Background: Hyponatremia has frequently been described as a common complication associated with bacterial meningitis, though its frequency and clinical course in children with bacterial meningitis are unclear. The present study aimed to investigate the frequency, clinical characteristics, and prognosis associated with pediatric hyponatremia due to bacterial meningitis. Methods: We performed a retrospective review of children with bacterial meningitis provided with standard care. One hundred seventy-five children were included. We documented all participants' symptoms and signs, laboratory and microbiological data, radiological findings, and complications that occurred during their hospital admission. Disease severity was determined using the maximum Pediatric Cerebral Performance Category (PCPC) and minimum Glasgow Coma Scale (GCS). Residual deficits were assessed using PCPC at discharge. Results: Hyponatremia (<135 mmol/L) was seen in 116 (66.4%) of the patients assessed and was classified as mild (130–135 mmol/L) in 77, moderate (125–129 mmol/L) in 26, and severe (<125 mmol/L) in 13. Hyponatremia was associated with a shorter duration of symptoms before admission, higher CSF white cell counts, and a longer duration of hospitalization. Moderate and severe hyponatremia were associated with an increase in convulsions, impaired consciousness, altered CSF protein levels, higher maximum PCPC scores, and lower minimum GCS scores. Severe hyponatremia was further associated with the development of systemic complications including shock, multiple organ dysfunction syndrome, respiratory failure requiring mechanical ventilation, and an increase in poor outcome (PCPC ≥ 2). Hyponatremia was not associated with the development of neurologic complications. Logistic regression analyses revealed that convulsions (OR 12.09, 95% CI 2.63–56.84) and blood glucose levels > 6.1 mmol/L (OR 8.28, 95% CI 1.65–41.60) predicted severe hyponatremia. Conclusion: Hyponatremia occurred in 66.4% of the assessed pediatric bacterial meningitis patients. Moderate and severe hyponatremia affected the severity of pediatric bacterial meningitis. Only severe hyponatremia affected the short-term prognosis of patients with pediatric bacterial meningitis. We recommend that patients with pediatric bacterial meningitis who exhibit convulsions and increased blood glucose levels should be checked for severe hyponatremia. Further studies are needed to evaluate the effectiveness of treatment of hyponatremia.

Rationale:Pantothenate kinase-associated neurodegeneration (PKAN) represents an autosomal recessive hereditary disease. In this report, a PANK2 gene mutation in a Chinese child was identified, as well as detections of PKAN among his family members. Our findings exposed a world-wide novel compound heterozygous mutation.Patient concerns:We described a 6-year-old male patient with PKAN, exhibiting involuntary movement for a period of 1.5 years, as well as feeding difficulties for 2 weeks.Diagnosis:Due to brain computed tomography and magnetic resonance imaging results, and patient behavior, the attending physician suspected a hereditary effect.Interventions:The patient sample underwent high-throughput sequencing. Subsequently, his parents and sister were screened for the mutations identified in the patient genome.Outcomes:High-throughput sequencing revealed a novel complex heterozygous mutation of the PANK2 gene, which was detected in the second and fourth exons, c.A650G, and c.T1341G, respectively, resulting in amino acid alterations (p.D217G and p.D447E, respectively). The child's father was confirmed to possess a heterozygous c.A650G mutation, while his mother was heterozygous for the c.T1341G mutation.Lessons:The key finding of the study encompassed the detection of a novel PANK2 gene mutation in a child of Chinese ethnicity with PKAN. The PANK2 gene c.A650G, as well as c.T1341G, mutations may be potential mutation hotspots in children with PKAN in Mainland China.

