Lithium Provides Broad Therapeutic Benefits in an Alzheimer's Disease Mouse Model.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disorder with a progressive loss of cognitive function. Currently, no effective treatment regimen is available. Lithium, a mood stabilizer for bipolar disorder, exerts broad neuroprotective and neurotrophic actions and improves cognitive function. OBJECTIVE: The study investigated if lithium stabilizes Ca2+ signaling abnormalities in hippocampal neurons and subsequently normalize downstream effects on AD neuropathology and synaptic plasticity in young AD mice. METHODS: Four-month-old 3xTg-AD mice were treated with a LiCl diet chow for 30 days. At the end of the lithium treatment, a combination of two-photon Ca2+ imaging, electrophysiology, and immunohistochemistry assays were used to assess the effects of the LiCl treatment on inositol trisphosphate receptor (IP3R)-dependent endoplasmic reticulum (ER) Ca2+ and voltage-gated Ca2+ channel (VGCC)-mediated Ca2+ signaling in CA1 neurons, neuronal nitric oxide synthase (nNOS) and hyperphosphorylated tau (p-tau) levels and synaptic plasticity in the hippocampus and overlying cortex from 3xTg-ADmice. RESULTS: Thirty-day LiCl treatment reduced aberrant IP3R-dependent ER Ca2+ and VGCC-mediated Ca2+ signaling in CA1 pyramidal neurons from 3xTg-AD mice and restored neuronal nitric oxide synthase (nNOS) and hyperphosphorylated tau (p-tau) levels to control levels in the hippocampal subfields and overlying cortex. The LiCl treatment enhanced post-tetanic potentiation (PTP), a form of short-term plasticity in the hippocampus. CONCLUSION: The study found that lithium exerts therapeutic effects across several AD-associated early neuronal signaling abnormalities including aberrant Ca2+ signaling, nNOS, and p-tau formation and enhances short-term synaptic plasticity. Lithium could serve as an effective treatment or co-therapeutic for AD.

Sport participation and related head injuries following craniosynostosis correction: a survey study.

OBJECTIVE: Craniosynostosis (CS) affects about 1 in 2500 infants and is predominantly treated by surgical intervention in infancy. Later in childhood, many of these children wish to participate in sports. However, the safety of participation is largely anecdotal and based on surgeon experience. The objective of this survey study was to describe sport participation and sport-related head injury in CS patients. METHODS: A 16-question survey related to child/parent demographics, CS surgery history, sport history, and sport-induced head injury history was made available to patients/parents in the United States through a series of synostosis organization listservs, as well as synostosis-focused Facebook groups, between October 2019 and June 2020. Sports were categorized based on the American Academy of Pediatrics groupings. Pearson's chi-square test, Fisher's exact test, and the independent-samples t-test were used in the analysis. RESULTS: Overall, 187 CS patients were described as 63% male, 89% White, and 88% non-Hispanic, and 89% underwent surgery at 1 year or younger. The majority (74%) had participated in sports starting at an average age of 5 years (SD 2.2). Of those participating in sports, contact/collision sport participation was most common (77%), and 71% participated in multiple sports. Those that played sports were less frequently Hispanic (2.2% vs 22.9%, p < 0.001) and more frequently had undergone a second surgery (44% vs 25%, p = 0.021). Only 9 of 139 (6.5%) sport-participating CS patients suffered head injuries; 6 (67%) were concussions and the remaining 3 were nondescript but did not mention any surgical needs. CONCLUSIONS: In this nationwide survey of postsurgical CS patients and parents, sport participation was exceedingly common, with contact sports being the most common sport category. Few head injuries (mostly concussions) were reported as related to sport participation. Although this is a selective sample of CS patients, the initial data suggest that sport participation, even in contact sports, and typically beginning a few years after CS correction, is safe and commonplace.

Deformational brachycephaly: the clinical utility of the cranial index.

OBJECTIVE: The incidence of deformational brachycephaly has risen since the "Back to Sleep" movement in 1992 by the American Academy of Pediatrics. Brachycephaly prevalence and understanding the dynamic nature of the pediatric skull have not been explored in relation to the cranial index (CI). The objective of the study was to determine the prevalence of brachycephaly, via the CI, with respect to time. METHODS: The authors conducted a retrospective review of 1499 patients ≤ 19 years of age who presented for trauma evaluation with a negative CT scan for trauma (absence of bleed) in 2018. The CI was calculated using CT at the lateral-most point of the parietal bone (cephalic width), and the distance from the glabella to the opisthocranion (cephalic length). Brachycephaly was defined as a CI ≥ 90%. RESULTS: The mean CI was 82.6, with an average patient age of 6.8 years. The prevalence of deformational brachycephaly steadily decreased from 27% to 4% from birth to > 2 years of life. The mean CI was statistically different between ages < 12 months, 12-24 months, and > 24 months (F[2,1496] = 124.058, p < 0.0005). A simple linear regression was calculated to predict the CI based on age; the CI was found to decrease by 0.038 each month. A significant regression equation was found (F[1,1497] = 296.846, p < 0.0005), with an R2 of 0.140. CONCLUSIONS: The incidence of deformational brachycephaly is common in infants but decreases as the child progresses through early childhood. Clinicians can expect a significant decrease in mean CI at 12 and 24 months. Additionally, these regression models show that clinicians can expect continued improvement throughout childhood.

