Anesthetic Neurotoxicity in Children

The clinical pediatric anesthesiology community has been greatly affected by a growing body of research suggesting that sedative drugs and anesthetic agents may have long lasting detrimental neurocognitive effects in children. Various animal models have indicated apoptotic brain cell death and neurocognitive impairment following anesthetic exposure in early life. Although these studies cannot be directly extrapolated to anesthesia in children, parents and governmental regulatory agencies have been paying attention nonetheless. Adding to the evidence are a number of human epidemiologic studies that have documented neurologic deficits and cognitive decline following early anesthetic exposure. 1-4 Clinical studies in children exposed to general anesthesia have assessed outcome measures including academic performance or school readiness, validated neuropsychologic testing, and educational interventions for neurodevelopmental or behavioral problems.

HIV-associated neurocognitive disorders: recent advances in pathogenesis, biomarkers, and treatment

HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the “gold standard” of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND. However, questions remain regarding the utility of, optimal population for, and insensitivity of tests in mild HAND.Recognition of ongoing viral persistence and the inflammatory milieu in the central nervous system (CNS) has advanced our understanding of the pathogenesis of HAND and facilitated the development of biomarkers of CNS disease. The importance of the monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor neurotropism has been identified. Whilst biomarkers demonstrate monocyte activation, inflammation, and neuronal injury, they remain limited in their clinical utility. The improved understanding of pathogenic mechanisms has led to novel approaches to the treatment of HAND; however, despite these advances, the optimal management is still undefined.

Clinical Characteristics of Childhood-Onset (Juvenile) Huntington Disease: Report of 12 Patients and Review of the Literature

Whereas adult-onset Huntington disease is a well-characterized clinical entity, childhood-onset cases have not received as much attention. In this report, the clinical, demographic, and genetic characteristics in 12 patients with childhood-onset Huntington disease are presented and compared with data in the literature. The patients were divided into two groups based on age at onset of symptoms (< 10 or ≥ 10 years old). The majority of patients had onset of symptoms before 10 years of age and most at or below 5 years of age. The delay in diagnosis was longer in those with earlier onset of symptoms. Inheritance was paternal in all patients with onset beyond 10 years of age. We found a preponderance of male patients in the younger age at onset group and of female patients in the older age at onset group. The most frequent heralding symptom was cognitive decline in the group with earlier onset and oropharyngeal dysfunction in the later-onset group. Seizures occurred only in the younger age at onset group. Chorea was not a presenting sign but developed later in the course of the disease and, with dystonia, was more prevalent in the early age at onset group, whereas rigidity and bradykinesia were more prevalent in the older age at onset group. Patients in both groups developed gait, cognitive, and behavioral disorders at some point during the course of the disease. Furthermore, a slow and steady decline in IQ was observed on serial neuropsychologic testing in patients from both groups. Imaging studies were normal early and most commonly revealed neostriatal atrophy later in the course of the disease. In this report, we describe the characteristics of 12 patients with childhood-onset Huntington disease and review those previously reported, expanding our knowledge about the features of childhood-onset Huntington disease, underlining the differences with patients with adult-onset Huntington disease, and suggesting a differential phenotype within patients with childhood-onset Huntington disease depending on the age at onset. ( J Child Neurol 2006;21:223—229; DOI 10.2310/7010.2006.00055).

Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant

Research indicates that myeloablative hematopoietic cell transplantation (HCT) impairs neurocognitive function. However, prospective studies on long-term effects are lacking. This longitudinal study examined neurocognitive changes over the first year in 142 adult recipients of allogeneic HC transplants who received neuropsychologic testing before transplantation and again after 80 days and 1 year. Age-, sex-, and education-adjusted population-based standardized scores were used for normative comparisons. Performance on all tests declined from before transplantation to 80 days (P &lt; .05) and improved by 1 year (P &lt; .05), returning to pretransplantation levels on all tests except for grip strength and motor dexterity. Although verbal fluency and memory recovered by 1 year, both were below norms at all 3 testing times (P &lt; .01). Logistic regressions indicated that patients without chemotherapy, other than hydroxyurea, previous to HCT and patients not receiving chronic graft-versus-host disease (GVHD) medication at 1 year had lower risk of impaired function (P &lt; .05). In conclusion, HCT was associated with significant generalized decline in neurocognitive performance at 80 days, with subsequent recovery to pretransplantation levels by 1 year for most survivors, except on motor tasks. Results indicate that long-term cognitive decrements, as distinct from motor disabilities, infrequently derive directly from HCT. (Blood. 2004;104:3386-3392)

Outcomes of a Randomized Trial of Hyperfractionated Cranial Radiation Therapy for Treatment of High-Risk Acute Lymphoblastic Leukemia: Therapeutic Efficacy and Neurotoxicity

Purpose We evaluated 8-year survival and late neuropsychologic toxicity in children with acute lymphoblastic leukemia treated in a randomized clinical trial to test whether hyperfractionated (twice daily) cranial radiation therapy (CRT) can reduce incidence and severity of late toxicities associated with 18 Gy of CRT. Patients and Methods Between 1987 and 1995, 369 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for high-risk acute lymphoblastic leukemia were randomly assigned to conventionally fractionated CRT (CFX) or hyperfractionated CRT (HFX) to a total dose of 18 Gy. Neuropsychologic testing was completed for 125 of 287 children in continuous complete remission. Event-free and overall survival, as well as neuropsychologic function, were compared for the two arms of the protocol. Results Eight-year event-free survival (± SE) was 80% ± 3% for children randomly assigned to CFX and 72% ± 3% for HFX (P = .06). Overall survival was 85% ± 3% for CFX and 78% ± 3% for HFX (P = .06). CNS relapses occurred in 2.8% of patients receiving CFX and 2.7% receiving HFX (P = .99). Cognitive function for both groups was solidly in the average range, with no group differences in intelligence, academic achievement, visuospatial reasoning, or verbal learning. Children on the HFX arm exhibited a modest advantage for visual memory (P < .05). Conclusion HFX provides no benefit in terms of cognitive late effects and may compromise antileukemic efficacy. HFX should not be substituted for conventionally dosed CRT in children who require radiation therapy for treatment of acute lymphoblastic leukemia.