The use of botulinum neurotoxin serotype A (BoNT-A) injections for the treatment of orofacial dyskinesia secondary to anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is rarely reported. Here, we report a case of an urgent, successful management of severe orofacial dyskinesia in an 8-year-old girl with anti-NMDAR encephalitis using BoNT-A injection. The patient presented with de novo unilateral paroxysmal movement disorder progressing to generalized dystonia and repetitive orofacial dyskinesia. Diagnosis was confirmed by the presence of NMDAR antibodies in serum and cerebrospinal fluid. The orofacial dyskinesia worsened despite the aggressive use of first-line immunotherapy and second-line immunotherapy (rituximab), and resulted in a potentially fatal self-inflicted oral injury. We urgently attempted symptomatic management using BoNT-A injections in the masseter, and induced muscle paralysis using vecuronium. The patient’s severe orofacial dyskinesia was controlled. We observed the effects of the BoNT-A injections and a tapering off of the effects of vecuronium 10 days after the treatment. The movement disorder had improved significantly 4 weeks after the first administration of rituximab. The injection of BoNT-A into the masseter may be an effective treatment for medically refractory orofacial dyskinesia in pediatric patients with anti-NMDAR encephalitis. We propose that the use of BoNT-A injections should be considered early to avoid self-inflicted oral injury due to severe refractory orofacial dyskinesia in patients with anti-NMDAR encephalitis.

A series of neurological manifestations such as intellectual disability and epilepsy are closely related to hypomagnesemia. Cyclin M2 (CNNM2) proteins, as a member of magnesium (Mg2+) transporters, were found along the basolateral membrane of distal renal tubules and involved in the reabsorption of Mg2+. Homozygous and heterozygous variants in CNNM2 reported so far were responsible for a variable degree of hypomagnesemia, several of which also showed varying degrees of neurological phenotypes such as intellectual disability and epilepsy. Here, we report a de novo heterozygous CNNM2 variant (c.2228C &gt; T, p.Ser743Phe) in a Chinese patient, which is the variant located in the cyclic nucleotide monophosphate-binding homology (CNBH) domain of CNNM2 proteins. The patient presented with mild intellectual disability and refractory epilepsy but without hypomagnesemia. Thus, we reviewed the literature and analyzed the phenotypes related to CNNM2 variants, and then concluded that the number of variant alleles and the changed protein domains correlates with the severity of the disease, and speculated that the CNBH domain of CNNM2 possibly plays a limited role in Mg2+ transport but a significant role in brain development. Furthermore, it can be speculated that neurological phenotypes such as intellectual disability and seizures can be purely caused by CNNM2 variants.

Rationale:The respective involvements of both the thalamus and exhibitionism in cerebral X-linked adrenoleukodystrophy (X-ALD) have not been reported.Patient concerns:An 11-year-old boy initially presented with exhibitionism and progressive neurobehavioral symptoms. He subsequently developed transient urinary and fecal incontinence, and an unwillingness to eat or communicate.Diagnoses:We conducted contrast-enhanced brain magnetic resonance imaging (MRI), which revealed symmetrical altered signal intensities in bilateral frontal white matter, the basal ganglia, and dorsal thalami, as well as a peripheral rim of contrast enhancement. Diagnosis of adolescent cerebral X-ALD was confirmed on the basis of next generation genetic sequencing analysis.Interventions:We initiated the patient on hormonal replacement therapy.Outcomes:We observed rapidly progressive neurologic deterioration in this patient, and the boy fell into a vegetative state 10 months after discharge.Lessons:We recommend that physicians should not disregard X-ALD in patients with isolated psychiatric symptoms, including hypersexual behavior. The combination of detailed clinical evaluation, MRI, and next generation genetic sequencing can expedite the diagnostic process of atypical variant of X-ALD.

