SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

Human TMEFF1 is a restriction factor for herpes simplex virus in the brain.

Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR-Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.

Double-Bending Tension Band Wire for Olecranon Fractures: A Novel Technique.

Purpose: This retrospective study aimed to compare the clinical outcomes and complications of conventional tension band wire (TBW), TBW with penetrating technique, and double-bending technique. Methods: A total of 40 patients (17 men and 23 women; mean age: 64.0 ± 19.0 years) who underwent surgery for displaced olecranon fractures between January 2018 and December 2021 were included and divided into three groups based on the surgical method used (group A, conventional TBW; group B, TBW with penetrating technique; and group C, double-bending technique). Thirteen patients were assigned to group A, 17 to group B, and 10 to group C, including 2 Mayo type IB, 30 Mayo type IIA, and 8 Mayo type IIB fractures. Postoperative outcomes (elbow extension and flexion arc) and complications, such as backing out of the Kirschner wire (K-wire), were retrospectively evaluated. Results: No significant difference was found in the general characteristics of the patients and fracture type among the three groups. The mean elbow extension arc values were 6.2°, 10.9°, and 0° in groups A, B, and C, respectively; it was significantly better in group C than in group B (P = .001). The rates of backing out of the K-wire were 84.6% (11/13) in group A, 41.2% (7/17) in group B, and 0% (0/10) in group C; the rate was significantly lower in group C than in group A (P < .001). Conclusions: The double-bending technique may be the best procedure for preventing the backing out of the K-wire and postoperative complications, such as range of motion restriction, for treating olecranon fractures that are treatable by TBW. Type of study/level of evidence: Therapeutic IV.

Postoperative Complications of Surgery for Cervical Spondylotic Myelopathy with and Without Athetoid Cerebral Palsy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: With the aging of the Japanese population, patients with athetoid cerebral palsy (ACP) are getting older, and the rate of surgery for CSM is increasing in ACP patients. However, postoperative complications of such surgery among adult patients with ACP have not been reported yet. We investigated postoperative complications of surgery for CSM with ACP and compared them with those of surgery for CSM without ACP using a national inpatient database of Japan. METHODS: Using the Diagnosis Procedure Combination database, we identified 61382 patients who underwent surgery for CSM from July 2010 to March 2018. We examined patient backgrounds, surgical procedures, and type of hospital, and a 4:1 propensity score matching was performed to compare the outcomes between the non-ACP and ACP groups. RESULTS: There were 60 847 patients without ACP and 535 patients with ACP. The mean age was 68.5 years in the non-ACP group and 55 years in the ACP group. The percentages of patients who underwent fusion surgery were 21.6% and 68.8% in the non-ACP and ACP groups, respectively. The 4:1 propensity score matching selected 1858 in the non-ACP group and 465 in the ACP group. The ACP group was more likely to have postoperative urinary tract infection (.4% vs 2.8%, P < .001), postoperative pneumonia (.4% vs 2.4%, P < .001), and 90-day readmission for reoperation (1.9% vs 4.3%, P = .003). CONCLUSIONS: We found that ACP patients were more vulnerable to postoperative complications and reoperation after CSM than non-ACP patients.

Diurnal Variation of Brain Activity in the Human Suprachiasmatic Nucleus.

The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, we localized the SCN by employing an areal boundary mapping technique to resting-state functional images and investigated the SCN activity using perfusion imaging. In the first experiment (n = 27, including both sexes), we scanned each participant four times a day, every 6 h. Higher activity was observed at noon, while lower activity was recorded in the early morning. In the second experiment (n = 20, including both sexes), the SCN activity was measured every 30 min for 6 h from midnight to dawn. The results showed that the SCN activity gradually decreased and was not associated with the electroencephalography. Furthermore, the SCN activity was compatible with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of nocturnal and diurnal mammals and is modulated by physical lights rather than the local time.

Patients with a large ossification of the posterior longitudinal ligament have a higher incidence of arteriosclerosis in the carotid artery.

PURPOSE: This study aimed to investigate the impact of the severity of cervical ossification of the posterior longitudinal ligament (OPLL) on the incidence of arteriosclerosis in the carotid artery. METHODS: Patients with OPLL-induced cervical myelopathy were prospectively enrolled. The study involved analyzing patient characteristics, blood samples, computed tomography scans of the spine, and intima-media thickness (IMT) measurements of the common carotid artery. Patients were divided into two groups based on the size of the cervical OPLL to compare demographic data, comorbidities, and the presence of thickening of the carotid intima-media (max IMT ≥ 1.1 mm). RESULTS: The study included 96 patients (mean age: 63.5 years; mean body mass index: 26.9 kg/m2; 71.8% male; 35.4% with diabetes mellitus). The mean maximum anteroposterior (AP) diameter of the OPLL was 4.9 mm, with a mean occupancy ratio of 43%. The mean maximum IMT was 1.23 mm. Arteriosclerosis of the carotid artery was diagnosed in 62.5% of the patients. On comparing the two groups based on OPLL size, the group with larger OPLL (≥ 5 mm) had a higher BMI and a greater prevalence of carotid intima-media thickening. This significant difference in the prevalence of carotid intima-media thickening persisted even after adjusting for patient backgrounds using propensity score matching. CONCLUSIONS: Patients with a larger cervical OPLL showed a higher frequency of intima-media thickening in the carotid artery.