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link to powerpoint presentation - Autism Forum Charlotte Pediatric ...

  1. 1. Autism Forum Charlotte Pediatric Society April 27, 2010 Moderator: Andrew W. Gunter, MD University Pediatrics, Medical Director
  2. 2. Panel Introduction • Dr. Christopher Magryta, MD Touchstone Health Associates, Integrative Pediatrician • Dr. Jean-Ronel Corbier, MD Pediatric Neurology Group Practice, Concord, NC • Dr. J. Edward Spence, MD Clinical Genetics Program, Carolinas Healthcare System • Dr. Sarah Spence, MD, PhD Pediatric Neurology, Pediatrics and Developmental Neuropsychiatry Branch, NIH
  3. 3. Case Presentation 3 and ½ year old ‘new patient’ problem visit Chief Complaint: Concerned with last pediatrician’s suspected diagnosis of autism in her son Birth Hx: G1nowP1 34 yo mother C-sec secondary to FTP Hyperemesis 1st trimester, Zofran,prn IDDM, insulin controlled BW: 8lb 2 oz, home at 72hrs on MBM PMedHx: Breast fed until 2 months Milk based formula started, colic
  4. 4. Case Presentation PMHx: Diagnosis of colic vs. milk protein allergy, Alimentum Age 1 Soy milk due to vomiting at attempt on whole milk DevHx: Gross motor rolled over at 6 mos. crawled at 8 mos. cruised at age 1 year walked at 17 mos. Social smiled spontaneously at 2 months
  5. 5. Case Presentation DevHx (cont.) Social ? Imaginative play Verbal babbled at 1 year, no real words currently 4 words and 2 word phrases, repeats a lot Fine Motor Scribbles with fist
  6. 6. Case Presentation Immunizations UTD Family Hx: ‘learning issues’ in maternal aunt’s daughter PE: Difficult, poor eye contact Hand flapping Ptosis R eyelid High arched palate Flat feet Mild distended abdomen
  7. 7. ‘Well?!?” the mom says anxiously.
  8. 8. Autism Spectrum Disorder Autism spectrum disorders are a collection of neurodevelopmental disorders which affect young children and adults and are characterized by impaired socialization, communication, and repetitive/stereotypical behaviors. Affect approximately 1:+/-120 children in the United States Males >Females Familial patterns, sibling learning issues High monozygotic twin concordance GI issues Seizures
  9. 9. DSM IV-TR Diagnostic Criteria for 299.00 Autistic Disorder A. A total of six (or more) items from (1), (2), and (3), with at least two from (1), and one each from (2) and (3) (1) qualitative impairment in social interaction, as manifested by at least two of the following: (a) marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction (b) failure to develop peer relationships appropriate to developmental level (c) a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest) (d) lack of social or emotional reciprocity (2) qualitative impairments in communication as manifested by at least one of the following: (a) delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime) (b) in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others (c) stereotyped and repetitive use of language or idiosyncratic language (d) lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level (3) restricted repetitive and stereotyped patterns of behavior, interests and activities, as manifested by at least two of the following: (a) encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus (b) apparently inflexible adherence to specific, nonfunctional routines or rituals (c) stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements) (d) persistent preoccupation with parts of objects B. Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play C. The disturbance is not better accounted for by Rett's Disorder or Childhood Disintegrative Disorder.
  10. 10. DSM IV Diagnostic Criteria for 299.00 Autistic Disorder A. A total of six (or more) items from (1), (2), and (3), with at least two from (1), and one each from (2) and (3) (1) qualitative impairment in social interaction, as manifested by at least two of the following: (a) marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction (b) failure to develop peer relationships appropriate to developmental level (c) a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest) (d) lack of social or emotional reciprocity (2) qualitative impairments in communication as manifested by at least one of the following: (a) delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime) (b) in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others (c) stereotyped and repetitive use of language or idiosyncratic language (d) lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level (3) restricted repetitive and stereotyped patterns of behavior, interests and activities, as manifested by at least two of the following: (a) encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus (b) apparently inflexible adherence to specific, nonfunctional routines or rituals (c) stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements) (d) persistent preoccupation with parts of objects B. Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play C. The disturbance is not better accounted for by Rett's Disorder or Childhood Disintegrative Disorder.