Pediatric cranial deformations: demographic associations.

OBJECTIVE: No study has established a relationship between cranial deformations and demographic factors. While the connection between the Back to Sleep campaign and cranial deformation has been outlined, considerations toward cultural or anthropological differences should also be investigated. METHODS: The authors conducted a retrospective review of 1499 patients (age range 2 months to less than 19 years) who presented for possible trauma in 2018 and had a negative CT scan. The cranial vault asymmetry index (CVAI) and cranial index (CI) were used to evaluate potential cranial deformations. The cohort was evaluated for differences between sex, race, and ethnicity among 1) all patients and 2) patients within the clinical treatment window (2-24 months of age). Patients categorized as "other" and those for whom data were missing were excluded from analysis. RESULTS: In the CVAI cohort with available data (n = 1499, although data were missing for each variable), 800 (56.7%) of 1411 patients were male, 1024 (79%) of 1304 patients were Caucasian, 253 (19.4%) of 1304 patients were African American, and 127 (10.3%) of 1236 patients were of Hispanic/Latin American descent. The mean CVAI values were significantly different between sex (p < 0.001) and race (p < 0.001). However, only race was associated with differences in positional posterior plagiocephaly (PPP) diagnosis (p < 0.001). There was no significant difference in CVAI measurements for ethnicity (p = 0.968). Of the 520 patients in the treatment window cohort, 307 (59%) were male. Of the 421 patients with data for race, 334 were Caucasian and 80 were African American; 47 of the 483 patients with ethnicity data were of Hispanic/Latin American descent. There were no differences between mean CVAI values for sex (p = 0.404) or ethnicity (p = 0.600). There were significant differences between the mean CVAI values for Caucasian and African American patients (p < 0.001) and rate of PPP diagnosis (p = 0.02). In the CI cohort with available data (n = 1429, although data were missing for each variable), 849 (56.8%) of 1494 patients were male, 1007 (67.4%) of 1283 were Caucasian, 248 (16.6%) of 1283 were African American, and 138 patients with ethnicity data (n = 1320) of Hispanic/Latin American descent. Within the clinical treatment window cohort with available data, 373 (59.2%) of 630 patients were male, 403 were Caucasian (81.9%), 84 were African American (17.1%), and 55 (10.5%) of 528 patients were of Hispanic/Latin American descent. The mean CI values were not significantly different between sexes (p = 0.450) in either cohort. However, there were significant differences between CI measurements for Caucasian and African American patients (p < 0.001) as well as patients of Hispanic/Latin American descent (p < 0.001) in both cohorts. CONCLUSIONS: The authors found no significant associations between cranial deformations and sex. However, significant differences exist between Caucasian and African American patients as well as patients with Hispanic/Latin American heritage. These findings suggest cultural or anthropological influences on defining skull deformations. Further investigation into the factors contributing to these differences should be undertaken.

Positional posterior plagiocephaly: a single-center review.

OBJECTIVE: The authors sought to assess the prevalence and severity of positional posterior plagiocephaly (PPP) in the pediatric population at a tertiary care center. METHODS: The authors conducted a retrospective review of 1429 consecutive patients aged 2 months to 18 years who presented with head trauma and a negative CT scan in 2018. The cohort was stratified by age. The cranial vault asymmetry index (CVAI) was calculated at the superior orbital rim. Asymmetry was categorized according to the following CVAI scores: mild (3.5%-7%), moderate (7%-12%), and severe (> 12%). Patients were grouped by age to assess PPP at different stages of head development: group 1, 2-5 months; group 2, 6-11 months; group 3, 12-23 months; group 4: 2-4 years; group 5, 5-8 years; group 6, 9-12 years; and group 7, 13-18 years. Patients with a history of shunted hydrocephalus, craniosynostosis, skull surgery, or radiographic evidence of intracranial trauma were excluded. RESULTS: The overall cohort prevalence of PPP was 24.8% (354 patients). PPP prevalence was higher among younger patients from groups 1-3 (40.4%, 33.5%, and 0.8%, respectively). There was a continued decline in PPP by age in groups 4-7 (26.4%, 20%, 20%, and 10.8%, respectively). Mild cranial vault asymmetry was noted most often (78.0%, 276 patients), followed by moderate (19.5%, 69 patients) and severe (2.5%, 9 patients). There were no patients in group 6 or 7 with severe PPP. CONCLUSIONS: PPP is prevalent in pediatric populations and most commonly presents as a case of mild asymmetry. Although there was an overall decline of PPP prevalence with increasing age, moderate asymmetry was seen in all age groups. No patients in the cohort had severe asymmetry that persisted into adolescence.