Role of cerebrospinal fluid tau protein levels as a biomarker of brain injury in pediatric status epilepticus.

BACKGROUND: Various biomarkers have been studied for predicting etiology and outcome in status epilepticus (SE); cerebrospinal fluid (CSF) total tau (t-tau) protein levels is foremost among them. Only handful of studies are available regarding role of t-tau in childhood SE. METHODOLOGY: This prospective study was conducted in a tertiary care center of Northern India in children 6 months -12 years of age. The Cases were patients with convulsive status epilepticus (CSE) whereas Controls were patients without SE and normal CSF. The t-tau levels were done in CSF of both the groups. The outcome was assessed by GOS-E Peds score. RESULTS: A total of 50 (62% males) cases and 15 (67% males) controls were enrolled in the study. SE was generalized in 78% cases whereas 14% had refractory SE. Most common etiology of CSE was acute symptomatic (52%), followed by prolonged febrile seizure (24%), remote symptomatic group (14%), unknown etiology (8%) and progressive disorder (2%). Case fatality rate was 10%. Poor outcome was seen in 30% cases. Median (IQR) CSF t-tau levels was significantly lower 2.6 × 103 (0.5-9.4 × 103) pg/ml in cases vs 10.6 × 103 (6.0-14.2 × 103) pg/ml in controls (p = 0.004). There was no significant correlation seen between type, duration, etiology and response to antiepileptic drugs of SE with CSF t-tau levels. Also, no significant correlation of poor sensorium, outcome of SE and critical care needs with CSF t-tau levels was noted. CONCLUSION: CSF t-tau is not a useful diagnostic or prognostic biomarker in pediatric SE.

The new Xpert Mycobacterium tuberculosis/rifampicin (MTB/Rif) Ultra assay in comparison to Xpert MTB/Rif assay for diagnosis of tuberculosis in children and adolescents.

BACKGROUND: Microbiological diagnosis of pediatric tuberculosis (TB) using conventional microbiological techniques has been challenging due to paucibacillary nature of the disease. Molecular methods using cartridge-based tests like Xpert, have immensely improved diagnosis. A novel next-generation cartridge test, Xpert Ultra, incorporates two additional molecular targets and claims to have much lower detection limit. We attempted to compare the two techniques in presumptive pediatric TB patients. OBJECTIVES: The aim of this study was to compare the diagnostic performance of Xpert MTB/Rif Ultra with Xpert MTB/Rif for the detection of pediatric TB. STUDY DESIGN: This is an observational comparative analytical study. METHODS: Children under 15 years of age with presumptive TB were enrolled. Appropriate specimens were obtained (sputum, induced sputum or gastric aspirate for suspected pulmonary TB, cerebrospinal fluid for suspected tubercular meningitis and pleural fluid for suspected tubercular pleural effusion), subjected to smear microscopy, mycobacterial culture, Xpert and Xpert ultra tests and other appropriate diagnostic investigations. RESULTS: Out of 130 enrolled patients, 70 were diagnosed with TB using a composite reference standard (CRS). The overall sensitivity of Xpert was 64.29% [95% confidence interval (CI) 51.93-75.93%] and that of Xpert Ultra was 80% (95% CI 68.73-88.61%) with 100% overall specificity for both. The sensitivity of Xpert and Xpert Ultra in pulmonary specimens (n = 112) was 66.67% and 79.37% and in extrapulmonary specimens (n = 18) was 42.86% and 85.71%, respectively. CONCLUSION: Our study found Ultra to be more sensitive than Xpert for the detection of Mycobacterium tuberculosis in children. Our findings support the use of Xpert Ultra as initial rapid molecular diagnostic test in children under evaluation for TB.

Early diagnosis of kidney injury in a paediatric population: a prospective cohort study (E-DRIP STUDY).