  11. 11. Linked Systems of Function and Dysfunction PDD Gut Brain Immune
  12. 12. C Magryta3/2009
  13. 13.  Remove  Elimination diet, antacids,  steroids  Replace  Enzymes, Betaine HCL  Reinoculate  Synbiotics  Repair  Supplements
  14. 14. Neurological Evaluation of Autism Jean-Ronel Corbier, MD Pediatric Neurologist Diplomate of the American Board of Psychiatry and Neurology
  15. 15. Autistic Symptoms  Self-stimulatory behaviors (‘stimming’ ‘self-stims,)  Sensory processing/integration dysfunction  Auditory defensiveness  Tactile defensiveness  Visual ‘stims’  Oral texture issues  Speech/language impediments:  Echolalia  Verbal apraxia  Zoning out spells  Self absorbed versus hyper focused versus seizures  Irritability, aggression, hyperactivity
  16. 16. 6 + Categories of Neurodiagnostic Evaluation  HISTORY (perinatal factors; primary vs regressive autism; development; paroxysmal changes)  PHYSICAL EXAMINATION (GENERAL AND NEUROLOGICAL)  General appearance (dysmorphic?)  Behavior (autistic behavior, e/o sensory processing difficulties, abnormal mvt…)  Head Circumference (microcephalic/macrocephalic?)  Skin (hypo/hyperpigmented lesions?- e.g.Tuberous sclerosis)  Motor (muscle tone, reflexes); Craniopathies, Cerebellar…  SENSORY SYSTEM  ELECTRODIAGNOSTIC  NEUROMETABOLIC/GENETIC  NEUROIMAGING (seizures, abnormal neuro exam)  NUTRITION (Cu, zn, ferritin, vitamin A/D, B vitamins, etc…)
  17. 17. NEUROIMAGING/NEURODIAGNOSTICS  CT  MRI  MRS  PET  SPECT  Routine EEG  Sleep-deprived EEG  Prolonged EEG  24 hour video EEG  Magnetoencephalography
  18. 18. Neurometabolic Disorders and Dysfunction in Autism Spectrum Disorders Nassim Zecavati, MD, MPH, and Sarah J. Spence, MD, PhD Current Neurology and Neuroscience Reports 2009, 9:129–136 Known metabolic disorders in autism  Mitochondrial disorder (HEADD-hypotonia, epilepsy, autism and developmental delay)  PKU  Creatine deficiency  Pediatric neurotransmitter disease  e.g. CNS Folate deficiency  Biotinidase deficiency  Succinic semialdehyde dehydrogenase (SSADH) deficiciency  Hypocholesterolemia  Including Smith-Lemli-Opitz syndrome  Methylation disorder
  19. 19. 4 Most Common Vegetables in our Children’s Diet  French Fries  French Fries  French Fries  Ketchup
  20. 20. NUTRITIONAL NEUROLOGY DEFICIENCY Dependency, Interdependency Responsiveness FOOD Allergy/SENSITIVITY Vitamin/mineral Vitamin/mineral Immune/food allergy Cofactors Vitamin/mineral Non-immune Pyridoxine-dependent epilepsy Folinic acid responsive Epilepsy B6-B12-Folate interdependency Pediatric Neurotransmitter Disease (PND) -CNS Folate deficiency Vitamin E deficiency Creatine deficiency Biotinidase deficiency Celiac disease -gluten ataxia Casein Gluten
  21. 21. Creatine and the Brain The synthesis of creatine Symptoms of brain creatine deficiency: -Developmental delay/regression -Mental retardation -Speech delay (usually severe) -Epilepsy -Autism
  22. 22. MRS is the Test of Choice for Detecting and Monitoring Disorders of Creatine Metabolism Pediatric Neurology - Volume 40, Issue 5 (May 2009) - Copyright © 2009 Elsevier
  23. 23. Role of Folate  Folate(s) [natural] verus Folic acid [synthetic]  Dietary forms (inactive) versus Cellular forms (active)  Role of B12 in synthesis of enzymatically active form  Role of Folate  Repair and maintenance of the human genome (via S- adenosylmethionine; MECP2)  Regulation of gene expression  Amino acid metabolism (Glycine, Glu, methionine, homocystine)  Myelin synthesis (via phospholipids biosynthesis)  Neurotransmitter synthesis (Serotonin, Catecholamines Melatonin) Source of Folate: green leafy vegetables [folate comes from Latin word “FOLIUM” (leaf) ]
