis in 5 out of 7 cases. Imaging findings were heterogeneous, but most patients exhibited abnormal findings in the thalamus and/or basal ganglia, and one patient displayed prominent pons and midbrain abnormalities. 4 patients died, while 2 patients survived with severe neurologic sequelae, and 1 patient recovered without sequelae. One patient underwent a limited postmortem examination, which revealed diffuse meningoencephalitis and focal vascular necrosis.ConclusionEEE is a frequently fatal condition whose diagnosis is often delayed, and for which no effective treatments are known. Improved diagnostics are needed to facilitate further clinical studies of EEE and encourage the development of potential therapies.Disclosures All Authors: No reported disclosures

Cognitive impairment without altered levels of cerebrospinal fluid biomarkers in patients with encephalitis caused by varicella-zoster virus: a pilot study

Varicella-zoster virus (VZV) is one of the most common agents causing viral infections of the central nervous system (CNS). VZV encephalitis is associated with severe neurological sequelae, despite antiviral treatment. Cognitive impairment has been reported and VZV has been associated with dementia. Our aim was to investigate the cognitive impairment and cerebrospinal fluid biomarkers in a follow-up study of patients with VZV encephalitis. Thirteen patients with VZV encephalitis, diagnosed by detection of VZV DNA in cerebrospinal fluid (CSF) by PCR and concomitant symptoms of encephalitis, were included. Neuropsychological assessment in parallel with a lumbar puncture to obtain CSF was performed 1.5–7 years after acute disease. The CSF biomarkers neurofilament light chain (NFL), S100B, glial fibrillary acidic protein (GFAP), amyloid-β (Aβ) 40 and Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) were analysed and compared to controls (n = 24). Cognitive impairment was shown in the domains of executive functions and speed/attention and to a minor degree in the domains of learning/memory and language, indicated by a significantly poorer performance on seven neuropsychological test variables. No convincing evidence of alterations in concentrations of biomarkers in the CSF were shown. Our results indicate that patients with VZV encephalitis suffer from cognitive impairment long time after acute disease. Importantly, these impairments do not seem to be accompanied by biomarker evidence of ongoing neuronal or astrocytic injury/activation or induction of dementia-related brain pathologies by the infection.

Clinical and Neuroimaging Characteristics of Pediatric Acute Disseminating Encephalomyelitis With and Without Antibodies to Myelin Oligodendrocyte Glycoprotein.

Objective: To compare the clinical and neuroimaging characteristics of anti-myelin oligodendrocyte glycoprotein antibody (MOG-ab) negative and positive pediatric acute disseminating encephalomyelitis (ADEM) patients.Methods: Clinical characteristics, neuroimaging features, ancillary examination results, and outcomes of pediatric ADEM patients were retrospectively reviewed between February 2016 and July 2019.Results: Among 37 pediatric ADEM patients, 24 patients (11 girls and 13 boys) fulfilled the inclusion criteria. The median age was 72 (range 19–156) months, and the median follow-up duration was 20 (range 12–48) months. Children with ADEM and MOG-abs presented with increased ataxia, reduced bladder/rectum dysfunction, and paralysis compared to children without MOG-abs. An important finding was that no significant differences existed in age at symptom onset, sex ratio, time from immunotherapy to clinical improvement and clinical recovery, or modified Rankin Scale (mRS) at the last follow-up. More typical cerebral MRI lesions were detected in patients with ADEM and MOG-abs than in children without MOG-abs [11/12 (91.7%) vs. 8/12 (66.7%)]. Cerebellar lesions were higher in ADEM patients with MOG-abs (7/12, 58.3%) than in those without MOG-abs (2/12, 16.7%). While seven children had abnormal spinal MRI findings (7/12, 58.3%) and five had longitudinally extensive transverse myelitis (LETM) (5/12, 41.7%) per group, the coexistence of spinal dysfunction and abnormal spinal MRI was lower in ADEM with MOG-abs (2/12, 16.7%) than in children without MOG-abs (7/12, 58.3%). Clinical improvement was achieved 1 week after immunotherapy. Most children in both groups achieved clinical recovery within 3 months after immunotherapy, although two (16.7%) patients with ADEM and MOG-abs had persistent neurological sequelae at the last follow-up.Conclusion: MOG-abs-positive ADEM is a major subtype of pediatric ADEM. Ataxia is the most common clinical presentation in pediatric ADEM and MOG-abs. Children with ADEM and MOG-abs have similar patterns of lesions characterized by large, bilateral, widespread lesions, as well as more cerebellar lesions than children without MOG-abs. Most spinal lesions were subclinical in pediatric ADEM with MOG-abs. A favorable prognosis can be achieved for pediatric ADEM regardless of the MOG-abs status. However, some patients with MOG-abs are likely to have more severe neurological sequelae.

