Remembering to remember: prospective memory in children with epilepsy.

Prospective memory, the ability to remember to perform an intended act in the future, is a complex process that involves several stages and cognitive domains. This study sought to investigate prospective memory functioning in children with idiopathic epilepsy using tasks from the Rivermead Behavioral Memory Test for Children (RBMT-C) and the Memory for Intentions Screening Test for Youth (MISTY). Performances on prospective memory task characteristics of the MISTY (i.e., cue-type, length of time delay, and response type) were also compared between and across participant groups. Healthy children (N = 26) were found to have higher overall IQ and verbal IQ scores when compared to children with epilepsy (N = 19). Group differences in prospective memory functioning were found in subtests of the RBMT-C but not on the MISTY. Lastly, while there was no significant interaction effect between the groups and MISTY task characteristics, main effects were found across participant groups; all participants performed better on event-based tasks when compared to time-based tasks and on two-minute when compared to 10-minute time delays. Overall, findings suggest potential differences in cognitive functioning, particularly in IQ and prospective memory, in children with idiopathic epilepsy, though due to differences in findings across prospective memory tasks, further research is warranted to more definitively ascertain the extent, if any, of prospective memory deficits in children with epilepsy.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Inherited Pain Syndromes and Ion Channels.

Individuals rely on the perception of pain to avoid injury, to signal disease, and to warn about tissue inflammation and damage. However, the inheritance of inappropriate, extreme, or inadequate pain production is a source of significant human suffering. Substantial progress has been made in our understanding of the genetics and pathophysiology of pain through the study of individuals and families with several specific inherited pain syndromes. These studies have led to the discovery of a number of gene mutations associated with specific ion channel disturbances that produce familial inherited pain sensitivity and insensitivity syndromes. The sodium channel has been identified as the primary determinant of most of these syndromes. This article focuses on the inherited pain syndromes and their corresponding ion channel mutations. There is hope that through continued research into these ion channels and pain syndromes, targeted drug therapy would be fruitful and beneficial to those afflicted.

Tuberous sclerosis complex.

Tuberous sclerosis complex is an autosomal-dominant, neurocutaneous, multisystem disorder characterized by cellular hyperplasia and tissue dysplasia. The genetic cause is mutations in the TSC1 gene, found on chromosome 9q34, and TSC2 gene, found on chromosome 16p13. The clinical phenotypes resulting from mutations in either of the 2 genes are variable in each individual. Herein, advances in the understanding of molecular mechanisms in tuberous sclerosis complex are reviewed, and current guidelines for diagnosis, treatment, follow-up, and management are summarized.

Similar trends in serum VEGF-D levels and kidney angiomyolipoma responses with longer duration sirolimus treatment in adults with tuberous sclerosis.

CONTEXT: We have previously shown that serum VEGF-D is elevated at baseline, correlates with kidney angiomyolipoma size at baseline and 12 months, and decreases with sirolimus treatment in adults with tuberous sclerosis complex (TSC). To further investigate the utility of serum VEGF-D for longer term monitoring of TSC kidney disease, we present VEGF-D level results with 24 month follow-up. OBJECTIVE: To compare 24 month VEGF-D levels in two subgroups of sirolimus treated patients (OFF SIROLIMUS AFTER 12 MONTHS or ON SIROLIMUS AFTER 12 MONTHS). DESIGN AND INTERVENTION(S): Serum VEGF-D was measured in samples collected from subjects enrolled in a phase 2 multicenter trial evaluating sirolimus for the treatment of kidney angiomyolipomas associated with TSC or TSC/LAM. All participants were treated with sirolimus from 0-12 months. During months 12-24, sirolimus was discontinued in one subgroup. The other subgroup was treated with additional sirolimus. SETTING: Adult TSC participants were recruited from six clinical sites in the United States (comprehensive TSC clinics, 5; urology clinic, 1). PATIENTS: There were 28 TSC patients who completed all 24 months of the study and serum samples were available at 24 months from 18/28 patients. MAIN OUTCOME MEASURE(S): We compared the percent change in VEGF-D levels (baseline to 24 months) in patients from the two treatment subgroups. RESULTS: At 24 months, VEGF-D levels decreased by 67% compared with baseline (to 787 ± 426 pg/ml) in the ON SIROLIMUS AFTER 12 MONTHS group versus a 13% decrease (to 2971 ± 4014 pg/ml) in the OFF SIROLIMUS AFTER 12 MONTHS group (p=0.013, Mann-Whitney test). A similar trend was observed in kidney angiomyolipoma size but not in pulmonary function tests. Conclusions Serum VEGF-D may be useful for monitoring response to treatment with sirolimus and kidney angiomyolipoma size in patients with TSC, but confirmation is needed. TRIAL REGISTRATION: Clinical trials.gov NCT00126672.

The ebb and flow model: a philosophy of organizational learning in the academic health center.

Academic health centers (AHCs) have traditionally been a vibrant locale for cutting-edge medical research, androgogic education and innovative clinical care for the most vexing diseases. While these pursuits have coexisted and flourished, the realities of the health-care business environment have demanded reformatting and emulation of a corporate organizational model. This evolution has impacted the core identities of the AHC and challenged individual medical-educators, clinician-scientists and basic science investigators to persist and succeed in this milieu. The AHC has a unique capacity to muster the innate learning drive of these individuals into an organizational mission as it balances the pressures exerted from both the internal and external environments. The AHC as an organization can be viewed as an experimental condition with modifiable variables to which its professionals can react, adapt to, and transform. Organizational learning and change implementation is in essence an experiment in human behavior modification. While all individuals are subject to change, merely assembling them in a single locale determines neither a predictable homogeneous outcome nor the success of their endeavor. This article highlights some of these propositions and offers a philosophical approach to advance the AHC as an organization through the creativity and innovation of its professional ranks.

