Paediatric cerebral sinus vein thrombosis. A multi-center, case-controlled study

The etiology and pathophysiology of cerebral sinus venous thrombosis (CSVT) in the paediatric population is still poorly understood, and the role of thrombophilic risk factors remains to be elucidated. In our multi-center case-controlled study we studied 46 patients with CSVT diagnosed from April 1996 to December 2003, consecutively referred for thrombophilia work-up. The results of thrombophilia screen were compared to 112 healthy paediatric controls. Anticoagulant therapy was applied according to treating physicians' decisions, and all cases were prospectively followed for a median of 4.1 years. Of 46 children, 8 had CSVT diagnosed in the neonatal period and therefore were analyzed separately. The prevalence of single thrombophilia markers and combinations of thrombophilic risk factors were similar among cases and controls. Among children with CSVT co-morbid systemic illness was present in most patients at diagnosis. Seven out of 8 children with idiopathic CSVT had thrombophilic risk factors as compared to 31/38 patients with co-morbid conditions. Anticoagulation was initiated in most patients, 11/46 patients continued therapy for a total of one year or more post event. Neither clinical presentation nor initial treatment decisions were affected by presence of thrombophilic risk factors in our study group. Thrombophilia prevalence was not increased in children with CSVT as compared to controls, however thrombophilia was more frequent among children with idiopathic CSVT. Thus, those selected patients would benefit most from thrombophilia work-up, required for long-term therapy considerations.     

Cerebral sinovenous thrombosis in children

Cerebral sinovenous thrombosis (CSVT) is a rare but increasingly recognized disease process in children. In the pediatric population, the etiologies of CSVT are multiple and the outcomes are variable. The current therapies for CSVT include anticoagulation, thrombolysis, hydration, surgery, and supportive care. Adult studies, pediatric case studies, and expert opinion form the basis for these treatment strategies. International cooperative efforts are currently being undertaken to collect data on pediatric stroke patients, including CSVT. These multicenter collaborations are needed to increase our understanding of the incidence, risk factors, treatment modalities, and outcomes of CSVT in pediatric populations.     

The selective serotonin reuptake inhibitors controversy in the treatment of depression in children

Antidepressants are widely prescribed for children and adolescents, although data regarding their safety and efficacy are limited. The objective of this article is to review the origins of the controversy regarding the current use of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents. Two chief concerns drive the controversy: 1) the discovery of an increased risk of suicidal behaviors in those treated with SSRIs and 2) the efficacy of SSRIs in childhood and adolescent major depression is unclear. Various factors may account for the reported differences in outcomes for SSRI treatment in children and adolescents compared to adults. The past decade has shown a significant drop in the rate of adolescent suicide, which coincides with the onset of the use of these medications. Therefore, a reduction in the use of SSRIs in children and adolescents should be considered carefully.     

Tick-borne diseases

Tick-transmitted infectious agents have assumed increased importance as causes of human disease in the United States. During the past two decades, Lyme borreliosis, ehrlichiosis, and babesiosis have emerged as newly described tick-borne infectious diseases of significance for pediatricians and pediatric neurologists. In fact, the highest rates of infection for Lyme disease and Rocky Mountain spotted fever (RMSF), by decade of age, are in childhood. As such, tick-borne infectious disease are of considerable public health concern, particularly for children residing in endemic regions. RMSF and human ehrlichioses can be life-threatening but are also eminently treatable when recognized early. Delays in diagnosis and treatment can lead to adverse outcomes. This article reviews the clinical and epidemiological features of Lyme borreliosis, RMSF, and ehrlichiosis, important causes of neurological illness among children, and summarizes current therapeutic and preventive strategies.     

Neurologic, neuropsychologic, and electroencephalographic findings after European tick-borne encephalitis in children

Tick-borne European early summer meningoencephalitis is believed to be a benign disease in childhood. The causative RNA virus is from the same family as the West Nile virus, and the respective clinical presentations have many similarities. We studied 19 German children who had suffered from tick-borne encephalitis virus meningitis or meningoencephalitis in an endemic area and compared them with 19 matched controls. Epidemiologic data were consistent with known features of tick-borne encephalitis infection in southern Germany. None of the children studied had severe neurologic or neuropsychologic sequelae. One child developed significant clinical depression shortly after the illness. Electroencephalograms (EEGs) from children with tick-borne encephalitis were significantly slower on follow-up than control EEGs. After tick-borne encephalitis, children had a higher likelihood of having an impairment of attention and psychomotor speed. Using the Touwen neurologic examination, after tick-borne encephalitis, children had lower scores than control children on 4 of the 10 subsystems. Owing to the small sample size, it was difficult to identify risk factors for and predictors of adverse outcomes.     

