Risk Of Neurological Sequelae Research Articles

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

Machine Learning Model for Predicting Mortality Risk in Pediatric Cerebral Venous Sinus Thrombosis

Introduction: Pediatric Cerebral Venous Sinus Thrombosis (CVST) is a rare but serious disorder with risk for neurologic sequelae and mortality. Prediction of health outcomes for risk stratification and tailored therapy is difficult based on available literature with single center studies and limited sample sizes. We sought to analyze the CVST data in Pediatric Health Information System (PHIS) database, a large, multicenter administrative database of pediatric inpatient data, to assess if supervised machine learning can assist in identifying pediatric CVST patients with increased risk of adverse outcomes. Methods: Patients 0 to 17 years of age with a diagnosis of CVST were identified in the PHIS database from 2011 to 2022. Demographic information, clinical characteristics, evaluation and management, and outcome data was extracted from diagnostic, imaging, procedure, and pharmaceutical billing codes. An XGBOOST model was fitted using 10-fold cross-validation with Bayesian optimization for hyperparameter tuning. The clinical parameters with values optimal for analysis from the “early era” (2011-2015) dataset were used to train for machine learning, and the test was applied to the “late era” (2016-2022) dataset. The final model was chosen based on the highest test set AUC score. The clinical parameters with significant SHAP values from the model were compared to published risk factors for mortality from an International Pediatric Stroke Study (IPSS) (RN Ichord, et al. Arch Dis Child 2015). Results: 6080 hospitalizations with CVST diagnosis (0.1% of all hospitalizations) were identified. The clinical parameters applied for machine learning included the following: age, gender, race, major complications (intracranial bleeding, hydrocephalus, coma), child opportunity index and ICU admission (Table 1.). The overall mortality rate at discharge was 4.2%. 2029 hospitalizations occurred in the early era and 4051 hospital admissions occurred in the late era. With the analyzable clinical parameters, the XGBOOST model could predict mortality with a probability of 0.7906. Of the clinical parameters used for machine learning (Figure 1), ICU admission, intracranial bleeding, hydrocephalus and coma had positive SHAP values indicating higher mortality risk prediction, whereas older age and being non-Hispanic white had negative SHAP values indicating lower mortality risk prediction. Similar risk associations for mortality were reported in the IPSS study, with patients with intracranial bleeding, younger age, and coma having higher mortality risk, consistent with our study finding. Conclusion: Our study in pediatric CVST, using machine learning, shows higher risk of mortality with ICU admission, and complications including intracranial bleeding, hydrocephalus, and coma; and lower risk of mortality with older age and non-Hispanic White status, which are consistent with IPSS study observations. Our study also illustrates how machine learning can be utilized by investigators to predict adverse clinical outcomes in pediatric CVST. In rare diseases which are difficult to study due to limited sample sizes like pediatric CVST, our study shows that data from large databases such as PHIS can be utilized for machine learning to predict health care outcomes, which can in turn inform future clinical practice to improve patient outcome.

Surgical management of mastoiditis with intratemporal and intracranial complications in children. Outcome, complications, and predictive factors.

Intratemporal or intracranial complications of acute mastoiditis are often of significant severity, can be life-threatening, and require prompt and usually aggressive treatment. This study focused on analyzing the outcomes and complications of different surgical techniques used in intracranial and intratemporal complications of acute mastoiditis, the most common complication of acute otitis media. A retrospective study of pediatric patients with mastoiditis with intratemporal and intracranial complications was designed at the Niño Jesús University Children's Hospital in Madrid, Spain, from 2005 to 2021. Of 417 patients with mastoiditis, 112 patients developed intratemporal and intracranial complications, with subperiosteal abscess being the most frequent complication. The most frequently isolated pathogens were Streptococcus pneumoniae, Streptococcus pyogenes, and Fusobacterium necrophorum. The most used surgical technique was myringotomy with placement of transtympanic drainage, in 86.6% of all cases. In patients with intracranial complications, neurosurgical procedures were necessary for 19.2%, with craniotomy with mastoidectomy being the most frequent. Most of the cases evolved favorably, and only 5.4% of the patients required surgical reintervention, being more frequent in intratemporal complications. In terms of complications, we found cases of neutropenia in 3.6%, neurological sequelae in 5.4%, and permanent hearing loss in 2.7%. There was a favorable evolution with a low incidence of reoperation and sequelae within our series. The surgical technique of choice correlated with the severity of the complication. If the mean size of the abscess exceeds 20mm, incision and drainage, along with myringotomy and tube placement, should be considered as the initial treatment. Closed mastoidectomy should be reserved for deteriorating of clinical evolution or acute mastoiditis with intracranial complications. Intracranial and multiple concomitant complications were associated with a more extended hospital stay, ICU occupancy, neurosurgical intervention, and risk of neurological sequelae and neutropenia. Conversely, intratemporal complications may result in permanent hearing loss.