Autonomic dysfunction in childhood Guillain-Barré syndrome.

This investigation correlated incidence and degree of autonomic dysfunction with the degree of motor impairment in children hospitalized with Guillain-Barré syndrome. Motor weakness varies, as does the effect on autonomic function including heart rate, vasomotor stability, sweating, continence, and blood pressure. After Institutional Review Board approval, hospitalized patients with Guillain-Barré syndrome <19 years were included for retrospective chart review. There were 26 patients (12 boys), with a mean age of 11.3 years (range, 6-17 years). The average hospital stay was 10.6 days. Twenty-four (92%) recovered by 2 to 6 months without functional disability. Bradycardia and sweating disturbances were not observed. Hypertension occurred in 18 of 26 (69%) and tachycardia in 20 of 26 (77%) patients. The proportion of children with hypertension and/or tachycardia increased, as did the motor disability grade (P < .043 and P < .018, respectively). Hypertension occurred 9 to 15 days from symptom onset and within 24 to 48 hours of maximum motor disability in 89%. Multiple autonomic disturbances compound the course of childhood Guillain-Barré syndrome.

Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease.

BACKGROUND: Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2. METHODS: We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. RESULTS: 36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline). CONCLUSIONS: Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC. TRIAL REGISTRATION: Clinicaltrials.gov NCT00126672.

The relationship between the neuromodulator adenosine and behavioral symptoms of autism.

The neuromodulator adenosine is an endogenous sleep promoter, neuroprotector and anticonvulsant, and people with autism often suffer from sleep disruption and/or seizures. We hypothesized that increasing adenosine can decrease behavioral symptoms of autism spectrum disorders, and, based on published research, specific physiological stimuli are expected to increase brain adenosine. To test the relationship between adenosine and autism, we developed a customized parent-based questionnaire to assess child participation in activities expected to influence adenosine and quantify behavioral changes following these experiences. Parents were naive to study hypotheses and all conditions were pre-assigned. Results demonstrate significantly better behavior associated with events pre-established as predicted to increase rather than decrease or have no influence on adenosine. Understanding the physiological relationship between adenosine and autism could open new therapeutic strategies--potentially preventing seizures, improving sleep, and reducing social and behavioral dysfunction.

Clinical categorization of childhood syncope.

Syncope is a self-limited loss of consciousness produced by cerebral hypoperfusion/hypoxia. The objective of this study was to categorize the etiology and determine the frequency of concurrent epilepsy and whether laboratory testing is diagnostically useful. This was an institutional review board-approved retrospective chart review. Data were analyzed using descriptive statistics. There were 141 subjects (90 girls [63.8%]; mean age, 12.01 years). Of the syncope referrals, 86 of 123 (69.9%) had simple syncope, 35 of 123 (28.4%) had syncopal convulsions, and 2 of 123 (1.6%) had epilepsy alone. An electroencephalogram was performed in 64.7% (91/141) of the subjects but was diagnostic in 1 of 91 (1.4%) for epilepsy. Magnetic resonance imaging and/or computed tomography scans, electrocardiograms/Holter monitoring/stress testing, and blood tests were primarily normal or nondiagnostic, with 6 of 238 (2.5%) total tests contributing to the diagnosis. Primary neurocardiogenic syncope was identified in 78% (111/141) of all subjects (82% boys, 75% girls). Thirty-eight percent had syncopal convulsions, and 2.8% (4/141) had concurrent epilepsy. A detailed medical history was the most useful diagnostic tool.

Parental report of behavioral and cognitive diagnoses in childhood-onset epilepsy: A case-sibling-controlled analysis.

Evidence from multiple sources has highlighted the increased burden of cognitive, behavioral, and psychiatric disorders in childhood-onset epilepsy. Some of this increased morbidity, however, is attributable to underlying structural and metabolic insults. We assessed whether cognitive/behavioral/psychiatric disorders are associated with epilepsy of unknown or presumed genetic cause in young people with epilepsy (cases) compared with sibling controls. Our analyses included 217 cases who were enrolled in the Connecticut Study of Epilepsy between 1993 and 1997 and 217 sibling controls. Information was collected from a parent interview conducted 8-9years after the case was diagnosed with epilepsy. Relative to controls, parents were more likely to report that their case children were slow learners (OR=4.6, P<0.001), had a language disorder (OR=5.8, P<0.001), and had engaged in self-injurious behaviors other than suicide attempts (OR=5.5, P=0.013). Future research should examine whether these conditions first present during childhood influence prognosis into adulthood.

A 16-year-old girl with bilateral visual loss and left hemiparesis following an immunization against human papilloma virus.

We report the course of a 16-year-old girl who presented with near complete visual loss associated with chiasmal neuritis and a biopsy proven tumefactive demyelinating lesion on magnetic resonance imaging (MRI) in association with a recent immunization against human papilloma virus.

Acute tumefactive demyelinating lesions in a pediatric patient with known diagnosis of multiple sclerosis: review of the literature and treatment proposal.

Tumefactive demyelinating lesions are a known but uncommon complication of multiple sclerosis, a disease rarely reported in children. This is the case of a 16-year-old African American patient with multiple sclerosis, who developed 2 tumefactive demyelinating lesions. Review of the literature and our own experience helped formulate an algorithm for therapeutic options during an acute attack.