BACKGROUND: Renal Angina Index (RAI) is a bedside tool for risk stratification of patients to predict acute kidney injury (AKI). Kidney biomarkers are better indicators of real-time injury and give us lead time for diagnosing impending AKI. METHODS: We enrolled consecutive children aged 2 months-14 years admitted to a tertiary hospital in northern India over 2 years. RAI was calculated on day 0 (D0) and urinary (u) and plasma (p) neutrophil gelatinase-associated lipocalin (NGAL) were measured within 6 h of admission. Children were followed for the development of severe AKI on day 3 (D3) using Kidney Disease Improving Global Outcomes criteria to define and stage AKI. RESULTS: Of the 253 children enrolled and analysed, 44 (17.4%) developed D3-AKI (stage 1 in 52.2%, stage 2 in 20.5% and stage 3 in 27.3%). Renal angina (RAI ≥ 8) on D0 was present in 66.7% children who developed stage 2/3 D3-AKI vs. 43.5% in children who did not develop D3-AKI /stage 1 AKI (p = 0.065). Area under ROC (AUROC) curve for D0-RAI to predict D3-severe-AKI was 0.66 (95% CI, 0.55-0.77). AUROC curve for uNGAL and pNGAL to predict D3-severe-AKI was 0.62 (95% CI, 0.50-0.74) and 0.48 (95% CI, 0.35-0.61), respectively. The severe AKI group had greater requirement of ventilation and inotropic support with mortality being thrice higher compared to the non-AKI group. CONCLUSION: RAI ≥ 8 and uNGAL had a high negative predictive value but low sensitivity for predicting D3-severe-AKI. pNGAL had a poor predictive value for D3-severe-AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute disseminated encephalomyelitis due to a zoonotic co-infection.

Acute disseminated encephalomyelitis (ADEM) is a post-infectious, autoimmune, demyelinating neurological illness, usually attributed to infection with viruses. We describe a case of ADEM occurring in a child with Leptospira-Brucella co-infection. The 12-year-old girl developed a biphasic febrile illness with encephalopathy. On evaluation, she was found to have serological evidence of Brucella and Leptospira infections. Persistence of neurological symptoms after initiating treatment for the co-infection led us to do a magnetic resonance imaging scan of the brain which showed typical findings suggestive of ADEM. Patient responded appropriately to treatment of ADEM with glucocorticoids. The high prevalence of these zoonotic infections in developing countries, and the risk that these may lead to ADEM highlights the importance of detailed evaluation of such cases for proper treatment and better outcomes.

ADEM is a serious neurological disease which occurs as an uncommon complication of certain infections that lead to formation of antibodies which attack the cells of the nervous system. It usually occurs after viral infections, but we came across a 12-year-old girl with ADEM who tested positive for simultaneous infection with two different micro-organisms, both not viruses. These microbes, called Leptospira and Brucella, are common in developing countries and usually lead to infection in individuals in close contact with animals, or with consumption of infected, unpasteurized animal products. Neurological symptoms are uncommon in both infections. However, our case highlights that both infections can occur together and lead to serious neurological illness which needs proper evaluation and a different kind of treatment so that patient has better recovery.

Spectrum of Multiorgan Dysfunction in Scrub Typhus Infection.

OBJECTIVES: We planned this study to determine the clinical spectrum and compare incidence of multiorgan dysfunction in children hospitalized with scrub typhus with other etiologies of tropical fever. DESIGN: Prospective cohort study. SETTING: Pediatric emergency and PICU services of a university teaching hospital situated in the sub-Himalayan region. PATIENT: Children aged 2 months to 14 years with acute undifferentiated fever of more than 5 days. INTERVENTIONS: Detailed fever workup was performed in all children. We compared scrub typhus IgM positive children (cases) with remaining febrile children who were negative for scrub IgM assay (controls) for mortality and morbidity. MAIN RESULTS: We enrolled 224 febrile children; 76 children (34%) were positive for scrub typhus IgM ELISA. Scrub typhus group had a significantly higher incidence of multiorgan dysfunction [OR 3.5 (95% CI 2.0-6.3); p < 0.001] as compared to non-scrub typhus group requiring supportive care. The incidence of altered sensorium [OR 8.8 (95% CI 3.1-24.9)], seizures [OR 3.0 (95% CI 1.1-8.3)], acute respiratory distress syndrome [OR 17.1 (95% CI 2.1-140.1)], acute renal failure (5% vs. 0%), meningitis [OR 6.2 (95% CI 1.2-31.6)], thrombocytopenia [OR 2.8 (95% CI 1.5-5.1)], transaminitis [OR 2.7 (95% CI 1.6-4.8)], requirement of oxygen [OR 17.8 (95% CI 4.0-80.3)], positive pressure support [OR 3.7 (95% CI 1.2-10.5)] and shock requiring inotropes [OR 3.0 (95% CI 1.3-6.7)] was significantly higher in scrub typhus group as compared to the non-scrub typhus group (Table 1). CONCLUSIONS: Pediatric scrub typhus who were hospitalized had severe systemic manifestations when compared to other causes of fever.

