Purpose of ReviewThis review provides guidance for acute spinal cord injury (SCI) management through an analytical assessment of the most recent evidence on therapies available for treating SCI, including newer therapies under investigation. We present an approach to the SCI patient starting at presentation to acute rehabilitation and prognostication, with additional emphasis on the pediatric population when evidence is available.Recent FindingsFurther studies since the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) demonstrated a potential functional outcome benefit with ultra-early surgical intervention ≤ 8 h post-SCI. Subsequent analysis of the National Acute Spinal Cord Injury Study (NASCIS) II and NASCIS III trials have demonstrated potentially serious complications from intravenous methylprednisolone with limited benefit. Newer therapies actively being studied have demonstrated limited or no benefit in preclinical and clinical trials with insufficient evidence to support use in acute SCI treatment.SummaryCare for SCI patients requires a multi-disciplinary team. Immediate evaluation and management are focused on preventing additional injury and restoring perfusion to the affected cord. Rapid assessment and intervention involve focused neurological examination, targeted imaging, and surgical intervention when indicated. There are currently no evidence-based recommendations for pathomechanistically targeted therapies.

Purpose of ReviewThis is an update of headache attributed to systemic disease and current therapeutic strategies. Clinical scenarios are discussed.Recent FindingsThe diagnosis of headache attributed to metabolic or systemic disorder appears in the Appendix of International Classification of Headache Disorders, Third Edition, and requires further evaluation and validation. However, recent studies characterizing headache appear in the literature. Specific treatment includes addressing underlying systemic disorders, managing concurrent primary headache, and treating comorbidities that may exacerbate headache. Evidence for specific treatment trials for headache as a symptom is lacking, including headaches post-COVID19 infection. Calcitonin gene-related peptide receptor antagonists and 5-HT1F receptor agonists are attractive options for migraine with vascular comorbidities, but long-term studies are needed. SummaryHeadache is commonly encountered as a manifestation or complication of systemic disease. Further research is needed to validate headache associated with systemic disorders and to determine optimal treatment strategies.

Purpose of ReviewTo summarize pathophysiology, key conflicts, and therapeutic approaches in managing concomitant severe acute brain injury (SABI) and acute respiratory distress syndrome (ARDS).Recent FindingsARDS is common in SABI and independently associated with worse outcomes in all SABI subtypes. Most landmark ARDS trials excluded patients with SABI, and evidence to guide decisions is limited in this population. Potential areas of conflict in the management of patients with both SABI and ARDS are (1) risk of intracranial pressure (ICP) elevation with high levels of positive end-expiratory pressure (PEEP), permissive hypercapnia due to lung protective ventilation (LPV), or prone ventilation; (2) balancing a conservative fluid management strategy with ensuring adequate cerebral perfusion, particularly in patients with symptomatic vasospasm or impaired cerebrovascular blood flow; and (3) uncertainty about the benefit and harm of corticosteroids in this population, with a mortality benefit in ARDS, increased mortality shown in TBI, and conflicting data in other SABI subtypes. Also, the widely adapted partial pressure of oxygen (PaO2) target of > 55 mmHg for ARDS may exacerbate secondary brain injury, and recent guidelines recommend higher goals of 80–120 mmHg in SABI. Distinct pathophysiology and trajectories among different SABI subtypes need to be considered.SummaryThe management of SABI with ARDS is highly complex, and conventional ARDS management strategies may result in increased ICP and decreased cerebral perfusion. A crucial aspect of concurrent management is to recognize the risk of secondary brain injury in the individual patient, monitor with vigilance, and adjust management during critical time windows. The care of these patients requires meticulous attention to oxygenation and ventilation, hemodynamics, temperature management, and the neurological exam. LPV and prone ventilation should be utilized, and supplemented with invasive ICP monitoring if there is concern for cerebral edema and increased ICP. PEEP titration should be deliberate, involving measures of hemodynamic, pulmonary, and brain physiology. Serial volume status assessments should be performed in SABI and ARDS, and fluid management should be individualized based on measures of brain perfusion, the neurological exam, and cardiopulmonary status. More research is needed to define risks and benefits in corticosteroids in this population.

