Increasing Seizures, Encephalopathy, and Hypothermia in an 18-Year-Old Woman.

ABSTRACT: An 18-year-old woman with a history of focal epilepsy presents with increasingly frequent seizures, encephalopathy, multiple laboratory abnormalities, and hypothermia. During her hospital course, her symptoms waxed and waned. Multiple etiologies of her symptoms were considered, but the spontaneous resolution of her symptoms and an abnormal MRI of the brain revealed the final diagnosis.

Electrodiagnostic Findings in Riboflavin Transporter Deficiency Type 2.

ABSTRACT: We present the electrodiagnostic findings in a case of a 3-year-old girl presenting with sensory ataxia, gait disturbance, and visual-auditory disturbance with a genetically confirmed diagnosis of riboflavin transporter deficiency type 2 (RTD2). She carries a homozygous mutation in the SLC52A2 gene, c.1016T>C (p.Leu339Pro). Her testing demonstrates a non-length-dependent axonal sensorimotor polyneuropathy affecting predominantly the upper extremities with active denervation of the distal muscles of both arms. It is important to highlight these findings because most genetic neuropathies have a length-dependent pattern of involvement, affecting the distal legs before the arms. The electrodiagnostic findings in RTD2 have not been previously well described. These electrodiagnostic findings are in agreement with the typical clinical phenotype of RTD2, which affects the upper limbs and bulbar muscles more than the lower extremities.

Institutional Pediatric Convulsive Status Epilepticus Protocol Decreases Time to First and Second Line Anti-Seizure Medication Administration.

PURPOSE: Convulsive status epilepticus (CSE) is a medical emergency associated with high rates of morbidity and mortality. Although guidelines for CSE management recommend rapid treatment of seizures, prior studies show that compliance with these guidelines is low. In this study, we assessed if implementation of a paper-based clinical pathway for the treatment of CSE improves the timeliness and appropriate dosing of first and second line anti-seizure medications (ASM). METHODS: A non-digital CSE treatment protocol was implemented as part of a quality improvement initiative in 2016. A retrospective analysis was subsequently conducted on cases of CSE originating in the pediatric emergency department (ED) from 2012-2019. Standard descriptive statistics were used to assess patient demographics as well as the timing and dosing of the first and second line ASMs used in our protocol (lorazepam [LZP] and fosphenytoin [FOS]). Statistical process control charts (XmR charts) were used to assess the variation in time to drug administration before and after implementation of the protocol. RESULTS: 153 cases of CSE were identified (72 prior to and 81 after protocol implementation). Among patients who were actively having seizures on arrival to the ED (n = 44), the median time from arrival to ASM administration decreased from 15 to 11 minutes for the first LZP dose (p = 0.23), 23 to 10 minutes for the second LZP dose (p = 0.06), and 40 to 25 minutes for the PHE dose (p = 0.04). There was no improvement in time to LZP administration after seizure onset among those with seizure onset after hospital arrival (5 minutes before/after implementation for the first LZP dose and 15 to 14 minutes for second LZP dose); however, the time to FOS decreased from 42 to 22 minutes (p = 0.86). Statistical process control charts showed a universal decrease in variation for time to each drug administration after protocol implementation. Whereas FOS dosing was largely appropriate before and after protocol implementation, appropriate dosing of LZP did not improve, with only about half of patients receiving the recommended dose. CONCLUSION: The implementation of a paper-based treatment protocol for CSE was associated with a decreased time to ASM administration among patients who arrived to the ED, particularly for the second-line ASM. Approaches for improving appropriate benzodiazepine dosing are needed.

Child Neurology: A young child with an undiagnosed case of dystonia responsive to l-dopa.

Childhood-onset dystonias are a heterogeneously diverse group. There exists a specific set of dystonias that respond profoundly well to low doses of l-dopa (dopa-responsive dystonia [DRD]). Classical DRD is caused by deficiency of GTP cyclohydrolase 1 or tyrosine hydroxylase, but other conditions can cause dystonias that are partially responsive to dopamine. The idea of a diagnostic therapeutic trial with l-dopa for children who present with dystonia has been around for decades and is frequently advocated for; however, l-dopa trials are not without risk.

Respiratory syncytial virus G protein CX3C motif impairs human airway epithelial and immune cell responses.

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory infection in infants and young children and causes disease in the elderly and persons with compromised cardiac, pulmonary, or immune systems. Despite the high morbidity rates of RSV infection, no highly effective treatment or vaccine is yet available. The RSV G protein is an important contributor to the disease process. A conserved CX3C chemokine-like motif in G likely contributes to the pathogenesis of disease. Through this motif, G protein binds to CX3CR1 present on various immune cells and affects immune responses to RSV, as has been shown in the mouse model of RSV infection. However, very little is known of the role of RSV CX3C-CX3CR1 interactions in human disease. In this study, we use an in vitro model of human RSV infection comprised of human peripheral blood mononuclear cells (PBMCs) separated by a permeable membrane from human airway epithelial cells (A549) infected with RSV with either an intact CX3C motif (CX3C) or a mutated motif (CX4C). We show that the CX4C virus induces higher levels of type I/III interferon (IFN) in A549 cells, increased IFN-α and tumor necrosis factor alpha (TNF-α) production by human plasmacytoid dendritic cells (pDCs) and monocytes, and increased IFN-γ production in effector/memory T cell subpopulations. Treatment of CX3C virus-infected cells with the F(ab')2 form of an anti-G monoclonal antibody (MAb) that blocks binding to CX3CR1 gave results similar to those with the CX4C virus. Our data suggest that the RSV G protein CX3C motif impairs innate and adaptive human immune responses and may be important to vaccine and antiviral drug development.