Ricki Robinson

Brain-Derived Neurotrophic Factor and Autoantibodies to Neural Antigens in Sera of Children with Autistic Spectrum Disorders, Landau-Kleffner Syndrome, and Epilepsy

BACKGROUND Brain derived neurotrophic factor (BDNF) elevation in newborn sera predicts intellectual/social developmental abnormalities. Other autoantibodies (AAs) to endothelial cells (ECs) and myelin basic protein (MBP) are also elevated in some children. We tested relationships between BDNF, BDNF AAs, and other AAs in children with these disorders. METHODS BDNF levels and IgG/IgM autoantibodies to BDNF, ECs, MBP, and histones were measured in children with autism, childhood disintegrative disorder (CDD), pervasive developmental delay-not otherwise specified (PDD-nos), acquired epilepsy, Landau-Kleffner syndrome (LKS); healthy children (HC), and children with non-neurological illnesses (NNI). RESULTS Mean BDNF levels were elevated in children with autism and CDD, (p < or = 0.0002) compared to HC or NNI. Mean IgG and IgM BDNF AAs were elevated in children with autism, CDD and epilepsy (p < or = 0.0005) compared to HC but not to NNI. Mean IgM AA EC titers detected by immunocytochemistry were higher in autism, PDD-NOS, epilepsy, and LKS (p < or = 0.005) compared to HC and NNI. While mean ELISA IgG EC AAs were higher in autism and PPD-NOS (p < 0.005) compared to HC but not NNI, ELISA IgM EC AAs were higher in children with autism, CDD, PDD-NOS, and epilepsy compared to both HC and NNI (p < 0.0005). Mean anti-MBP IgG and IgM titers were higher in all study groups (p < 0.005) except for LKS compared to both HC and NNI. CONCLUSION Children with developmental disorders and epilepsy have higher AAs to several neural antigens compared to controls. The presence of both BDNF AAs and elevated BDNF levels in some children with autism and CDD suggests a previously unrecognized interaction between the immune system and BDNF.

Rhabdomyolysis with severe hypernatremia

Three children with severe hypernatremia presented with profound generalized weakness and biochemical evidence of rhabdomyolysis and myoglobinuria. These findings in combination have not been previously reported, to our knowledge, in children with severe hypernatremia. Unusual complications included respiratory failure in one child and cardiac arrhythmias in two children. All three children had acute renal insufficiency; one required peritoneal dialysis.

Guidelines for early identification, screening, and clinical management of children with autism spectrum disorders.

Congratulations to the American Academy of Pediatrics (AAP). Two of their recent clinical reports published in Pediatrics , “Identification and Evaluation of Children With Autism Spectrum Disorders”1 and “Management of Children With Autism Spectrum Disorders,”2 will enable pediatricians to address parent concerns sooner, facilitating the early identification of children with autism spectrum disorders (ASDs). As physicians and developmentalists with decades of accumulated experience in working with children with developmental challenges, we applaud and welcome these publications. However, we would like to expand on these reports. In this commentary we (1) describe a broader functional/developmental framework for screening for ASDs, (2) provide a critique of the current trend toward behavioral treatments as primary intervention strategies, and (3) present research evidence for functional/developmental approaches. A broader and more refined “functional” developmental framework3 looks for compromises in the childs healthy milestones and helps parents and other caregivers work with the child to improve that area of functioning and overall healthy progression.* This approach helps families identify challenges early in the first and second years of life and to begin to help their children before the 18- and 24-month screenings recommended by the AAP.4 An overfocus on specific problem behaviors without a framework for promoting healthy development may prove to be counterproductive.5 Screening that focuses on specific behaviors or symptoms (eg, whether a child responds to his or her name toward the end of the first year) may identify a percentage … Address correspondence to Stanley I. Greenspan, MD, 7201 Glenbrook Road, Bethesda, MD 20814. E-mail: stanleygreenspan{at}gmail.com

Impact of Recent Findings on Study Design of Future Autism Clinical Trials

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.

Childhood pheochromocytoma: treatment with alpha methyl tyrosine for resistant hypertension.

A 12-year-old boy with a norepinephrine-secreting pheochromocytoma that caused hypertension resistant to oral alpha adrenergic blockade is reported. Resistance to alpha adrenergic blocking agents developed when the patients daily propranolol dosage was lowered from 10 to 1 mg/kg. Subsequently, alpha methyl tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, controlled the patients blood pressure and was associated with reduction in total urinary catecholamine excretion. Norepinephrine content of the tumor and uninvolved adrenal gland removal at surgery was reduced. These findings confirm that alpha methyl tyrosine inhibited in vivo synthesis of catecholamines.

Reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine

The reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine were evaluated after administration to 16 4-6-year-old children. The vaccine contained toxoided lymphocytosis-promoting factor (6.0 micrograms/dose), filamentous haemagglutinin (70 micrograms/dose), agglutinogens (1.4 micrograms/dose) and the 69 kDa protein (approximately 8.0 micrograms/dose). The vaccine was extremely well tolerated with few minor side effects following immunization. Significant increases in antibodies to all pertussis vaccine components were noted. In summary, this double-strength acellular pertussis vaccine, containing a very high dose of filamentous haemagglutinin, had minimal reactogenicity and was immunogenic. These findings, as well as other studies with this vaccine, indicate that filamentous haemagglutinin is not a major determinant of vaccine reactogenicity.