Purpose of ReviewThis article introduces fundamental concepts in circadian biology and the neuroscience of sleep, reviews recent studies characterizing circadian rhythm and sleep disruption among critically ill patients and potentially links to functional outcomes, and draws upon existing literature to propose therapeutic strategies to mitigate those harms. Particular attention is given to patients with critical neurologic conditions and the unique environment of the neuro-intensive care unit.Recent FindingsCircadian rhythm disruption is widespread among critically ill patients and sleep time is reduced and abnormally fragmented. There is a strong association between the degree of arousal suppression observed at the bedside and the extent of circadian disruption at the system (e.g., melatonin concentration rhythms) and cellular levels (e.g., core clock gene transcription rhythms). There is a paucity of electrographically normal sleep, and rest-activity rhythms are severely disturbed. Common care interventions such as neurochecks introduce unique disruptions in neurologic patients. There are no pharmacologic interventions proven to normalize circadian rhythms or restore physiologically normal sleep. Instead, interventions are focused on reducing pharmacologic and environmental factors that perpetuate disruption.SummaryThe intensive care environment introduces numerous potent disruptors to sleep and circadian rhythms. Direct neurologic injury and neuro-monitoring practices likely compound those factors to further derange circadian and sleep functions. In the absence of direct interventions to induce normalized rhythms and sleep, current therapy depends upon normalizing external stimuli.

Purpose of the reviewMyotonic dystrophy types 1 and 2 are frequent forms of muscular dystrophies in adulthood. Their clinical differences need to be taken into account for the most appropriate treatment of patients. The aim of this article is to provide an overview on the current and upcoming therapeutic options for patients with myotonic dystrophy type 2 (DM2).Recent findingsAt the moment, no disease-modifying therapies are available for DM2; next-generation therapies may however be available in the near future. In the meanwhile, the symptomatic management of patients has greatly improved, thank to the production of consensus-based standards of care and the growing evidence of efficacy of anti-myotonic drugs, promising employment of cannabinoids for symptom’s relief, regular monitoring, and early detection of treatable extra-muscular manifestations.SummaryThe treatment of DM2 is currently symptomatic and relies on the coordinated intervention of a multidisciplinary team. It remains to be determined whether upcoming causal therapies for myotonic dystrophy type 1 will be applicable also in DM2.

Acute spontaneous subarachnoid haemorrhage (SAH) is a severe disease, frequently complicated by vasospasm and delayed cerebral ischaemia (DCI), which have a negative impact on prognosis. Imaging studies are essential in the diagnosis of SAH. In this article, we review the available imaging techniques for prediction, monitoring and diagnosis of these complications of SAH. Non-contrast computed tomography (CT) and transcranial Doppler (TCD) have been so far the mainly used techniques to evaluate SAH patients during the acute stage of disease and to screen for vasospasm and DCI. However, there have been new developments of brain imaging techniques, with the introduction of automated methods to quantify blood volume and cerebral flow velocities, and the use of perfusion studies that could contribute to predict or diagnose such complications. Magnetic resonance (MR) imaging studies are proving useful to evaluate early brain injury and to diagnose DCI. Newer angiography suites have sophisticated post-processing tools that quantify cerebral haemodynamics in SAH and may provide important clues for the diagnosis of vasospasm. Imaging studies are part of the standard management of patients with acute SAH. Blood quantification on CT and the evaluation of cerebral flow velocities on TCD are known to predict and monitor the occurrence of vasospasm. DCI has increasingly been recognized as the most clinically relevant complication of SAH but also the most difficult to predict. MR imaging is the most sensitive tool to diagnose DCI. Future developments in imaging are needed to predict this important complication and help to improve the prognosis of patients with SAH.

Purpose of ReviewOver the last years, our understanding of the molecular biology of pediatric brain tumors has vastly improved. This has led to more narrowly defined subgroups of these tumors and has created new potential targets for molecularly driven therapies. This review presents an overview of the latest advances and challenges of implementing targeted therapies into the clinical management of pediatric brain tumors, with a focus on gliomas, craniopharyngiomas, and medulloblastomas.Recent FindingsPediatric low-grade gliomas (pLGG) show generally a low mutational burden with the mitogen-activated protein kinase (MAPK) signaling presenting a key driver for these tumors. Direct inhibition of this pathway through BRAF and/or MEK inhibitors has proven to be a clinically relevant strategy. More recently, MEK and IL-6 receptor inhibitors have started to be evaluated in the treatment for craniopharyngiomas. Aside these low-grade tumors, pediatric high-grade gliomas (pHGG) and medulloblastomas exhibit substantially greater molecular heterogeneity with various and sometimes unknown tumor driver alterations. The clinical benefit of different targeted therapy approaches to interfere with altered signaling pathways and restore epigenetic dysregulation is undergoing active clinical testing. For these multiple pathway-driven tumors, combination strategies will most likely be required to achieve clinical benefit.SummaryThe field of pediatric neuro-oncology made tremendous progress with regard to improved diagnosis setting the stage for precision medicine approaches over the last decades. The potential of targeted therapies has been clearly demonstrated for a subset of pediatric brain tumors. However, despite clear response rates, questions of sufficient blood-brain barrier penetration, optimal dosing, treatment duration as well as mechanisms of resistance and how these can be overcome with potential combination strategies need to be addressed in future investigations. Along this line, it is critical for future trials to define appropriate endpoints to assess therapy responses as well as short and long-term toxicities in the growing and developing child.