Cell type-specific gene expression dynamics during human brain maturation.

The human brain undergoes protracted post-natal maturation, guided by dynamic changes in gene expression. To date, studies exploring these processes have used bulk tissue analyses, which mask cell type-specific gene expression dynamics. Here, using single nucleus (sn)RNA-Sseq on temporal lobe tissue, including samples of African ancestry, we build a joint paediatric and adult atlas of 54 cell subtypes, which we verify with spatial transcriptomics. We explore the differences in cell states between paediatric and adult cell types, revealing the genes and pathways that change during brain maturation. Our results highlight excitatory neuron subtypes, including the LTK and FREM subtypes, that show elevated expression of genes associated with cognition and synaptic plasticity in paediatric tissue. The new resources we present here improve our understanding of the brain during a critical period of its development and contribute to global efforts to build an inclusive cell map of the brain.

Cerebrovascular Pressure Reactivity Has a Strong and Independent Association With Outcome in Children With Severe Traumatic Brain Injury.

OBJECTIVES: To examine cerebrovascular pressure reactivity index (PRx) in a large cohort of children with severe traumatic brain injury (sTBI) in association with physiologic variables and outcome. DESIGN: Retrospective observational cohort study. SETTING: Red Cross War Memorial Children's Hospital in Cape Town, South Africa. PATIENTS: Pediatric (≤ 14 yr old) sTBI patients with intracranial pressure (ICP) monitoring (postresuscitation Glasgow Coma Score [Glasgow Coma Scale (GCS)] of ≤ 8). MEASUREMENTS AND MAIN RESULTS: Data were analyzed from ICM+ files sampled at 100Hz. PRx (a mathematical indicator of pressure reactivity) was calculated as a moving correlation coefficient between ICP and mean arterial pressure (MAP) as previously described. Associations between PRx, age, GCS, ICP, MAP, and cerebral perfusion pressure (CPP) were examined with summary measures and correlation analysis using high-frequency data. Associations between PRx and mortality/outcome were examined with multivariable logistic regression analysis and the prognostic ability of PRx with receiver operating characteristic (ROCs) curves. The dataset included over 1.7 million minutes (28,634 hr) of MAP and ICP data in 196 children. The series mortality was 10.7% (21/196), and unfavorable outcome 29.6% (58/196). PRx had a moderate positive correlation with ICP ( r = 0.44; p < 0.001), a moderate negative correlation with CPP ( r = -0.43; p < 0.001), and a weak negative correlation with MAP ( r = -0.21; p = 0.004). PRx was consistently higher in patients with poor outcome and had a strong, independent association with mortality (ROC area under the curve = 0.91). A PRx threshold of 0.25 showed the best predictive ability for mortality. CONCLUSIONS: This is the largest cohort of children with PRx analysis of cerebrovascular reactivity to date. PRx had a strong association with outcome that was independent of ICP, CPP, GCS, and age. The data suggest that impaired autoregulation is an independent factor associated with poor outcome and may be useful in directing clinical care.

Balamuthia mandrillaris Granulomatous Amoebic Encephalitis: The First African Experience.

We report the first case of Balamuthia mandrillaris granulomatous amoebic encephalitis definitively acquired in Africa. Our case emphasizes initial nonspecific dermatological features, delays in confirmation of the diagnosis, difficulties accessing recommended medication, and uncertainty about optimal treatment of a disease with a frequently fatal outcome.

Hydrocephalus in Low and Middle-Income Countries - Progress and Challenges.

Hydrocephalus remains one of the most commonly treated neurosurgical conditions worldwide. Caring for patients with hydrocephalus requires infrastructure and political support and initiative; these are often difficult to obtain in low- and middle-income countries (LMICs). Some innovations that have arisen in LMICs have traveled up the financial gradient to high-income countries, such as the combination of endoscopic third ventriculostomy with choroid plexus coagulation to manage hydrocephalus. The development of neuro-endoscopy has played a major role in managing hydrocephalus worldwide; however, LMICs still face specific challenges, such as limited access to shunt hardware, a disproportionately high incidence of post-infectious hydrocephalus, unique microbiological spectra, and often poor access to follow-up care and neuroimaging. This has received increased attention since the Lancet Commission on Global Surgery. The goal of improving access to quality neurosurgical care through various initiatives in LMICs will be discussed in this manuscript. The need for neurosurgeons continues to grow in LMICs, where better access to neurosurgical care, adequate neurosurgical training and political support, and patient education are needed to improve the quality of life for patients with common neurosurgical conditions. Despite these challenges, treating hydrocephalus remains a worthwhile endeavor for many patients.

Management of Spasticity After Traumatic Brain Injury in Children.

Traumatic brain injury is a common cause of disability worldwide. In fact, trauma is the second most common cause of death and disability, still today. Traumatic brain injury affects nearly 475 000 children in the United States alone. Globally it is estimated that nearly 2 million people are affected by traumatic brain injuries every year. The mechanism of injury differs between countries in the developing world, where low velocity injuries and interpersonal violence dominates, and high-income countries where high velocity injuries are more common. Traumatic brain injury is not only associated with acute problems, but patients can suffer from longstanding consequences such as seizures, spasticity, cognitive and social issues, often long after the acute injury has resolved. Spasticity is common after traumatic brain injury in children and up to 38% of patients may develop spasticity in the first 12 months after cerebral injury from stroke or trauma. Management of spasticity in children after traumatic brain injury is often overlooked as there are more pressing issues to attend to in the early phase after injury. By the time the spasticity becomes a priority, often it is too late to make meaningful improvements without reverting to major corrective surgical techniques. There is also very little written on the topic of spasticity management after traumatic brain injury, especially in children. Most of the information we have is derived from stroke research. The focus of management strategies are largely medication use, physical therapy, and other physical rehabilitative strategies, with surgical management techniques used for long-term refractory cases only. With this manuscript, the authors aim to review our current understanding of the pathophysiology and management options, as well as prevention, of spasticity after traumatic brain injury in children.