Infantile Tremor Syndrome Followed by West Syndrome: Effect or Continuation of Spectrum?

BACKGROUND: Infantile tremor syndrome (ITS) is a nutritional deficiency syndrome, frequently reported from the Indian subcontinent caused by vitamin B12 deficiency. The West syndrome (WS), on the other hand, is a type of epileptic encephalopathy with variable etiology. CASE SERIES: We present a series of five children who presented with symptoms consistent with ITS and received standard intramuscular vitamin B12 therapy to which good response was observed. All these children were readmitted with WS with a time lag varying from 2 to 12 months. Magnetic resonance imaging brain and metabolic screen were within normal limits. Three out of five patients responded well to adrenocorticotropic hormone (ACTH), remaining two required additional drugs. We hypothesize that WS could have developed after ITS due to developmental desynchronization. CONCLUSION: In the Indian scenario, it is particularly important to be aware of appearance of WS after ITS, because of high prevalence of ITS and devastating nature of WS.

Clinical Spectrum and Outcome of Acute Encephalitis Syndrome in Children with Scrub Typhus: A Series of Eight Cases from India.

Scrub typhus has reemerged with a different geographical distribution and varied clinical presentation like acute encephalitis syndrome (AES), which is a less known entity in scrub typhus. In this case series, we studied the clinical profile and outcome of eight patients who presented with AES and a positive scrub serology without any other identifiable cause of encephalopathy. All these patients had fever, altered sensorium, and nuchal rigidity, while seizures were present in six (75%) patients and papilledema in two (25%) patients. Complications like shock, pulmonary edema, and gastrointestinal (GI) bleed were observed in three (37%) patients. All patients except for one responded well to the treatment and recovered completely. Scrub typhus should be suspected early in patients presenting with AES. How to cite this article: Kaur P, Jain R, Kumar P, Randev S, Guglani V. Clinical Spectrum and Outcome of Acute Encephalitis Syndrome in Children with Scrub Typhus: A Series of Eight Cases from India. Indian J Crit Care Med 2020;24(9):885-887.

Patterns in antimicrobial susceptibility of Salmonellae isolated at a tertiary care hospital in northern India.

BACKGROUND & OBJECTIVES: Multidrug-resistant Salmonellae have emerged worldwide as also in India. The aim of this study was to study the antimicrobial susceptibility pattern of Salmonella enterica serovars isolated at a tertiary care hospital in northern India. METHODS: A total of 106 S. enterica serovars isolated from various clinical samples from January 2011 to June 2012 were tested for antimicrobial susceptibility by Kirby-Bauer disk diffusion method. The minimum inhibitory concentration (MIC) of ciprofloxacin, chloramphenicol and ceftriaxone was determined both by agar dilution method and E-test for all the isolates. RESULTS: Salmonella Typhi (73.6%) was the predominant isolate followed by S. Paratyphi A (15.1%), S. Typhimurium (9.4%) and S. Enteritidis (1.9%). Of these, 34 (32.1%) were resistant to ciprofloxacin (MIC ≥1 µg/ml by agar dilution) with MIC90 of ciprofloxacin for S. Typhi, S. Paratyphi A and S. Typhimurium being 32, 4 and 1 µg/ml, respectively. All the isolates were sensitive to chloramphenicol (MIC ≤8 µg/ml) and ceftriaxone (MIC ≤1 µg/ml). Disk diffusion method showed high susceptibility rates to cefotaxime (100%), azithromycin (93.4%) and co-trimoxazole (97.2%). Nalidixic acid resistance was seen in 105 (99.1%) isolates. Of the nalidixic acid-resistant strains, only 34 (32.3%) were found to be resistant to ciprofloxacin (MIC ≥1 µg/ml). INTERPRETATION & CONCLUSIONS: This study showed an alarming increase in MIC to quinolones and re-emergence of susceptibility to conventional antibiotics among Salmonellae.