The blood−brain barrier (BBB) is an important physiological barrier of the human body contributing to maintaining brain homeostasis and normal function. Hypoxic-ischemic (HI)-related brain injury is one of the main causes of neonatal acute morbidity and chronic disability. The previous research of our group confirmed that there was serious BBB destruction during HI brain injury. However, at present, the protection strategy of BBB is very limited, and further research on the protection mechanism is warranted. Indole-3-propionic acid (IPA) is a bacterial metabolism with anti-inflammatory and antioxidant properties, having neuroprotective effects and protective effects on the mucosal barrier. However, the role of IPA in BBB is not clear. In this research, we demonstrated the protective effect of IPA on BBB disruption from HI brain injury and hypothesized that it involves the amelioration of inflammation, oxidative stress, and MMP activation, thereby inhibiting apoptosis of rat brain microvascular endothelial cells (rBMECs). We demonstrated that expression levels of several inflammatory markers, including iNOS, TNF-α, IL-6, and IL-1β, were significantly increased from HI damage or OGD injury. However, IPA treatment inhibited the increase significantly. Moreover, we demonstrated that IPA reduced intracellular ROS levels and MMP activation in rBMECs from OGD injury. Further research on the underlying detailed molecular mechanisms suggested that IPA attenuates inflammation by inhibiting NF-κB signaling. Finally, we investigated the mechanism of the relationship between PXR activation and NF-κB inhibition. The results suggested overexpression of PXR in rBMECs could significantly counteract the decrease of junction proteins and downregulate the increased p-IκB-α and p-NF-κB from OGD injury. However, the protective effects of IPA were reversed by antagonists of the PXR. Taken together, IPA might mitigate HI-induced damage of the BBB and the protective effect may be exerted through modulating the PXR signaling pathway.

Cerebral adrenoleukodystrophy (CALD) is a fatal genetic disease characterized by rapid, devastating neurological decline, with a narrow curative treatment window in the early stage. Non-canonical splice-site (NCSS) variants can easily be missed during genomic DNA analyses, and only a few of them in ABCD1 have been explored. Here, we studied a Chinese patient with clinical features similar to those of early-stage CALD but with a negative molecular diagnosis and a sibling who had presumably died of CALD. Trio-based whole-exome sequencing (trio-WES) and RNA sequencing (RNA-Seq) revealed a novel hemizygote NCSS variant c.901-25_901-9 del in ABCD1 intron 1, resulting in a complex splicing pattern. The in vitro minigene assay revealed that the c.901-25_901-9 del construct contained two aberrant transcripts that caused skipping of exon 2 and a small 48-bp deletion on left of the same exon. We identified a novel NCSS variant, that extends the spectrum of the known ABCD1 variants, and demonstrated the pathogenicity of this gene variant. Our findings highlight the importance of combining RNA-Seq and WES techniques for prompt diagnosis of leukodystrophy with NCSS variants.

PurposeFew studies have evaluated hyponatremia management in children with bacterial meningitis (BM). Thus, we aimed to describe variations in clinical practice, the effectiveness of sodium management, and adverse outcomes in children with BM and hyponatremia.MethodsThis retrospective cross-sectional study conducted at a tertiary institution analyzed participants' demographic, clinical, and sodium-altering treatment data. The sodium trigger for treatment was defined as pretreatment sodium level, with response and overcorrection defined as increments of ≥5 and &gt;10 mmol/L after 24 h, respectively.ResultsThis study enrolled 364 children with BM (age: &lt;16 years; 215 boys). Hyponatremia occurred in 62.1% of patients, among whom 25.7% received sodium-altering therapies; 91.4% of those individuals had moderate/severe hyponatremia. Monotherapy was the most common initial hyponatremia treatment. After 24 h of treatment initiation, 82.4% of the patients responded. Logistic regression analyses revealed that ΔNa24 &lt;5 mmol/L [odds ratio (OR) 15.52, 95% CI 1.71–141.06, p = 0.015] and minimum Glasgow Coma Scale (GCS) score ≤ 8 (OR 11.09, 95% CI 1.16–105.73, p = 0.036) predicted dysnatremia at 48 h after treatment initiation. Although rare, persistent moderate/severe hyponatremia or hypernatremia at 48 h after treatment initiation was associated with a high mortality rate (57.1%).ConclusionThis study found that most cases of hyponatremia responded well to various treatments. It is important to identify and institute appropriate treatment early for moderate or severe hyponatremia or hypernatremia in children with BM. This study was limited by its non-randomized nature.