Fat Embolism Syndrome in Sickle Cell Disease.

Fat embolism syndrome is a devastating complication of sickle cell disease resulting from extensive bone marrow necrosis and associated with high mortality rates, while survivors often suffer severe neurological sequelae. Despite that, the syndrome remains under-recognised and under-diagnosed. Paradoxically, it affects exclusively patients with mild forms of sickle cell disease, predominantly HbSC and HbSβ+. A significant number of cases occur in the context of human parvovirus B19 infection. We provide here a brief summary of the existing literature and describe our experience treating 8 patients in our institution. One patient had HbSS, 6 HbSC and 1 HbSβ+. All patients developed type I respiratory failure and neurological involvement either at presentation or within the first 72 h. The most striking laboratory abnormality was a 100-fold increase of the serum ferritin from baseline. Seven patients received emergency red cell exchange and 1 simple transfusion. Two patients (25%) died, 2 patients (25%) suffered severe neurological impairment and 1 (12%) mild neurological impairment on discharge, while 3 (38%) patients made a complete recovery. With long-term follow-up, 1 patient with severe neurological impairment and one patient with mild neurological impairment made dramatic improvements, making the long-term complete recovery or near complete recovery rate 63%. Immediate red cell exchange transfusion can be lifesaving and should be instituted as soon as the syndrome is suspected. However, as the outcomes remain unsatisfactory despite the increasing use of red cell exchange, we suggest additional therapeutic measures such as therapeutic plasma exchange and pre-emptive transfusion for high risk patients.

Intracranial Hemorrhage

Intracranial Hemorrhage

White Cerebellum Sign: case series and literature review

Introduction: The white cerebellum sign is a rare radiological finding, seen in severe traumatic brain injury and severe hypoxia. Radiologically, it is characterized by cerebellar hyperdensity, associated with diffuse cerebral hemispheres hypoattenuation. This paper aims to guide the white cerebellum sign diagnosis in traumatic craniocerebral injuries or not in pediatric patients. Patients and Methods: The authors present a series of five cases that showed the white cerebellum sign from the period about 2007 and 2010, associated with a literature review. Results: The white cerebellum sign was present in 5 patients, three of them were male and 2 female. The mean age was 22 months. The causes of which were: traumatic brain injury (3), drowning (1) and metabolic encephalopathy (1). The skull computerized tomography scan was performed in all cases. All patients were submitted to conservative treatment. There were four deaths and one survived with severe neurological sequelae. Conclusion: The white cerebellum sign is associated with irreversible brain damage, and its pathophysiology is controversial. The imaging tests are important to diagnosis. It has a poor prognosis, associated with the development of diffuse cerebral atrophy or cystic encephalomalacia in those who survive.

Intrauterine inflammation induced white matter injury protection by fibrinogen-like protein 2 deficiency in perinatal mice

BackgroundWhite matter injury (WMI) induced by intrauterine inflammation can cause adverse neurological outcomes. Fibrinogen-like protein 2 (FGL2)/fibroleukin is an important trigger of inflammatory responses and is involved in some cerebral diseases. However, the role of FGL2 in intrauterine inflammation-induced WMI remains unclear.MethodsLipopolysaccharide (LPS) was intraperitoneally injected into wild-type and FGL2 knockout mice to induce intrauterine inflammation. Body weight and brain weight of offspring were monitored. Major basic protein (MBP) expression was evaluated to demonstrate the myelination of offspring. To investigate the regulatory mechanism of FGL2, cytokine expression, microglial polarization, and the activation of mitogen-activated protein kinase (MAPK) signaling pathway in the offspring were analyzed.ResultsUpon LPS exposure, FGL2 knockout offspring showed a significant increase in body weight loss. MBP reduction induced by LPS was prevented in FGL2 knockout offspring. Expression levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α, and M1 marker CD86 were suppressed, while the expression levels of anti-inflammatory cytokines IL-10 and M2 marker CD206 were increased. FGL2 deficiency significantly inhibited the phosphorylation of p38MAPK and c-Jun N-terminal kinase (JNK) protein.ConclusionsFGL2 deficiency can ameliorate WMI induced by intrauterine inflammation, reducing inflammatory cascade and improving hypomyelination, through the regulation of microglial polarization and MAPK signaling pathways.ImpactIntrauterine inflammation induces WMI leading to severe neurological sequelae. FGL2 plays an important role in the progression of WMI induced by intrauterine inflammation.FGL2 deficiency can protect against WMI by inhibiting p38 MAPK and JNK phosphorylation, regulating microglia polarization, and reducing inflammation response.FGL2 could be a novel molecular target for protecting against WMI induced by intrauterine inflammation.