Accuracy of New Ballard Score in Small-for-gestational Age Neonates.

OBJECTIVE: The aim of this study was to evaluate the performance of New Ballard Score (NBS) in small-for-gestational age (SGA) neonates. METHODOLOGY: Neonates born at 35-40 weeks of gestation were included if accurate obstetric gestation estimate was available and birth weight was <10th percentile for gestation. Gestation-matched appropriate-for-gestational-age neonates were enrolled as controls. Gestation derived from NBS was compared with gestation calculated from last menstrual period. RESULTS: Gestational age estimated by NBS was significantly higher in SGA neonates (mean difference: 0.7 weeks). Neuromuscular component score was similar but physical component score was significantly higher in SGA neonates. Reanalysis after reducing score of 4 to 3 of SGA babies for skin and plantar crease physical parameters showed overestimation of gestational age decreased to 0.4 weeks. CONCLUSIONS: The physical parameters of NBS overestimate gestation in SGA neonates. Changing scores of skin and plantar creases in SGA neonates better estimates gestation age.

Salivary lactate dehydrogenase levels can provide early diagnosis of hypoxic-ischaemic encephalopathy in neonates with birth asphyxia.

AIM: Timely detection of hypoxic-ischaemic encephalopathy (HIE) is crucial for selecting neonates who are likely to benefit from neuroprotective therapy. This study evaluated the efficacy of salivary lactate dehydrogenase (LDH) in the early diagnosis of HIE among neonates with perinatal asphyxia. METHODS: We prospectively enrolled 30 neonates who needed resuscitation at birth or had a history of delayed cry into the HIE group if they developed HIE within 12 h of birth. The control group comprised 30 neonates who had no evidence of HIE, but had intrapartum foetal distress or needed resuscitation at birth. LDH was measured using saliva samples collected within 12 h of birth. RESULTS: Salivary LDH was significantly higher in the HIE group, with a median of 2578 and an interquartile range (IQR) of 1379-3408 international units per litre (IU/L), than in the control group (median 558.5, IQR: 348-924 IU/L, p < 0.001). The test demonstrated excellent discriminating ability: the area under the curve was 0.92 and the levels of 893 IU/L showed a sensitivity of 90% and a specificity of 73.3%. CONCLUSION: Measuring salivary LDH among neonates with birth asphyxia provided an early and accurate diagnosis of HIE and could be used as a triage tool.

Accuracy of transcutaneous bilirubin measurement in preterm low-birth-weight neonates.

UNLABELLED: The objective of this study was to evaluate the correlation and agreement between transcutaneous and serum bilirubin among preterm low-birth-weight neonates. Neonates born at <35 weeks of gestation with birth weight <2,000 g were enrolled prospectively. Transcutaneous bilirubin (TcB) was measured at forehead, sternum, and abdomen at 24 ± 6 and 72 ± 12 h after birth and when icterus involved arms or legs (Kramer zone 4-5). Serum total bilirubin (STB) was measured by microbilimeter (STB-M) at all these time-points and by high-performance liquid chromatography (STB-H) at one randomly chosen time-point. A total of 1,619 observations were made in 256 neonates (median gestation, 34 weeks (IQR, 32-35), birth weight 1,522 ± 288 g). Overall there was excellent correlation and agreement between TcB and STB-M with TcB on forehead being most accurate (r = 0.84, mean difference, 0.3 ± 1.9 mg/dL) followed by TcB on abdomen (r = 0.73, mean difference, 1.5 ± 2.6 mg/dL) and sternum (r = 0.72, mean difference, 1.5 ± 2.6 mg/dL). TcB performed well at all three points of measurement with best correlations being observed at icterus level 4/5. Correlation between TcB and STB-H measured by high-performance liquid chromatography was less strong but significant (r = 0.59 to 0.69 at different time points of measurement). CONCLUSIONS: TcB has good correlation and agreement with STB in preterm low-birth-weight neonates born at ≥28 weeks of gestation.

