The Stress Phenotyping Framework: A multidisciplinary biobehavioral approach for assessing and therapeutically targeting maladaptive stress physiology.

Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers of toxic stress physiology; no biological, behavioral, or cognitive treatments specifically focused on normalizing toxic stress processes; and no agreed-upon guidelines for treating stress in the clinic or evaluating the efficacy of interventions that seek to reduce toxic stress and improve human functioning. We address these critical issues by (a) systematically describing key systems and mechanisms that are dysregulated by stress; (b) summarizing indicators, biomarkers, and instruments for assessing stress response systems; and (c) highlighting therapeutic approaches that can be used to normalize stress-related biopsychosocial functioning. We also present a novel multidisciplinary Stress Phenotyping Framework that can bring stress researchers and clinicians one step closer to realizing the goal of using precision medicine-based approaches to prevent and treat stress-associated health problems.

Wired for Threat: Clinical Features of Nervous System Dysregulation in 80 Children.

Background: The negative effect of perceived stress on health has become a cultural epidemic. Despite many health implications, the clinical impact of stress on the nervous system is not well understood. This case series describes the symptom profiles of 80 children with nervous system dysregulation attributed to maladaptive neuroendocrine responses to stress.

Arterial Wall Imaging in Pediatric Stroke.

Background And Purpose: Arteriopathy is common in childhood arterial ischemic stroke (AIS) and predicts stroke recurrence. Currently available vascular imaging techniques mainly image the arterial lumen rather than the vessel wall and have a limited ability to differentiate among common arteriopathies. We aimed to investigate the value of a magnetic resonance imaging-based technique, namely noninvasive arterial wall imaging (AWI), for distinguishing among arteriopathy subtypes in a consecutive cohort of children presenting with AIS.

The Utility of Collaterals as a Biomarker in Pediatric Unilateral Intracranial Arteriopathy.

Background: Intracranial arteriopathies are frequent causes of pediatric stroke and important risk factors for stroke recurrence. Without tissue diagnosis, vascular imaging is relied upon to identify the underlying etiology and prognosis. We hypothesized that children with unilateral intracranial arteriopathy with lenticulostriate collaterals would demonstrate distinct vascular outcomes compared with children without collaterals.

Clinical Profile Associated with Adverse Childhood Experiences: The Advent of Nervous System Dysregulation.

Background: We report the prevalence of children with multiple medical symptoms in a pediatric neurology clinic, describe their symptom profiles, and explore their association with adverse childhood experiences (ACEs).

Methods: We retrospectively reviewed 100 consecutive patients from an outpatient pediatric neurology clinic. Patients were included if they were ≥5 years old and reported ≥4 symptoms that were unexplained for ≥3-months.

Moyamoya Disease in Children: Results From the International Pediatric Stroke Study.

This study aimed to describe children with moyamoya disease from an international multicenter stroke database, and explore risk factors for stroke recurrence. We reviewed data of children >28-days old with moyamoya disease enrolled in the International Pediatric Stroke Study from January 2003 to March 2013. A total of 174 children from 32 sites and 14 countries had moyamoya disease; median age 7.

Subacute Sclerosing Panencephalitis: The Foothold in Undervaccination.

Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles infection. We present a case of a fully vaccinated 3-year-old boy who was diagnosed with and treated for autoimmune encephalitis before arriving at a diagnosis of SSPE. We discuss the challenges of diagnosing SSPE in developed countries.

Quality of Life in Pediatric Moyamoya Disease.

Background: Moyamoya disease (MMD) is a progressive intracranial arteriopathy with high risk of stroke. Its impact on quality of life is unstudied. We surveyed children with moyamoya disease and compared their quality of life to chronically ill children and children with stroke to better understand the impact of this diagnosis.

Vascular Imaging Outcomes of Childhood Primary Angiitis of the Central Nervous System.

Background: Inflammation affecting cerebral blood vessels is a common cause of stroke in children. Arterial abnormalities on vascular imaging are an important risk factor for stroke recurrence. We aimed to describe the vascular imaging outcomes in children with primary angiitis of the central nervous system after 12 months and identify factors associated with vascular progression and stroke recurrence.

Focal Cerebral Arteriopathy: The Face With Many Names.

Objective: Focal cerebral arteriopathy is a term used to describe unilateral intracranial arteriopathy involving the distal internal carotid artery and proximal segments of the middle and anterior cerebral artery. We describe the disease course of 10 pediatric arterial ischemic stroke patients with focal cerebral arteriopathy from a single quaternary-care center.

Methods: We retrospectively reviewed pediatric stroke patients with focal cerebral arteriopathy without lenticulostriate collaterals treated at our institution between 2005 and 2014.

Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

Placental pathology in neonatal stroke.

Objective: Neonatal stroke is increasingly recognized, and risk factors have been identified. The placenta has been implicated as a potential contributor to neonatal stroke; however, pathology has not been previously described. This case series systematically evaluates prenatal, maternal, and neonatal risk factors and describes placental pathology in 12 cases of neonatal stroke.

Brain biopsy in children with primary small-vessel central nervous system vasculitis.

Objective: Primary angiitis of the central nervous system in childhood (cPACNS) is an immune-mediated inflammatory process directed toward blood vessels in the central nervous system. It has been associated with variable clinical and radiological presentations, and devastating consequences without treatment. Brain biopsy is required for definitive diagnosis.

Treatment of small vessel primary CNS vasculitis in children: an open-label cohort study.

Background: There is no treatment protocol or standardised documentation of neurological outcome for patients with small vessel childhood primary angiitis of the CNS, a rare inflammatory brain disease. We aimed to assess a treatment regimen and describe long-term neurological outcomes in a cohort of children with this disorder.

Methods: We did a single-centre open-label cohort study in children with small vessel childhood primary angiitis of the CNS who were less than 18 years old at diagnosis.

Central nervous system vasculitis in children.

Purpose Of Review: To review the current literature of primary and secondary central nervous system vasculitis in children, to evaluate the evolving classification and to suggest an approach to diagnosis.

Recent Findings: Central nervous system vasculitis in children is a newly recognized inflammatory brain disease, which may develop as a primary condition, or secondary to an underlying systemic disease. Primary angiitis of the central nervous system of childhood (cPACNS) is a reversible cause of severe neurological impairment, including acute ischemic stroke, intractable seizures and cognitive decline.

The Ages and Stages Questionnaires: feasibility of use as a screening tool for children in Canada.

Objective: To determine the accuracy and feasibility of a monitoring tool completed by parents for screening at-risk and community infants and children for developmental problems.

Methods: We assessed 43 children following open-heart surgery and 68 community children (aged 4-36 mo) at prescribed intervals using the Ages and Stages Questionnaires (ASQ). Subjects were followed 3 years later (at age 5-6 yr) via telephone interview with their parents concerning developmental delay identified by physicians.

A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease?

Objective: The purpose of this study was to review the experience with herpes simplex encephalitis at the Hospital for Sick Children over the past 12 years.

Methods: All patients who were admitted to our institution with acute encephalitis between January 1994 and December 2005 were enrolled prospectively in an encephalitis registry. Children from the registry with herpes simplex encephalitis were included in this study; we detailed the clinical presentations, laboratory findings, electroencephalographic findings, diagnostic imaging findings, treatments, and outcomes for all cases.