Severe Neurological Sequelae after a Recreational Dose of LSD.

A young man with an unremarkable medical history suffered a seizure with subsequent cardiorespiratory arrest and severe neurological sequelae after ingesting a blotter. Analysis of a similar blotter and a serum sample obtained 3 h after the event detected lysergic acid diethylamide (LSD) at an amount of 300 µg in the blotter and at a concentration of 4.0 ng/mL (12.4 nmol/L) in the serum. No other drugs were present in concentrations which may confer significant effects. In addition, no individual traits which would make the patient particularly susceptible to adverse LSD effects have subsequently been identified. This suggests that LSD may confer toxic effects in previously healthy individuals.

Vitamin B12 Deficiency in Newborns and their Mothers\u2014Novel Approaches to Early Detection, Treatment and Prevention of a Global Health Issue

SummaryVitamin B12 deficiency, mostly of maternal origin in newborns, is a well treatable condition but can cause severe neurologic sequelae. In women of childbearing age and pregnant women worldwide vitamin B12 deficiency has been reported with frequencies of 10%–50%. Children with vitamin B12 deficiency are asymptomatic at birth but may develop severe multisystemic symptoms, including irreversible developmental impairment in the second half-year of life. Early detection of vitamin B12 deficiency allows for presymptomatic treatment. This article provides an overview over the function of vitamin B12 and discusses causes and frequency of vitamin B12 deficiency in newborns, infants, and women of childbearing age. It describes novel successful approaches to newborn screening (NBS) for vitamin B12 deficiency and results of a pilot study which performed systematic NBS for vitamin B12 deficiency using so-called second-tier strategies by measuring homocysteine and methylmalonic acid in dried blood spots. Recommendations for diagnostics in mothers of children with vitamin B12 deficiency are described as well as results of systematic work-up in mothers and treatment and follow-up of children with vitamin B12 deficiency detected by NBS. Treatment options of vitamin B12 deficiency are presented including a newly developed standardized supplementation scheme with exclusively oral vitamin B12 supplementation. Recommendations for preventive approaches to vitamin B12 deficiency for children and mothers are stated. Many children worldwide could benefit from systematic inclusion of vitamin B12 deficiency into NBS panels. In addition, preventive approaches to maternal vitamin B12 deficiency should be implemented systematically during maternal care.

Adli Bir Olgu Olarak Çakmak Gazı İnhalasyonu ve Nörolojik Sekelleri

Uçucu maddelerin, bir diğer adıyla inhalan maddelerin tüm dünyada kullanımları giderek artmaktadır. Bu maddelerden kötüye kullanımı ile en sık karşılaşılanlardan biri, kolay ulaşılabilmesi, yasal olarak ve ucuza satın alınabilmesi, kısa sürede keyif verici etki göstermesi nedenleriyle çakmak gazıdır.
 Bu olgu sunumunda, yaklaşık üç yıl önce çakmak gazı inhalasyonu sonrası sokakta kardiak arrestte bulunan, yoğun bakım izlemi sırasında jeneralize tonik nöbet geçiren, kranial MRG’sinde hipoksik iskemik hasar ve bütan gazı inhalasyonuna sekonder değişiklikler izlenen, ağır motor ve mental nörolojik sekelleri saptanan 18 yaşındaki olgu sunuldu.
 Literatür taramasında daha çok çakmak gazı inhalasyonuna bağlı ani ölüm olguları ile ilgili otopsi çalışmaları olduğu görüldü. Sunulan olgunun, çakmak gazı inhalasyonu sonucu meydana gelebilecek nörolojik sekelleri belirgin bir şekilde ortaya koyması nedeniyle literatüre katkı sağlayacağı düşünüldü.

Biotin–Thiamine Responsive Basal Ganglia Disease Presented as Intractable Seizure in a 1-Month-Old Infant

AbstractBiotin–thiamine responsive basal ganglia disease is a neurometabolic disorder, seen in children presenting with encephalopathy, seizures, and positive family history. The disease is diagnosed based on typical magnetic resonance imaging (MRI) findings and whole exome sequencing but may be initially misdiagnosed as a mitochondrial encephalopathy or an inborn error of metabolism (IEM). We describe the case of an infant who presented with uncontrolled seizures and encephalopathy, responding to high doses of thiamine and biotin. Life-long supplementation of biotin (2–10 mg/kg/day) and thiamine (200–300 mg/day) improves the symptomatology and prevents relapse. Outcomes of the disease are heterogeneous, ranging in scope from complete remission to severe neurological sequelae.