  24. 24. Folate-Responsive Neurologic Diseases Pediatric Neurology - Volume 37, Issue 6 (December 2007) - Neurologic conditions associated with abnormal folate status 1. Decreased cerebrospinal fluid and normal serum folate levels: -Primary: Cerebral folate deficiency syndrome (1/3 have ASD) -Secondary: Associated with Rett, Aicardi-Goutieres, and Kearns-Sayre syndromes 2. Normal cerebrospinal fluid and serum folate levels -Folinic acid responsive seizures 3. Abnormal maternal and fetal folate status (congenital malformations): -Neural-tube defects -Genetic malformations (Down syndrome, Fragile X syndrome?) 4. Decreased cerebrospinal fluid and serum folate levels (systemic disorders) -Primary: Congenital folate malabsorption Inborn errors of folate metabolism -Secondary:Celiac disease, infiltrative disease, or surgical resection of the upper intestine, increased requirements, increased excretion, the use of antifolate drugs, altered hepatic function, inadequate dietary intake
  25. 25. EPILEPSY AND NUTRITION
  26. 26. B6, Autism and Epilepsy  B6-dependent seizures  Treatment: Pyridoxine 15 mg/kg/day  During illness/infection causing breakthrough seizures may double the dose temporarily  B6-dependent seizures and Autism/ASD  (J Child Neurol 2000;15: 763-765).  Pyridoxine-responsive seizures  Pyridoxal-dependent seizures  Pyridoxal 5 Phosphate (P5P) responsive seizures
  27. 27. B6 and Folate  Children with autism, seizures and metabolic disorders may not always be able to utilize B6 and Folate  Active form of pyridoxine (B6) is Pyridoxal 5- Phosphate or P5P  Active form of Folate in 5-MTHF which is responsive to Folinic Acid  In some conditions both P5P and Folinic acid are needed  Vitamins, Not Surgery: Spinal Fluid Testing in Hemispheric Epilepsy Pediatric Neurology - Volume 40, Issue 6 (June 2009)  Folinic Acid-Responsive Seizures Initially Responsive to Pyridoxine Pediatric Neurology - Volume 34, Issue 2 (February 2006)
  28. 28. Celiac Disease Crossroad between the gut, the immune system and the brain Neurologic conditions reported in Celiac Disease (in 10 % of cases)  Epilepsy (with and without cerebral calcification)- Pediatric Neurology 01-MAR- 2007; 36(3); 165-9  *Cerebellar ‘gluten’ ataxia- Neurology - 14-FEB-2006; 66(3): 373-7  Childhood stroke Pediatric Neurology- 01- AUG-2004 31(2):139-42  Gluten-sensitivity neuropathy- Neurology - 27-JUN-2006; 66(12): 1923-5  Opsoclonus-myoclonus- Pediatric Neurology 01-APR-2006; 34(4);312-4  Brainstem encephalitis- Neurology – APR-2007; 68 (16) Suppl 2
  29. 29. Occult celiac disease presenting as epilepsy and MRI changes that responded to gluten-free diet Neurology - Volume 68, Issue 7 (February 2007) - American Academy of Neurology A) T1 image showing contrast-enhancing gray and white matter lesions. B) T1 image 2 years later, showing new contrast-enhancing lesions. C) T1 image after 12 months on gluten-free diet, showing resolution of prior contrast-enhancing regions and no new lesions.
  30. 30. Headache and CNS white matter abnormalities associated with gluten sensitivity Neurology - Volume 56, Issue 3 (February 2001) MRI from four patients, showing range of white matter abnormalities encountered.