Galen's Ampulla Aneurysm: A Case Report

Introduction: Galen's vein aneurysm is a rare complex intracranial arteriovenous malformation, associating pseudo-aneurysmal dilation of Galen's ampulla with one or more arteriovenous fistulas. The prognosis is often poor, with high mortality and a risk of neurological sequelae. Objective: To support the role of imaging in the diagnosis, with illustration by two observations collected within our Radiopediatrics department of the CHU Mohammed VI of Marrakech, having benefited from a cerebral angio-scanner. Case Report: 1st case:is an 18-month-old infant with no particular history presenting macrocrania with generalized seizures.2nd case:is also a 2-year-old infant, with the appearance of a vein in the suborbital groove for 6 months, with no other associated signs.3rd patientis a 1-year-old infant with macrocrania with signs of HTIC. 4th case6-month-old boy, presents with HTIC syndrome. Objective cerebral CT in the first three patients: a rounded median mass, in the pineal region behind the 3rd ventricle, slightly hyperdense in spontaneous contrast; CT angiography proves the vascular nature of the lesion by showing intense and homogeneous enhancement after injection of PDC, associated with dilation of the venous sinuses, and moderate passive triventricular hydrocephalus by compression of the aqueduct of Sylvius. The fourth patient benefited from a transfontanellar ultrasound which objectified an anechoic interhemispheric fusiform structure presenting a vascular flow to the color Doppler. Conclusion: The aneurysmal malformation of the Vein of Galen (AVGM) is a rare vascular malformation, specific to children, discovered ante or post natally, in fact only corresponds to a venous dilation draining an arterio-venous malformation, whose system afferent arterial comes from the carotid system or the vertebro-basilar axis; it results from the absence of differentiation in the mature arterio-venous system, between 7 and 12 SA, of a primitive, median embryonic vein which ......

Molecular and cellular biomarkers in status epilepticus and epilepsy

Introduction. Peripheral biomarkers have numerous uses in the treatment, prognosis, and pharmacovigilance of epilepsy. Unfortunately, no peripheral biomarker has demonstrated proven efficacy, although several options are being investigated. In this article, we want to analyze the main areas in which peripheral biomarkers can present their usefulness, including participation in the processes of inflammation, dysfunction of the blood-brain barrier, changes in metabolism, hormones, and growth factors. Material and methods. Publications on diagnostic biomarkers of epilepsy were reviewed. References were identified by PubMed, MEDLINE and Scopus search until June 2022, with various combinations of the terms – „epilepsy”, „seizures”, „epileptogenesis”, „biomarkers”, „neuroimaging”, „inflammation”, „status epilepticus”, „prognosis”. A qualitative and analytical study was performed focused on primary studies published in 2020-2022. More than 85 sources were identified and 33 were selected for analysis from the PubMed, MEDLINE, and Scopus online databases. 12 articles, 5 clinical trials, 2 meta-analyses, 7 reviews, and 7 systematic reviews were identified. Results. Screening articles from online databases according to the search criteria, we found 258 titles on molecular and cellular biomarkers in epilepsy highlighted. The final bibliography included 33 sources that summarized that biomarkers of epileptogenesis are expensive and difficult to research, but the identification of biomarkers specific to the entire epileptogenic process, in close proximity to neuronal damage, have demonstrated the possibility of predicting the risk of seizures, epilepsy and resistance to treatment. Conclusions. Epilepsy remains a continuous area of research; a special role is occupied by specific biomarkers of great clinical importance, being necessary for the prognosis of the disease, the risk of neurological sequelae, refractory to anti-epileptic drugs. Thus, their identification could have a significant impact on the clinical course of the disease.

