Encephalitis in Thailand: A Neglected Disease Increasingly Caused by Enterovirus

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

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

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

Lack of Transmission of Zika Virus Infection to Breastfed Infant

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

Hand knob sign in osmotic demyelinating syndrome

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

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

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