CLINICAL PROFILE OF EXPANDED DENGUE SYNDROME IN CHILDREN.

The objective is to study the clinical profile and outcome of expanded dengue syndrome (EDS) in children. We conducted a retrospective cohort study and enrolled consecutive children (1 month to 18 years) who presented with dengue fever for over 1 year. The diagnosis of dengue fever was confirmed by the presence of dengue NS1 antigen and/or dengue IgM positivity. Subsequently, we identified children exhibiting EDS according to the revised World Health Organization guidelines (2011). We compared the clinical and laboratory profiles of children diagnosed with EDS and those without EDS. Of 178 children with dengue fever, 33 (18.5%) had EDS [95% confidence interval (CI): 13.1%-25.0%]. In these 33 children, neurological involvement was the most common manifestation [n = 16/33 (49%, 95% CI: 32%-65%)], namely encephalopathy, febrile seizures and encephalitis, respectively. Gastrointestinal involvement was the second most common [n = 10/33 (30%, 95% CI: 17%-47%)], which included fulminant hepatic failure, acalculous cholecystitis and acute pancreatitis. Renal presentation [n = 7 (21%, 95% CI: 10%-37%)] was limited to acute kidney injury. Children with EDS were significantly anemic and had leukocytosis, hyperkalemia, azotemia, hyperbilirubinemia, raised serum transaminases and fluid-refractory shock than their non-EDS counterparts. Children with EDS had a trend toward higher mortality (P = 0.07) and the survivors had a longer duration of hospital stay (5 days vs. 4 days in non-EDS, P = 0.001). In conclusion, we observed a high prevalence (18.5%) of EDS among children hospitalized for dengue fever. The common manifestations of EDS include neurological, renal and gastrointestinal involvement. Children with EDS showed a trend toward higher mortality and longer duration of hospital stay than children without EDS.

Clinical Profile and Outcome of Severe Acute Respiratory Illness (SARI) in Children Amidst the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES:  Beginning in December 2019, COVID-19 rapidly emerged as a global pandemic. Though its severity in children was reported to be less than that in adults, data on its epidemiology in relation to severe acute respiratory illness (SARI) caused by other microbes needed to be generated. This study compares the clinical profile and outcome of children hospitalized with COVID-19-positive and negative SARI. METHODS:  This is a prospective observational analytical study involving children 1 month to 18 years old, hospitalized with COVID-19-positive and negative SARI during the pandemic. All eligible patients were enrolled after obtaining informed parental consent. Their clinical manifestations, investigations, and outcomes were documented on a predesigned case record form. A nasopharyngeal swab sample for COVID-19 reverse transcription polymerase chain reaction was sent, and results were noted. RESULTS:  From May 2020 to July 2021, 267 children were hospitalized with a diagnosis of SARI. Out of these, 146 (54.7%) were boys and 78.7% were under five years of age. Other presentations included fever and cough, breathlessness, nausea, vomiting, diarrhea, rash, seizures, and altered sensorium. Twenty-eight patients (10.5%) tested positive for COVID-19. COVID-19 patients were similar in terms of demographic characteristics and presenting symptoms to non-COVID-19 patients but had a lower absolute lymphocyte count (p = 0.019) and higher serum alanine transaminase levels (p = 0.013). Acute respiratory distress syndrome (OR, 4.3; 95% CI, 1.8-10.0), shock (OR, 3.9; 95% CI, 1.9-7.9), and need for intensive care unit admission (OR, 9.9; 95% CI, 6.9-14) were more common in COVID-19 SARI patients. Death occurred in 18% of COVID-19 and 9% of non-COVID-19 patients (p = 0.07). SARI nonsurvivors had significantly lower blood pH and platelet counts than survivors. CONCLUSIONS: Comparison of COVID-19-positive and negative SARI patients showed subtle differences between the two groups, with COVID-19-positive children having an increased severity of illness. Also, laboratory evidence of multiorgan dysfunction at admission was associated with higher mortality.