Cerebral Venous Sinus Thrombosis in Women: Subgroup Analysis of the VENOST Study.

Background Early diagnosis of cerebral venous sinus thrombosis (CVST) associated with reproductive health-related risk factors (RHRF) including pregnancy, puerperium, and oral contraceptive (OC) use can prevent severe neurological sequelae; thus, the symptoms must be documented in detail for each group. Methods Out of 1144 patients with CVST, a total of 777 women were enrolled from a multicenter for the study of cerebral venous sinus thrombosis (VENOST). Demographic, biochemical, clinical, and radiological aspects were compared for 324 cases with RHRF and 453 cases without RHRF. Results The mean age of the RHRF (-) group (43.2 ± 13 years) was significantly higher than of the RHRF (+) group (34 ± 9 years). A previous history of deep venous thrombosis (3%), isolated cavernous sinus involvement (1%), cranial neuropathy (13%), comorbid malignancy (7%), and its disability scores after 12 months (9%) were significantly higher in the RHRF (-) group. The RHRF (+) group consisted of 44% cases of puerperium, 33% cases of OC users and 23% of pregnant women. The mean age was found to be higher in OC users (38 ± 9 years). A previous history of deep venous thrombosis was slightly higher in the pregnancy subgroup (4%). Epileptic seizures were more common in the puerperium group (44%). Conclusion The results of our study indicate that the risk of CSVT increases parallel to age, OC use, and puerperium period. In addition, when considering the frequency of findings and symptoms, epileptic seizures in the puerperium subgroup of the RHRF (+) group and malignancies in the RHRF (-) group may accompany the CSVT. In daily practice, predicting these risks for the CSVT and early recognition of the symptoms will provide significant benefits to patients.

Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus

Varicella-zoster virus (VZV) is a common cause of viral central nervous system (CNS) infection, and patients may suffer from severe neurological sequelae. The biomarker neurofilament light chain (NFL) is used for assessment of neuronal damage and is normally measured in cerebrospinal fluid (CSF). Novel methods have given the possibility to measure NFL in serum instead, which could be a convenient tool to estimate severity of disease and prognosis in VZV CNS infections. Here, we investigate the correlation of serum and CSF NFL in patients with VZV CNS infection and the association of NFL levels in serum and CSF with different VZV CNS entities. NFL in serum and CSF was measured in 61 patients who were retrospectively identified with neurological symptoms and VZV DNA in CSF detected by PCR. Thirty-three herpes zoster patients and 40 healthy blood donors served as control groups. NFL levels in serum and CSF correlated strongly in the patients with VZV CNS infection. Encephalitis was associated with significantly higher levels of NFL in both serum and CSF compared with meningitis and Ramsay Hunt syndrome. Surprisingly, herpes zoster controls had very high serum NFL levels, comparable with those shown in encephalitis patients. We show that analysis of serum NFL can be used instead of CSF NFL for estimation of neuronal injury in patients with VZV CNS infection. However, high levels of serum NFL also in patients with herpes zoster, without signs of CNS involvement, may complicate the interpretation.

No promising antidote 25years after the Tokyo subway sarin attack: A review.

On the battlefields of Syria, many innocent civilians have been killed or injured by sarin poisoning. In Malaysia in February 2017, a North Korean man was assassinated with VX at Kuala Lumpur International Airport. In the face of such threats, a more effective antidote against organophosphonate acetylcholinesterase (AChE) inhibitors is needed, one that can freely penetrate into the central nervous system (CNS) through the blood-brain barrier (BBB). In the 1995 Tokyo subway sarin attack, which produced more than 6,000 victims, 2-pyridinealdoxime methiodide was the most commonly used antidote in hospitals, but it was unable to prevent CNS damage and no other oximes have been approved for use in Japan. Ultimately, 12 people died, and many victims had severe neurological injuries or sequelae. Although more than 25years have passed since the incident, progress has been slow in the development of a new antidote that can penetrate the BBB, restore AChE activity in the CNS, and definitely prevent brain injury. From the perspectives of countering terrorism and protecting innocent people from nerve agent attacks, the search for nerve agent antidotes should be accelerated with the goals of improving both survival and quality of life. This review gives an overview of a series of our studies on the development of a new antidote since the Tokyo subway sarin attack and emphasizes that there is unfortunately still no promising antidote for saving the CNS in Japan.