Imaging findings in abusive head trauma (AHT).

Brain imaging plays a key role in accurately identifying abusive head trauma (AHT). An exact and rapid diagnosis is needed due to the extreme severity of AHT, since there is a risk of neurological sequelae and potentially fatal recurrence. Several medical specialists will work collaboratively to detect and confirm abuse in children: the radiologist has a leading role in this approach. This article describes the most common neuro-imaging patterns of AHT, including extra axial, intra axial, bony, and ligamentous lesions, with a special focus on the dating issue and the differential diagnosis.

Discharge of newborns with risk factors of severe hyperbilirubinemia: description of a hospital at home-based care monitoring and phototherapy.

Neonatal jaundice is common and associated with delay in hospital discharge and risk of neurological sequelae if not treated. The objectives of the study were to report on our experience of the monitoring and treatment of neonatal jaundice in a home care setting and its feasibility and safety for neonates with high risk of severe hyperbilirubinemia. The 2-year study has been led in the greater Paris University Hospital At Home (Assistance Publique-Hôpitaux de Paris). The device of the intervention was the Bilicocoon® Bag, a light-emitting diode sleeping bag worn by the neonate when the total serum bilirubin value exceeds intensive phototherapy threshold, according to the guidelines from the American Academy of Pediatrics. One hundred and thirty-nine neonates had participated in the intervention and 39 (28%) were treated by phototherapy at home, as continuation of inpatient phototherapy or started at home. Seventy-five percent of the sample had more than two risk factors for development of severe hyperbilirubinemia. Twenty five percent of the cohort who received phototherapy at home had lower gestational age (p < 0.014) and had younger age at discharge from maternity (p < 0.09). Median length of stay in hospital at home was 5days. Two patients needed readmission in conventional hospital (1%) for less than 24h. In multivariate model, the length of stay decreased with the higher gestational age (p < 0.001) and increased significantly with the older age at discharge, the birth weight < 10th percentile, and a treatment by phototherapy at home. Conclusion: Hospital at home, which is a whole strategy using an effective and convenient phototherapy device combined with a specialized medical follow-up, could be an alternative to conventional hospitalization for neonates at high risk of severe jaundice. The maternity discharge is facilitated, the mother-infant bonding can be promoted, and the risk of conventional rehospitalization is minimal, while guaranteeing the safety of this specific care. What is Known: • Managing neonatal jaundice is provided in conventional hospital with phototherapy. • Neonatal jaundice increases the risk of prolonged hospitalization or readmission. What is New: • Phototherapy is feasible in hospital at home for neonates with high risk of severe hyperbilirubinemia. •The care pathway of neonates from conventional hospital to hospital at home is described.

Anticoagulation in Acute Neurological Disease.

While anticoagulation and its reversal have been of clinical relevance for decades, recent academic and technological advances have expanded the repertoire of its application in neurological disease. The advent of direct oral anticoagulants provides effective, mechanistically elegant, and relatively safer therapeutic options than warfarin for eligible patients at risk for neurological sequelae of prothrombotic states, particularly given the recent availability of corresponding reversal agents. In this review, we examine the provenance, indications, safety, and reversal tools for anticoagulant medications in the context of neurological disease, with specific attention to acute ischemic stroke, cerebral venous sinus thrombosis, and intracerebral hemorrhage. We will use specific clinical scenarios to illustrate the complex factors that must be considered in the use of anticoagulation, including intracranial pathology such as intracerebral hemorrhage, traumatic brain injury, or malignancy; metabolic complications such as chronic kidney disease; pregnancy; and advanced age.