Cerebral sinus venous thrombosis in Swiss children

Aim To describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Switzerland. Method Data on clinical features, neuroimaging, risk factors, and treatment were collected for all children in Switzerland younger than 16 years of age who had CSVT between January 2000 and December 2008. A follow‐up examination and a cognitive assessment were performed (mean follow‐up period 26mo). Differences between neonates and children (patients older than 28d) were assessed and predictors of outcome were determined. Results Twenty‐one neonates (14 males, seven females; mean age 9d, SD 8d) and 44 children (30 males, 14 females; mean age 8y 7mo, SD 4y 5mo) were reported. The incidence of paediatric CSVT in Switzerland was 0.558 per 100 000 per year. In neonates, the deep venous system was more often involved and parenchymal injuries were more common. The strongest predictor of poor outcome was neonatal age (odds ratio 17.8, 95% confidence interval 0.847–372.353). Most children showed global cognitive abilities within the normal range, but impairments in single cognitive subdomains were frequent. Interpretation Paediatric CSVT is rare. Its outcome is poor in neonates. Most children have good neurological outcomes, but some patients have individual neuropsychological impairments.     

An adult with childhood medical trauma treated with psychoanalytic psychotherapy and EMDR: a case study

PROBLEM: Adverse childhood experiences have been found to be a strong predictor of emotional and physical problems in adulthood. However, the long-term sequelae for children who have suffered critical illness and exposure to invasive medical procedures are less well documented. METHODS: This is a case study of an adult client who sought treatment for depression and attention deficit disorder. The psychotherapy treatment is discussed and the use of eye movement desensitization and reprocessing (EMDR) is described targeting a memory of a medical trauma resulting from a tonsillectomy when the client was 8 years old. CONCLUSIONS: Significant healing outcomes were attained as a result of the therapy, i.e., decreased depression, less hypervigilance, and increased ability to concentrate, which resulted in the discontinuation of medication for depression and ADHD as well as significant improvement in overall functioning.     

Outcome in children with symptomatic congenital cytomegalovirus infection

To determine factors that are associated with adverse developmental outcome after congenital cytomegalovirus infection, we reviewed the clinical, laboratory, and radiographic findings in 18 children with symptomatic congenital cytomegalovirus infections. When children with adverse outcomes (intelligence or developmental quotients of 50 or less, n = 10) were compared with children with mild sequelae (intelligence or developmental quotients of 70 or higher, n = 8), we found no relationship between developmental outcome and neonatal clinical features (birth weight, jaundice, hepatomegaly, splenomegaly, or petechiae). With the possible exception of intracranial calcifications, no single clinical or radiographic feature was associated with a specific developmental outcome. However, children who had postnatal microcephaly, postnatal seizures, and an abnormal central nervous system imaging study were more likely to have severe developmental sequelae.     

The genetics of childhood psychiatric disorders: a decade of progress

OBJECTIVE: To review the literature over the past decade on the genetics of childhood neuropsychiatric disorders. METHOD: A computerized search was performed for articles published in the past decade, and selected papers were highlighted. RESULTS: The past decade of research has illuminated the complex genetics of early-onset mental disorders. Advances in statistical methodologies and laboratory-based gene-hunting techniques are laying the foundation for a deeper understanding of both the biological and environmental factors that contribute to mental illness. Researchers are on the verge of identifying and characterizing genetic vulnerabilities involved in common childhood psychiatric syndromes. CONCLUSIONS: Although the study of the genetics of childhood psychiatric disorders has advanced significantly over the past decade, considerable work remains. The identification of genes conferring vulnerability to psychiatric illnesses will have the potential to transform the field by providing insight into both biological and environmental determinants that contribute to serious developmental and psychiatric disorders in children and adolescents. These advances promise new understanding and new avenues for prevention and treatment. They will also present physicians and families with significant clinical and ethical challenges.     