  31. 31. Treatment of low brain folate levels  Folinic acid (leucovorin)  Primary Cerebral Folate Deficiency • Initial dose: 0.5 -1 mg/kg/day • Maintenance dose: 0.5 – 2.5 mg/kg/dose  (may titrate monthly with additional 0.5 mg/kg/day) • V., Blau N.: Cerebral folate deficiency. Dev Med Child Neurol 46. 843- 851.2004  Secondary Cerebral Folate Deficiency (e.g. Rett) Ormazabal A., Artuch R., Vilaseca M.A., Aracil A., Pineda M.: Cerebrospinal fluid concentrations of folate biogenic amines and pterins in Rett syndrome: Treatment with folic acid. Neuropediatrics 6. 380-385.2005  Autism and develompmental delay Moretti P., Sahoo T., Hyland K., et al: Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology 64. 1088- 1090.2005
  32. 32. ZINC  Involved in cognition  Involved in neuropsychological development  Involved in speech development  Involved in sensory processing Frederickson CJ, SW, Frederickson CJ, et al. Importance of zinc in the central nervous system: the zinc containing neuron. J Nutr. 2000; 130:1471S-1483S
  33. 33. FERRITIN AND IRON DEFICIENCY IN AUTISM  Iron Deficiency in Autism and Asperger Syndrome Latif et al. Autism.2002; 6: 103- 114  Children with autism: effect of iron supplementation on sleep and ferritin. Dosman CF - Pediatr Neurol - 01-MAR-2007; 36(3): 152-8 Iron deficiency (with or without anemia) can affect  Sleep (restless sleep)  Behavior  Affect  Mood  Development
  34. 34. Children With Autism: Effect of Iron Supplementation on Sleep and Ferritin Pediatric Neurology - Volume 36, Issue 3 (March 2007)  43 children enrolled in this opened labeled pilot study  Most had restless sleep (77%)  Connection found between poor sleep and low Ferritin level  The majority improved significantly with Fe supplementation- 6 mg elemental Fe/kg/day over 8 weeks (mean increase from 15 microgram/L to 29mcg/L)
  35. 35. Vitamins, Not Surgery: Spinal Fluid Testing in Hemispheric Epilepsy Pediatric Neurology - Volume 40, Issue 6 (June 2009)  9 month old infant referred for brain surgery owing to refractory status epilepticus with a right hemispheric focus (MRI was normal)  Metabolic work up revealed abnormal CSF peak seen in folinic acid-responsive epilepsy  Infant treated with folinic acid (1mg/kg/day) and 5- pyridoxal phosphate or P5P (10 mg/kg/day)  Infant became seizure-free  No surgery performed  Weaned off of anticonvulsants (topiramate and phenobarbital)
  36. 36. Gastrointestinal Symptoms in Children with an Autism Spectrum Disorder and Language Regression Pediatric Neurology - Volume 39, Issue 6 (December 2008)  Cross-sectional study with 100 children  Structured interview using GI and familial autoimmune questionnaire  Children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%, P = 0.006) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%, P = 0.001) and of rheumatoid arthritis (30% vs 11%, P = 0.03).  An association was observed between children with language regression, a family history of autoimmune disease, and gastrointestinal symptoms. Additional studies are needed to examine a possible shared autoimmune process.
  37. 37. Encephalopathies/Enteropathies/ Immunopathies/Psychopathies
  38. 38. Application of Nutritional Neurology  All children may benefit from this approach  Specifically consider this approach in children with:  Poor dietary intake  Refractory neurological symptoms • Unresponsive to pharmacological interventions • Experiencing side effects from medications  Idiopathic conditions  Systemic disorders involving neurological, immunological and gastrointestinal
  39. 39. More on Autism …How Much of a Genetic Basis? J. Edward Spence, MD Charlotte Ped Society April 27, 2010
  40. 40. Autism and Genetics • Recognized familial basis of autism – Having one child with autism increases chance of another • Some syndrome associations • Some children with classic autism with no syndrome features • Communication problems common for many syndromes
  41. 41. Genetics of Autism • Recurrence risk (RR) if one affected: – 4% if affected a girl – 7% if affected a boy – If 2 children with autism, RR is 25-35% • 70% concordance in monozygotic twins – 3% concordance in dizygotic twins • 3-4X more males than females – ?X-linked genes have a role?