EBV Reactivation Incidence and Severity in Multiple Sclerosis Patients Treated with Autologous Haematopoietic Stem Cell Transplant and Comparing with Aplastic Anaemia Treated with ATG—Single Site Experience

INTRODUCTION: Autologous haematopoietic stem cell transplant(HSCT) with anti-thymocyte globulin (ATG) based conditioning is currently being explored for its efficacy and safety in the treatment of Multiple Sclerosis (MS). Despite increasing experience gained, the procedure still carries significant risk of morbidity. Epstein Barr Virus (EBV) infection and its role in pathogenesis of MS remain undetermined. EBV reactivation and post-transplant lymphoproliferative disorders (PTLD) are well described in allogeneic HSCT and uncommon with auto HSCT for other malignant conditions. Similarly patients with Aplastic anaemia (AA) treated with standard immunosuppressive therapy with ATG/ciclosporin also have increased risk of EBV reactivation but reports of PTLD in this group are very rare. The incidence of clinically significant EBV reactivation in MS patients undergoing HSCT is increasingly recognised. This retrospective study reports rates of EBV reactivation, PTLD incidence and associated clinical sequelae in patients with MS undergoing HSCT as compared with AA patients receiving ATG in our centre.PATIENTS AND METHODS: 36 patients with MS had AHSCT between Feb 2012 and 2017. 35 were conditioned using standard protocol of cyclophosphamide and ATG (2.5mg/kg/day for 3 days), and one with BEAM-ATG. A Comparator group of 40 patients with AA consecutively treated with ATG (40mg/kg/day for 4 days) between Sept 2013 and Nov 2016 was selected. Prior exposure to EBV (EBV IgG) was assessed pre-HSCT. EBV levels monitoring was performed on whole blood samples by quantitative polymerase chain reaction (PCR) as per standard centre protocol. Data was collected retrospectively.RESULTS: All patients had previous EBV exposure. All MS patients with relapsing remitting (n=22) and primary/secondary progressive (n=14) disease were previously treated with median 2 (range, 0-6) disease modifying therapies (DMT) and 23 had at least 1 highly active DMTs. Median age of 43yrs (range, 22-64yrs) versus 52yrs (range, 19-68yrs) in AA group, with 35 patients severe/very severe AA and 5 non-severe treated with ATG. Where follow up data was available there was no difference in EBV reactivation rates (80.6% vs 65% P-0.13). The median time to EBV detection was 28 days (IQ range, 19-41d) vs 11 days (IQ range 5-39 d)with a maximal EBV DNA titre at median of 39 days (IQ range 29.5-49.5d) vs 11.5 days(IQ Range 0-43.5) in MS and AA cohort respectively.Patients were stratified into their maximum level of reactivation based on the amount of EBV copy numbers; 0-100,000 copies, 100,000 - 500,000 copies and >500,000 copies. In MS group (Table 1), 8 patients had symptomatic EBV reactivation; defined as persistent fever, lymphadenopathy and/or B symptoms. 10 (34.5%) MS patients had EBV copies>500,000. 3 of these had findings consistent with PTLD on CT scan, however none had histological diagnosis. 3 other MS patients had worsening neurological symptoms with one presenting as pseudo-relapse. All 6 of these patients were treated with anti-CD20 monoclonal therapy (Rituximab; 375mg/m2 weekly for 4 weeks) with rapid resolution of their symptoms. MS patients were more likely to develop high EBV (>500k) levels (p-0.03) and receiver operating characteristics (ROC) curve analysis (Fig 1) confirmed high EBV levels>500,000 correlate with high sensitivity 85.5%, specificity 82.5% (p-0.004) for clinical events requiring treatment. No significant rituximab related adverse events noted in treated group. As expected, no significant symptomatic EBV and no PTLD events were noted in AA cohort and none required any rituximab therapy for the EBV reactivations.Significantly raised paraproteinaemia was observed in 21 (72.4%) of MS cohort compared to 3 (11.5%) in the AA group (p < 0.01). 3 of the MS cohort experienced paraprotein levels greater than 20 g/L and one (IgG 61.1g/L) developed hyper-viscosity requiring plasma exchange and developed neurological symptoms mimicking a MS relapse.CONCLUSION: EBV reactivation was observed to occur commonly in patients with MS with significant symptoms and risk of neurological sequelae and PTLD events in this group, which is unlike the AA cohort treated with comparable ATG doses. Regular EBV monitoring in first 3 months should be mandated in MS patients undergoing HSCT and we recommend cut-off of 500,000 copy numbers as trigger for consideration of pre-emptive rituximab therapy. [Display omitted] DisclosuresPotter:Jazz: Honoraria; Pfizer: Other: Advisory board. Raj:Celgene: Speakers Bureau; Mallinckrodt: Speakers Bureau; MSD: Speakers Bureau; Bloodwise: Research Funding. Pagliuca:Bluebird: Honoraria; Gilead: Honoraria; Astellas: Consultancy, Speakers Bureau; Pfizer: Honoraria; Merck: Honoraria, Research Funding; Jazz: Honoraria; Basilea: Honoraria.

Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis

BackgroundTuberculous meningitis is the most devastating presentation of disease with Mycobacterium tuberculosis. We sought to evaluate treatment outcomes for adult patients with this disease.MethodsThe Ovid MEDLINE, EMBASE, Cochrane Library and Web of Science databases were searched to identify all relevant studies. We pooled appropriate data to estimate treatment outcomes at the end of treatment and follow-up.ResultsAmong the articles identified, 22 met our inclusion criteria, with 2437 patients. In a pooled analysis, the risk of death was 24.7% (95%CI: 18.7–31.9). The risk of neurological sequelae among survivors was 50.9% (95%CI: 40.2–61.5). Patients diagnosed in stage III or human immunodeficiency virus (HIV) positive were significantly more likely to die (64.8, 53.4% respectively) during treatment. The frequency of cerebrospinal fluid (CSF) acid-fast-bacilli smear positivity was 10.0% (95% CI 5.5–17.6), 23.8% (15.2–35.3) for CSF culture positivity, and 22.3% (17.8–27.5) for CSF polymerase chain reaction positivity. We found that the headache, fever, vomiting, and abnormal chest radiograph were the most common symptoms and diagnostic findings among tuberculous meningitis patients.ConclusionsDespite anti-tuberculosis treatment, adult tuberculous meningitis has very poor outcomes. The mortality rate of patients diagnosed in stage III or HIV co-infection increased significantly during treatment.

Clinical features, outcomes and prognostic factors of tuberculous meningitis in adults worldwide: systematic review and meta-analysis.

Tuberculous meningitis (TBM) is one of the most life-threatening infectious diseases. We performed a systematic review and meta-analysis of the clinical features, outcomes, and prognostic factors for TBM in adults. PubMed, EMBASE, Cochrane CENTRAL, and Web of Science were searched for studies that reported the clinical outcomes and/or risk factors for death in adults with TBM between January 1990 and July 2018. A random-effects meta-analysis model was used to pool data on clinical features, outcomes, and risk factors for death. Thirty-two studies that examined 5023 adults who had TBM met the inclusion criteria. Overall, the mortality was 22.8% [95% confidence interval (CI) 18.9-26.8] and the risk of neurological sequelae was 28.7% (95% CI 22.8-35.1). The major risk factors for death (OR > 2 and P < 0.05) were advanced stage of disease (OR = 6.06, 95% CI 4.31-8.53), hydrocephalus (OR = 5.27, 95% CI 2.25-12.37), altered consciousness (OR 3.33, 95% CI 1.51-7.36), altered sensorium (OR 3.31, 95% CI 2.20-4.98), advanced age (> 60years; OR = 2.64, 95% CI 1.27-5.51), and cerebral infarction (OR = 2.35, 95% CI 1.63-3.38). The clinical features and diagnostic findings present in more than four-fifths of the patients were fever (86.3%, 95% CI 82.4-89.8) and low CSF/serum glucose ratio (80.6%, 95% CI 64.8-92.6). Adults with TBM have high rates of mortality. Clinicians should maintain a high clinical suspicion for patients who present with certain clinical features, and should pay more attention to prognostic factors.

Neurologic morbidities, psychological distress, and functional independence in adult survivors of childhood cancer treated with CNS-directed therapies: A report from the Childhood Cancer Survivor Study.

10570Background: Survivors of childhood cancer who received CNS-directed therapies are at risk for neurologic sequelae, which may adversely impact psychological functioning and independence in adul...

The role of EEG recordings in children undergoing cardiac surgery for congenital heart disease.