Outcomes of childhood epilepsy at age 33 years: A population‐based birth‐cohort study

Purpose: There is uncertainty about health and socioeconomic outcomes of children with epilepsy, knowledge of adult outcomes, and factors associated with adverse outcomes are essential to guide prognosis, improve management, and determine appropriate allocation of resources. Methods: A subgroup of 101 children with epilepsy (onset ≤ age 16 years) were previously identified and reported from the 1958 National Child Development Study (NCDS), a national United Kingdom birth cohort study. In the current study we examine outcomes of this unique childhood epilepsy subgroup at age 33 compared to unaffected NCDS cohort members in mental and general health, education and employment, marriage, and parenthood. Multivariable regression analyses were used to investigate factors (including etiology, cognitive development, parental interest, and childhood anxiety/depression at age 11 years) associated with adverse outcomes. Key Findings: Sixty‐five (66%) were still participating at 33 years. Median follow‐up after epilepsy onset was 28 years (range 17–33 years). Thirty participants [46%, 95% confidence interval (CI) 35–58] had epilepsy onset <5 years, 32 (49%, 95% CI 37–61) had “symptomatic” epilepsy, and 33 (51%, 95% CI 39–63) had idiopathic epilepsy. Thirty‐one participants (48%) reported being seen by their doctor for epilepsy in the preceding year, 27 (42%) were registered disabled, 39 (60%) had a drivers license, and 42 (65%) thought their epilepsy made it harder to get/keep a paid job. People who had childhood epilepsy had an increased risk of death [standardized mortality rate (SMR) 3.1, 95% CI 1.1–6.1]. Childhood epilepsy was associated with poor general and mental health at 33 years on univariable analyses, but not after adjusting for childhood cognitive development/comorbidities and anxiety over acceptance by peers/adults at age 11. Childhood epilepsy was an independent risk factor for not being married [odds ratio (OR) 0.45, 95% CI 0.05–0.94] or being a parent (OR 0.67, 95% CI 0.42–0.91). People with childhood epilepsy and poor cognitive development compared to those with poor cognitive development without epilepsy had a greater proportion with subsequent poor mental health (56% vs. 24%, difference in proportion 33%, 95% CI 12–50), and a lesser proportion who married (39% vs. 78%, difference in proportion −39%, 95% CI −56 to −19). Significance: Compared to the unaffected population, children with epilepsy with good cognitive development/without comorbidities have similar adult health, educational, and employment outcomes but have difficulties with establishing and maintaining personal relationships. A combination of having childhood epilepsy plus poor cognitive development is more likely to be associated with adverse outcomes compared to having poor cognitive development without childhood epilepsy. Children with epilepsy have increased risk of death compared to the rest of the population. Pharmacologic management alone is inadequate and long‐term psychosocial support is needed.     

Factors influencing real-life use of direct oral anticoagulants in patients with cerebral sinus and venous thrombosis

BackgroundDirect oral anticoagulants (DOAC) are advocated as equally effective to vitamin K antagonists (VKA) for the treatment of patients with cerebral sinus and venous thrombosis (CSVT). However, data concerning the real-life management practices in CSVT patients are is lacking.MethodsProspective CSVT databases from four large academic medical centers were retrospectively studied. Demographics, clinical presentations, risk factors, radiological and outcome parameters were compared between CSVT patients treated with DOAC and VKA.ResultsOut of 504 CSVT patients, 43 (8.5%) were treated with DOAC, and the remaining 461 (91.5%) were treated with VKA. All patients with antiphospholipid syndrome (APLA) were treated with VKA (61 vs. 0, p=0.013). Patients with a history or presence of malignancy were also more often treated with VKA (16% vs. 5%, p=0.046). Other risk factors for thrombosis did not differ between the groups. There were no differences in clot extent or location and no differences in the percentage of favorable outcomes or mortality were observed.ConclusionOur data suggests that only malignancy and antiphospholipid antibodies significantly influenced physician's decisions towards choosing VKA rather than DOAC. DOAC appear to be as effective and safe as VKA in patients with CSVT.     

