Utility of Film Array Meningoencephalitis Panel in Children With Acute Encephalitis Syndrome: A Single Centre Experience from South India.

OBJECTIVE: To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES). METHODS: A retrospective audit was conducted between January 2017 to July 2022. We included children aged < 18 years with a diagnosis of AES for whom a CSF analysis study including FAME panel testing performed within 48 hours of admission was available. Electronic medical records were reviewed for details including demographic profile, clinical presentation, investigations and outcome. RESULTS: Out of 157 CSF samples sent for FAME panel testing, 49 were positive (31.4%.) Viral pathogens were identified in 42 (Enterovirus: 31, Human herpes virus 6: 9, Varicella zoster virus: 1, and Cytomegalovirus: 1) Bacterial pathogens were identified in 6 (Streptococcus pneumoniae: 2, Streptococcus agalactiae: 2, Hemophilus influenzae: 1, and Escherischia coli: 1). Fungal etiology (Cryptococcus neoformans) was detected in one child. Antibiotics could be stopped within 72 hours of initiation in 42 children in whom a viral etiology was established. Acyclovir could be stopped in 21 out of 32 children within 72 hours after the FAME panel testing. FAME panel was presumed to be false positive in 4 children. CONCLUSION: Etiology of AES could be established in nearly a third of children with AES using the rapid diagnostic FAME panel testing in CSF and it was found to be effective in reducing empirical antibiotic/antiviral therapy.

Comparison of 4 weeks versus 12 weeks antiseizure medication for acute symptomatic seizures in children with Acute Encephalitis Syndrome: An open-label, randomized controlled trial.

OBJECTIVE: To compare the proportion of children with seizure recurrence/s during 6-18 months of follow-up among children with acute symptomatic seizures underlying acute encephalitis syndrome (AES) treated with either 4 weeks or 12 weeks of antiseizure medication (ASM). METHODS: Eligible children aged 3 months to 12 years with acute symptomatic seizures underlying AES, receiving a single ASM at 4 weeks of illness, and without seizure recurrence from day 7-28 of illness were included in this comparative, parallel-group assignment, open-label, randomized control study (either 4 weeks or 12 weeks duration). The primary outcome was to compare proportions of children developing seizure recurrence over six months of follow-up. The secondary outcomes were to study seizure recurrence over 12-18 months follow-up and factor(s) associated with seizure recurrence. RESULTS: Of 232 children with AES screened, 60 eligible children were randomized in two groups. Baseline demographics were comparable (except the duration of illness) between the groups. Seizure recurrences at 6, 12 and 18 months were none, two (one in each group, relative risk 1.0, 95% CI 0.06-16.76; p-value >0.99), and six (one and five children in 4 and 12 weeks groups respectively, relative risk 0.17, 95% CI 0.01-1.62; p-value 0.19) respectively. There was no association of seizure recurrences with seizure characteristics, abnormal electroencephalography and neuroradiology. Children with disabilities at randomization had a higher risk of seizure recurrence at 18 months of follow-up (relative risk 7.16, 95% CI 1.1-43.9; p-value 0.049). SIGNIFICANCE: With limitations of the study design, this study provides Class I evidence that a shorter duration (4 weeks) of ASM is comparable with 12 weeks therapy for preventing seizure recurrences in children with AES. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT03181945; Clinical Trial Registry of India identifier: CTRI/2017/06/008783.

Effectiveness of Homeopathic Medicines as Add-on to Institutional Management Protocol for Acute Encephalitis Syndrome in Children: An Open-Label Randomized Placebo-Controlled Trial.

