Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS.

Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40-50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.

Ictal Hypersalivation and Salivary Gland Enlargement in a Patient With Acquired Frontal Lobe Epilepsy.

Hypersalivation is a well-known ictal semiology of benign Rolandic epilepsy and other childhood epilepsy syndromes. There are also occasional reports of adults with temporal, parietal, or frontal lobe epilepsy in which hypersalivation is a prominent seizure manifestation. Notably lacking are reports linking salivary gland enlargement to ictal hypersalivation. A 33-year-old man with frontal lobe epilepsy due to a ruptured aneurysm presented with focal seizures and facial swelling. The only seizures he had in the past were generalized tonic-clonic seizures. Eight days prior to admission, he started having focal seizures characterized by pronounced hypersalivation, speech arrest, impaired awareness, and left upper extremity posturing or automatism. Seizure frequency increased from five to 30 per day. Four days prior to admission, his face started to swell up, and his family thought he had mumps. Computed tomography (CT) of the head showed encephalomalacia in the inferomedial cortex of the right frontal lobe, the same lesion seen in his old CT images. Maxillofacial CT revealed enlargement of the parotid and submandibular glands. Although electroencephalography (EEG) showed seizure onset in the right frontal region, the initial ictal discharge on the scalp may represent seizure propagation from a focus near the zone of encephalomalacia. After seizure freedom was achieved with antiepileptic drugs, the patient's salivary glands decreased in size and returned to normal.

Effects of Simulation Video on Parental Recall of Seizure First Aid: A Quality Improvement Project.

Many parents of children do not recall anticipatory guidance on acute seizure management, which can lead to unnecessary emergency department visits. This quality improvement project evaluated if adding a video simulation of seizure first aid improved parental recall. Parents of children with seizures were randomized to standard verbal counseling or video group, which were shown a video simulation of seizure first aid. All families also received a standardized written action plan. Eighty-three patients were randomized from July to October 2018. Overall, 53% of families who received standard counseling accurately recalled seizure first aid compared with 31% in video group (χ2 = 3.24, P = .07). Among families without baseline knowledge of seizure first aid, 43% in the standard counseling group recalled accurately compared with 16% of video group (χ2 = 4.52, P = .03). These results underscore the importance of face-to-face patient education despite the popularity of video-based media. Future Plan-Do-Study-Act cycles will include piloting a hands-on seizure first aid simulation with mannequins.

Focal Epileptiform Discharges Can Mimic Electrode Artifacts When Recorded on the Scalp Near a Skull Defect.

Breach rhythm, the hallmark of skull defect, is a familiar finding in the electroencephalogram (EEG). A hole in the skull can also give rise to unfamiliar EEG findings. We present 3 patients with a skull defect whose scalp EEG showed focal epileptiform discharges that resembled F4 electrode artifacts-a 23-year-old man with a right-sided craniectomy for traumatic brain injury, a 63-year-old woman with a history of bifrontal craniectomy and meningioma resection, and a 77-year-old woman who had a right hemicraniectomy for a life-threatening subdural hematoma. In all 3 patients, the F4 electrode was directly above or near a skull defect, and scalp EEG showed phase-reversing waves in FP2-F4 and F4-C4 with no clear-cut "physiological field" (even when the EEG was displayed at a higher sensitivity). In the first 2 patients, the technologist tried to eliminate the "electrode artifacts" by cleaning the scalp thoroughly, replacing the F4 electrode, and maintaining electrode impedance between 2 and 5 kΩ. These measures failed to eliminate the "electrode artifacts" so the EEG was recorded from four 10-10 electrode sites around F4. Extending the montage made it clear that what appeared as F4 electrode artifacts were actually focal epileptiform discharges. Correlation with other electroclinical and neuroimaging data was enough to resolve this issue in the third patient, obviating the need to extend the montage. When recording and interpreting the EEG of patients with a craniotomy or craniectomy, EEG professionals should be aware that focal epileptiform discharges can masquerade as electrode artifacts.

Treatment considerations for recurrent MRSA bacteremia leading to cholecystitis.

We present an end-stage renal disease patient with acute cholecystitis caused by a recurrence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Timely antibiotic therapy with vancomycin did not eradicate the patient's infection. In this patient, the minimum inhibitory concentration (MIC) of the organism for vancomycin was at the upper limit of susceptibility. The ability to thoroughly understand and interpret mean inhibitory concentrations is crucial in antibiotic selection. For high-risk patients with Staphylococcus aureus infection with reduced susceptibility to vancomycin as demonstrated by an MIC of 2 mg/L or greater, we suggest further investigation into linezolid as an alternative antibiotic to vancomycin therapy. Compared to vancomycin, linezolid has similar effectiveness in patients with MRSA bacteremia as well as improved penetration, particularly in bile.

Radiology case of the month. An unusual case of hemorrhage with rapid deterioation. Posterior reversible encephalopathy syndrome (PRES).

A 42-year-old female presented to the emergency room with altered mental status and visual disturbances. Patient has a known history of recent liver transplant and currently takes cyclosporine. Patient underwent multimodality imaging, including CT and MRI and suffered rapid deterioration within 24 hours.