Neurological dysfunction may occur after corrective cardiac surgery using cardio-pulmonary bypass (CPB) with or without circulatory arrest. Different neurophysiological monitoring systems have been employed to detect neurological complications and possible brain injury in infants and children during and after cardiac surgery. The value of Elecetroencephalogram (EEG) in infants and children at risk for neurological sequelae has not been systematically studied. Sequential performance of two EEGs before and after cardiac surgery at atertiary University Hospital to screen for possible brain injury after cardiac surgery in neonates and children undergoing CPB surgery. In addition, acomplete neurological examination and assessment by aphysiotherapist was performed. Over a4-year period, in 313patients (age: 54.2± 55.7months; normal initial EEG) after cardiac surgery CPB (duration of surgery: 146.0± 58.9 min; aortic cross clamp time: 34.1± 19.1 min), a19-channel EEG recording was performed 2.4± 1.8days prior to and 11.6± 5.3days after cardiac surgery. An abnormal EEG was detected in only 8 of 313patients (2.5%; focal slowing:1, generalised slowing:5, epiletiform discharges:2) after cardiac surgery, while the EEG was normal in the remaining 305patients (97.5%). In 1patient, an intra-cerebral pathology was seen on MRI (ischemic); in 5patients, follow-up EEGs were performed, which revealed normalized findings. None of the 8patients demonstrated new focal neurological deficits on physical examination, but 33(9.7%) children demonstrated minor abnormalities (e.g., subtle motor asymmetry, increase in muscle tone, etc.), which were unrelated to abnormal EEG findings. According to the used protocol, pathological EEG findings were very infrequent in our study cohort. The routine and indiscriminative recording of EEGs in children before and after corrective or palliative cardiac surgery for congenital heart disease using CPB is not recommended. Further intra-operative neuromonitoring methods with immediate intervention should be evaluated.

Prevalence, Aetiology and Outcome of Status Epilepticus in Children with Convulsions at the Wesley Guild Hospital, Ilesa

Status epilepticus (SE) in childhood is a life threatening condition with serious risk of neurological sequelae and constitutes a medical emergency. The aim of this study is to provide data on the prevalence, aetiology and outcome of status epilepticus in children at the Wesley Guild Hospital, Ilesa, South-West Nigeria. We prospectively studied all the 276 children who were admitted with convulsion over a period of seven months, out of which 39 (14.1%) had status epilepticus. The cause of status epilepticus in 82.1% of the patients was cerebral malaria; other causes were febrile convulsion, meningitis, seizure disorders and head injury. The mortality and morbidity (neurologic sequelae at discharge) in this study were 23.1% and 33.3%, respectively. Mortality and morbidity were significantly higher in children who had status epilepticus compared to those who convulsed but did not have status. (χ2=33.773, df=1, p<0.001), (χ2=43.991, df=1, p<0.001). In conclusion, morbidity and mortality of SE is high and control of malaria will most likely reduce the prevalence and improve the outcome of SE in this environment.

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

Tick-Borne Encephalitis sequelae at long-term follow-up: a self-reported case-control study.

Tick-borne encephalitis (TBE), caused by the TBE virus (TBEV), is a major neurotropic infection throughout Europe and Asia, with a considerable risk of neurological sequelae. Our aim was to study the symptoms in patients with TBE in Western Gotaland between 1997 and 2012 in the acute phase and at follow-up after 2-15 years (median: 5.5 years). The medical records of 96 patients with TBE were studied. Phone-based interviews were held with 92 patients and 58 controls, matched by age, gender and residential area. The Encephalitis Support Group Questionnaire (ESGQ) 2000 was used, further developed with dimensions and scoring 1-4, where a high score is related to better outcome. Patients and controls also answered a written survey regarding functional outcome of sleep (FOSQ). Of the patients, 35% had a mild disease, 56% moderate and 7.3% severe disease. At the follow-up, patients scored significantly lower than controls in the dimensions of memory/learning, executive functions, vigilance and physical impairments. In addition, the answers concerning tiredness/fatigue, poor concentration/attention, reduced initiative/motivation, balance disturbances, coordination problems, difficulties with short- and long-term memory, learning difficulties and problems with fine motor skills resulted in significantly lower scores in the patients compared with the controls. The patients scored lower than the controls in the FOSQ dimension social outcome. At the long-term follow-up, the patients scored significantly lower in a diversity of neurocognitive and motor symptoms, in comparison with controls. These sequelae and their pathogenesis should be further explored and specific neurocognitive assessment tests are needed.

Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection via Breast Milk: A Two-Year Prospective Follow-Up Study.

Approximately 15% of preterm infants may develop postnatal cytomegalovirus (CMV) infection from seropositive mothers via breast milk and are at risk for neurological sequelae in childhood. The aims of this study were to assess the effects and outcomes on growth, neurodevelopmental status, and hearing in very low birth weight (VLBW) premature infants with postnatal CMV infection via breast milk at the corrected age of 12 and 24 months.The prospective follow-up study population comprised all living preterm children (n = 55) with a birth weight ≤1500 g and gestational age of ≤35 weeks, who had been participated in our “postnatal CMV infection via breast milk” studies in 2000 and 2009, respectively. The cohort of children was assessed at 12 and 24 months. Clinical outcomes were documented during hospitalization and after discharge. Long-term outcomes included anthropometry, audiologic tests, gross motor quotient, Infant International Battery, and neurodevelopmental outcomes; all were assessed at postcorrected age in 12 and 24 months during follow-up visits.Of the 55 infants enrolled in the study (4 noninfected infants were excluded because their parents did not join this follow-up program later), 14 infants postnatally acquired CMV infection through breast-feeding (infected group) and were compared with 41 infants without CMV infection (control group). No significant differences were observed between the groups with regard to baseline characteristics, clinical outcomes, anthropometry, or psychomotor and mental development on the Bayley scale of infant development. None of the infants had CMV-related death or permanent sensorineural hearing loss.Transmission of CMV from seropositive mother via breast milk to preterm infants does not appear at this time to have major adverse effects on clinical outcomes, growth, neurodevelopmental status, and hearing function at 12 and 24 months corrected age.

The role of EEG recordings in children undergoing cardiac surgery for congenital heart disease.

Neurological dysfunction may occur after corrective cardiac surgery using cardio-pulmonary bypass (CPB) with or without circulatory arrest. Different neurophysiological monitoring systems have been employed to detect neurological complications and possible brain injury in infants and children during and after cardiac surgery. The value of EEG in infants and children at risk for neurological sequelae has not been systematically studied. Sequential performance of 2 EEGs before and after cardiac surgery at a tertiary University Hospital to screen for possible brain injury after cardiac surgery. In addition, a complete neurological examination was performed. In 313 patients (age: 54.2±55.7 months; normal initial EEG) after cardiac surgery CPB (duration of surgery: 146.0±58.9 minutes; aortic cross clamp time: 34.1±19.1 minutes) a 19-channel EEG recording was performed 2.4±1.8 days prior and 11.6±5.3 days after cardiac surgery. An abnormal EEG was detected in only 8 of 313 patients (2.5%; focal slowing(1), generalised slowing (5), epiletiform discharges(2)) after cardiac surgery, while the EEG was normal in the remaining 305 patients (97.5%). In one patient, an intra-cerebral pathology was seen on MRI (ischemic); in 5 patients follow-up EEGs were performed, which revealed normalised findings. None of the 8 patients demonstrated new focal neurological deficits on physical examination, but 33 (9.7%) children demonstrated minor abnormalities (eg, subtle motor asymmetry, increase in muscle tone, etc.), which were unrelated to abnormal EEG findings. According to the used protocol pathological EEG findings were very infrequent in our study cohort. The routine and indiscriminative recording of EEGs in children before and after corrective or palliative cardiac surgery for congenital heart disease using CPB is not recommended. Further intra-operative neuromonitoring methods with immediate intervention should be evaluated.

Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

BackgroundMeningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D.MethodsIn vivo, we studied the effects of vitamin D3 on survival and the host’s immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured.ResultsMice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation.ConclusionOur observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis

Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0-26·1) and probability of survival without neurological sequelae was 36·7% (27·9-46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6-64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5-100·0), CSF lymphocytosis (97·9%, 51·9-100·0), fever (89·8%, 79·8-95·2), and hydrocephalus (86·1%, 68·6-94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0-15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8-59·2). Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. None.