Childhood medulloblastoma: progress and future challenges

Medulloblastoma and other primitive neuroectodermal tumors are the most common malignant tumors of childhood. Progress has been slowly made in the management of such tumors. Long-term neurocognitive sequelae of treatment in children with medulloblastoma are common and recent treatment trials have attempted to reduce the amount of craniospinal radiation therapy or delay radiation therapy in attempts to reduce such sequelae. Surgery remains a critical component of treatment, although there is increasing concern about surgically-related complications, including the cerebellar mutism syndrome. For older children, craniospinal radiation remains an integral part of management. However, recent studies have suggested an excellent outcome after reduced-dose craniospinal radiation therapy and adjuvant chemotherapy. The role of chemotherapy is expanding for children with medulloblastoma and is now presently a component of protocols for children with average-risk and poor-risk disease. For children with poor-risk disease, intensifications of chemotherapy both during and after radiation therapy are presently being explored. Treatment of infants and young children with medulloblastoma remains problematic and a variety of different approaches are being investigated with the aims of both improving outcome and reducing long-term sequelae.     

Role of endogenous testosterone concentration in pediatric stroke

Previous studies have indicated a male predominance in pediatric stroke. To elucidate this gender disparity, total testosterone concentration was measured in children with arterial ischemic stroke (AIS; n = 72), children with cerebral sinovenous thrombosis (CSVT; n = 52), and 109 healthy controls. Testosterone levels above the 90th percentile for age and gender were documented in 10 children with AIS (13.9%) and 10 with CSVT (19.2%), totaling 16.7% of patients with cerebral thromboembolism overall, as compared with only 2 of 109 controls (1.8%; p = 0.002). In multivariate analysis with adjustment for total cholesterol level, hematocrit, and pubertal status, elevated testosterone was independently associated with increased disease risk (odds ratio [95% confidence interval]: overall = 3.98 [1.38–11.45]; AIS = 3.88 [1.13–13.35]; CSVT = 5.50 [1.65–18.32]). Further adjusted analyses revealed that, for each 1nmol/l increase in testosterone in boys, the odds of cerebral thromboembolism were increased 1.3‐fold. Ann Neurol 2009;66:754–758     

Life Span Studies of ADHD—Conceptual Challenges and Predictors of Persistence and Outcome

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span.     

Preventing neurocognitive late effects in childhood cancer survivors

Neurocognitive late effects are common sequelae of cancer in children, especially in those who have undergone treatment for brain tumors or in those receiving prophylactic cranial radiation therapy to treat leukemia. Neurocognitive morbidity in attention, executive functioning, processing speed, working memory, and memory frequently occurs and contributes to declines in intellectual and academic abilities. Oncologists are faced with the challenge of using the most effective, often the most intense, therapy to achieve the primary goal of medical success, balanced with the desire to prevent adverse late effects. Not all children with similar diagnoses and treatment have identical neurocognitive outcomes; some do very poorly and some do well. Attention now turns to the reliable prediction of risk for poor outcomes and then, using risk-adapted therapy, to preserve neurocognitive function. Prevention of late effects through rehabilitative strategies, continuation of school, and pharmacotherapy will be explored.     

Family impact of neurodevelopmental late effects in survivors of pediatric cancer: review of research, clinical evidence, and future directions

Children and adolescents who have survived childhood cancer are vulnerable to late effects of their disease and treatment experience, including both physical and psychological sequelae. The neurodevelopmental (ND) sequelae (e.g., difficulties with attention, memory, information processing, and other executive functions) faced by children surviving central nervous system (CNS) cancers or CNS treatments can have a range of effects on their psychological adjustment and quality of life as they reintegrate into school and social settings. Survivors facing such difficulties may be influenced by their family environment, and these struggles may in turn impact the perceived burden of their parents and family system, suggesting a bidirectional framework for understanding the impact of ND late effects within the family. The current study summarizes the following: Findings of family outcomes in children with ND late effects of cancer treatment; evaluation of methodological and measurement issues; the importance of examining bidirectional family-child influences; and implications for future survivorship research and clinical care addressing the role of ND late effects from a systems perspective.     