BACKGROUND: Acute encephalitis syndrome (AES) is endemic to certain parts of India, with limited treatment options. In our initial exploratory comparative observational study of 151 patients with AES, there was significantly reduced mortality with adjunctive homeopathy compared to institutional management protocol (IMP). The present randomized placebo-controlled trial brings more statistical rigor to this research program. METHODS: This study was conducted at a pediatric unit from 2013 to 2015. Children aged > 6 months and ≤ 18 years and receiving IMP were randomized to receive adjunctive homeopathy (n = 325) or placebo as control (n = 323). The primary effectiveness analysis was based on Glasgow Outcome Scale (GOS). Morbidity was assessed using the Liverpool Outcome Score for Assessing Children at Follow-up. Analysis was by intention to treat. RESULTS: A total of 612 children were analyzed (Homeopathy [H] = 304; Control [C] = 308). The primary outcome, GOS, differed significantly between H and C groups. There was 14.8% death/neuro-vegetative state in the H group compared to 29.8% in the C group. Relative risk was 0.49 (95% confidence interval [CI]: 0.36 to 0.68), with absolute risk reduction of 15.0% (95% CI: 8.6 to 21.6%). Number needed to treat to prevent one additional death/neuro-vegetative state was 6.6 (95% CI: 4.6 to 11.6). Proportional-odds analysis also revealed a greater effect in the H group: odds ratio, 0.40 (95% CI: 0.27 to 0.60). The most frequently used medicines were Belladonna (n = 116), Stramonium (n = 33), Arsenicum album (n = 25), Sulfur (n = 18), Opium (n = 17), and Nux vomica (n = 10). CONCLUSION: Adjunctive homeopathic medicines may improve clinical outcomes associated with AES. Further randomized and controlled studies, using double-blinded trial design, are recommended to discover if the current findings may be corroborated.

Prognostic factors in the early phase of acute encephalopathy.

BACKGROUND: Neurological sequelae occur in 40% of patients with acute encephalopathy (AE). The early prediction of poor outcomes is critical to the initiation of appropriate treatment. The aim of the present study was therefore to elucidate prognostic factors that can be quickly and feasibly evaluated on hospital admission in patients with AE. METHODS: We analyzed data from 51 AE patients admitted to Hirakata City Hospital between January 2005 and December 2014. Age at onset, sex, underlying disease, status epilepticus (SE), presence of benzodiazepine-resistant SE (BZD-resistant SE), and basic blood serum parameters on admission were evaluated in relation to each patient's outcome. RESULTS: On univariate analysis age at onset, BZD-resistant SE, and serum aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and platelet count varied significantly according to outcome. On multivariate analysis age at onset (≤21 months), presence of BZD-resistant SE, and AST (≥46 IU/L) were identified as independent variables associated with poor outcome. CONCLUSION: Age at onset, presence of BZD-resistant SE, and AST are associated with a poor prognosis in AE.

Clinical Predictors of Malaria, Acute Bacterial Meningitis and Treatment Outcomes among Febrile Children Admitted with Altered Mental Status in Northwestern Tanzania.

Background: Malaria and acute bacterial meningitis (ABM) are the leading infectious causes of febrile encephalopathy in malaria endemic settings. The clinical distinction of the two conditions is complicated by overlap in clinical features. Objective: To determine the clinical predictors for malaria, ABM and treatment outcome in febrile children aged 2 months to 12 years with altered mentation at two tertiary hospitals in Northwestern Tanzania. Methods: Prospective study of 103 children to document demographic data and physical examination findings, such as level of consciousness and meningeal irritations. Laboratory results for cerebrospinal fluid, hemoglobin, malaria and HIV were also evaluated. Results: Age >60 months and hemoglobin ≤5 g/dl were independent predictors of malaria; (p = 0.013 and 0.004, respectively). HIV infection was the only predictor of meningitis, p = 0.037, and mortality was high if the diagnosis was unconfirmed. Conclusions: Children with febrile encephalopathy are more likely to have malaria than ABM if they have severe anemia.

Serotonin syndrome presenting as febrile encephalopathy with CSF pleocytosis: a report of three cases.

Serotonin syndrome (SS) is an iatrogenic, drug-induced clinical syndrome caused by serotoninergic hyperstimulation. SS may have protean manifestations and can mimic a variety of medical conditions. Herein, we describe three cases of febrile encephalopathy who were on serotonergic agents. All three cases fulfilled Hunter's criteria for SS and responded to the removal of the offending agents and the administration of cyproheptadine. All three patients had abnormal cerebrospinal fluid (CSF) examinations (pleocytosis in three patients and increased protein in two patients) which returned to normal with therapy. We suggest that SS presenting as febrile encephalopathy may have transient CSF abnormalities. Severe SS is a medical emergency. Therefore, a trial of cyproheptadine can be given in patients fulfilling the SS criteria even in the presence of CSF abnormalities. In parallel, the patients should be investigated for other causes of febrile encephalopathy and CSF pleocytosis.