Acute demyelinating encephalomyelitis in a child with pulmonary tuberculosis.

Tuberculosis is a leading cause of mortality in children worldwide. One of the greatest challenges in its management is the difficulty of diagnosis as the manifestations are non-specific and often mimic other illnesses. Neurological infection occurs in approximately 1% of patients diagnosed with tuberculosis, and usually takes the form of tuberculous meningitis or tuberculoma. An 11-year-old girl who was diagnosed with acute disseminated encephalomyelitis, a rare immunological manifestation of tuberculosis, is presented. She recovered completely after a course of high-dose systemic corticosteroids in addition to anti-tuberculosis treatment. Considering the immense burden of this infectious disease, recognition and understanding of the uncommon manifestations are important to enable appropriate and timely treatment.Abbreviations: ADEM: acute disseminated encephalomyelitis; ATT: anti-tuberculosis therapy; CBNAAT: cartridge-based nucleic acid amplification test; CNS: central nervous system; CSF: cerebrospinal fluid; CT: computed tomography; FLAIR: fluid attenuated inversion recovery; IFN: interferon; MRI: magnetic resonance imaging; MTB: Mycobacterium tuberculosis; TB: tuberculosis; TNF: tumour necrosis factor.

Neuroimaging Findings in Vitamin B12-Deficient Infants With Neurologic Features.

Background:Vitamin B12 deficiency causes serious neurologic problems among infants. However, its neuroradiologic correlate is still largely obscure. Methodology: This prospective study was conducted on patients aged 6 months to 2 years. All children with proven vitamin B12 deficiency were planned to undergo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy of the brain. Results: A total of 35 patients (63% female) were enrolled. Twenty-six (74%) patients had significant findings on brain MRI scan, commonest of which were thinning of corpus callosum and prominence of extra-axial spaces in 28.6% children, cerebral atrophy in 17%, and diffuse symmetrical hyperintensity of white matter in 5.7% patients. Using logistic regression, it was found that odds of abnormal neuroimaging findings were higher in children below 12 months, in females, and in patients with developmental regression, but none of them were statistically significant. Conclusion: Most of the infants with vitamin B12 deficiency have abnormal neuroimaging findings.

Open-labeled Randomized Controlled Trial on Efficacy of Azithromycin Versus Doxycycline in Pediatric Scrub Typhus.

BACKGROUND: Doxycycline (DX) is the first-line therapeutic agent for scrub typhus. Macrolides, especially azithromycin (AZ), have been found to be equally efficacious as DX for treating scrub typhus in adults. We conducted this study to compare the efficacy of AZ versus DX in pediatric scrub typhus. STUDY DESIGN: Open-label randomized controlled trial. METHODS: Children 1-14 years of age suffering from acute febrile illness of ≥5 days and with a positive scrub IgM serology were randomized to receive either DX (2.2 mg/kg/dose twice daily in <40 kg; 100 mg BD in >40 kg for 7 days) or AZ (10 mg/kg/day for 5 days). The primary outcome was defervescence within 7 days of DX or 5 days of AZ. RESULTS: We had 75 children randomized and analyzed using an intention-to-treat approach and 60 children analyzed via per-protocol analysis. The proportion of children achieving defervescence was comparable in 2 groups [per-protocol analysis: 90.9% in the DX group vs. 96.3% in the AZ group, RR: 0.94 (95% CI: 0.83-1.08)]. On Kaplan-Meier curves, AZ showed a significantly higher probability of defervescence at any time point during treatment as compared with DX (log-rank test P value 0.035). CONCLUSION: AZ and DX had comparable rates of defervescence among children with scrub typhus. Trial registration No.: CTRI/2020/01/022991.