Treatment of childhood arterial ischemic stroke

Traditional risk factors associated with adult arterial ischemic stroke (AIS; ie, hypertension, hyperlipidemia, diabetes, smoking, and atherosclerosis) are relatively rare in children. Childhood AIS is instead associated with a variety of conditions including cerebral arteriopathies, congenital heart disease, infection, head and neck trauma, sickle cell anemia, and prothrombotic abnormalities. Although the pathophysiology and outcomes of adult AIS differ significantly from those in childhood AIS, therapeutic management remains similar, largely because of the paucity of evidence from devoted pediatric observational studies and clinical trials. The purpose of this article is to review the current guidelines and evidence in the treatment of childhood AIS, within the context of that which exists in adult AIS. Medical management of hypoxia, hyperglycemia, fever, blood pressure, and increased intracranial pressure has been insufficiently investigated in childhood stroke, resulting in a lack of guidance in these areas. Although acute antithrombotic management in childhood AIS has received relatively greater attention in published recommendations, it is based almost exclusively on consensus and expert opinion, and differs considerably among existing pediatric guidelines. Rehabilitation therapy in childhood AIS has great potential for meaningful improvements in long-term outcomes, especially given the plasticity of the young brain; however, little guidance for rehabilitative measures is provided by published recommendations. Ongoing and future multicenter cohort study efforts, and ultimately devoted pediatric clinical trials, will be essential to establish comprehensive evidence-based guidelines for the treatment of childhood AIS.     

Cognitive styles and psychological functioning in rural South African school students: Understanding influences for risk and resilience in the face of chronic adversity

Adverse childhood experiences can show lasting effects on physical and mental health. Major questions surround how children overcome adverse circumstances to prevent negative outcomes. A key factor determining resilience is likely to be cognitive interpretation (how children interpret the world around them). The cognitive interpretations of 1025 school children aged 10–12 years in a rural, socioeconomically disadvantaged area of South Africa were examined using the Cognitive Triad Inventory for Children (CTI-C). These were examined in relation to psychological functioning and perceptions of the school environment. Those with more positive cognitive interpretations had better psychological functioning on scales of depression, anxiety, somatization and sequelae of potentially traumatic events. Children with more negative cognitions viewed the school-environment more negatively. Children living in poverty in rural South Africa experience considerable adversity and those with negative cognitions are at risk for psychological problems. Targeting children's cognitive interpretations may be a possible area for intervention.     

Psychiatric aspects of pediatric cancer

Recent progress in the understanding of psychological and social factors related to cancer is important because cancer is the most common fatal disease of childhood and adolescence. Research interest in children and adolescents who have survived cancer also has increased over the past several years. Attention has focused on the long-term social outcomes of these children and adolescents. With increased survival, quality-of-life issues have assumed a more prominent role in the treatment protocols being developed for childhood cancer. The presence of long-lasting uncertainty about recurrence of the disease or second malignancy together with recognition of cognitive and physical side effects of treatment make childhood cancer a potentially chronic condition. Survivors experience actual or potential threats to future health; more than half have medical cognitive or psychological problems.     

Attention deficit hyperactivity disorder (ADHD) in childhood epilepsy

ADHD and epilepsy common are both common childhood disorders and both can have significant negative consequences on a child's behavioural, learning, and social development. Both conditions can co-occur and population studies suggest that the prevalence of ADHD in childhood epilepsy is between 12 and 17%. The prevalence of epilepsy in ADHD is lower but it is not clear if the rate of epilepsy is higher in ADHD populations than in the general population. There is a higher occurrence of ADHD - Primarily Inattentive subtype in children with epilepsy and the reasons for this are not altogether clear but attention difficulties are very prevalent in childhood epilepsy. Seizure/epilepsy variables do not appear to be important correlates in most cases of ADHD in epilepsy although they may play a role in some cases. Individuals with both epilepsy and intellectual disability may be at higher risk for significant ADHD symptoms although screening and assessment in children with intellectual disability and epilepsy may be challenging. Children with epilepsy and ADHD are likely to be at higher risk for more negative outcomes in school and in terms of quality of life compared with children with epilepsy alone. Published studies on the treatment of ADHD in childhood epilepsy have focussed exclusively on the use of psychopharmacology and particularly methylphenidate. Although methylphenidate appears to be effective for some children with epilepsy the issue of whether it may lower seizure threshold continues to be debated. Children with epilepsy are at significant risk for ADHD and there is a need for more studies focussing on safe and efficacious interventions for symptoms of ADHD in this population.