  42. 42. Genetic Eval of ASDs • Search for genetic basis in an individual • Majority with no genetic cause found – Some question rationale for testing • If cause found: – Parents can stop searching • Power in having a SPECIFIC diagnosis • Genetic counseling and RR estimation – Potential medical concerns can be evaluated – ?Targeted therapies: few at present
  43. 43. Genetic Eval of ASDs History: – Prenatal history; Family history; Medical history; Developmental history • Physical exam: – Syndromic features are usually a pattern of distinctive or abnormal features – Specific features that are abnormal (and normal) – Measurements of objective features • Wt/lgth/HC, hands, eyes, etc – Neurological features • Tone, reflexes, alertness – Behavioral features • Response to MD, allow exam or not, warm up/go slow
  44. 44. Genetic Analysis • Chromosome analysis – Look at all chromosomes under microscope • Chromosome microarray analysis – Array comparative genomic hybridization – Submicroscopic analysis of all duplications and deletions along length of chromosome • Single gene DNA analysis – Looks only for abnormalities in that gene
  45. 45. Genetic Eval of ASDs • Screening tests: – Chromosome analysis: 5-10% abnl – Chromosome microarray analysis: 10% more with abnormalities (deletion or duplication) • Most abnormalities found with this step – CNV’s: relevant vs benign? • Some are the first reported – Many that are clinically relevant are new mutation abnormalities • Some are familial
  46. 46. Genetic Eval of ASDs • Fragile X syndrome: up to 2% boys POS – X-linked single gene disorder – Boys affected with MR, behavioral problems, few physical abnormalities (long face, prom ears) – Up to 30% of girls with fragile X gene mutation have effects, some with MR – If diagnosed, then mother is carrier – Often no Fam Hx
  47. 47. Genetic Eval of ASDs • Fragile X syndrome
  48. 48. Genetic Eval of ASDs • Rett syndrome: up to 1% girls POSITIVE – X-linked gene, usually new mutation – Lethal in most male fetuses, few have been found positive (microcephaly, abnl neuro) – Girls with initial nl dev with plateau, regression, loss of speech and eye contact, microcephaly by age 2 • Now known to be much more variable – Specific gene test, depends on exam features
  49. 49. Genetic Eval of ASDs • Angelman syndrome: much less common • Chr 15 deletion in 80%; specific gene abnormality in most of rest (UBE3A) • No speech; developmental delays, seizures, unsteady movements – Microcephaly, broad mouth, frequent smiling are features that develop over time • UBE3A considered candidate for non- syndromic cause of ASD
  50. 50. Genetic Eval of ASDs • Angelman syndrome
  51. 51. Genetic Eval of ASDs • Other tests are considered depending on evaluation and physical features – Biochemical analyses • Smith-Lemli-Opitz s.: Cholest metab defect – Radiological evaluations • MRI – Any of numerous gene/DNA tests for specific syndromes depending on features • Tuberous sclerosis • Associations?: CACNA1C, CNTNAP2, SHANK3
  52. 52. Genetic Eval of ASDs • Many syndromes: with genetic testing available, phenotype has expanded to include many who would not be diagnosed previously • A wide screening process is performed to come to a specific diagnosis • Likelihood of finding dx as much as 20% – Often no dx in non-dysmorphic child
  53. 53. • So why are so few given a diagnosis? • Is there A gene for autism? • If we find the gene can we treat it? • No simple answers – Not just AD/AR/XL inheritance in most cases – Some other genetic interaction • Maybe a neurobiology dysfunction Genetic Eval of ASDs
  54. 54. Autism and Genetics • Multiple genes involved – Genetic heterogeneity • Research difficult if multiple genetic bases • Compare apples and oranges • Multiple associations of different gene locations with autism in individual families • Possible explanation – Gene regulation in brain • How genes turned off and on – Synaptic communication dysfunction
  55. 55. Autism and Genetics • Genetic research is like a puzzle – The more pieces you fit in the easier it is to finish the puzzle – Many are working on this • Among 30,000 genes that make at least 90,000 proteins, that is hard enough • If we have to analyze interactions of genes or proteins with other compounds, that makes it that much harder
  56. 56. THE AUTISMS … AND THE SEARCH FOR MEANINGFUL SUBTYPES Sarah Spence MD PhD Pediatrics and Developmental Neuropsychiatry Branch National Institute of Mental Health
  57. 57. Core Symptom Domains Social Impairment Repetitive Behaviors & Restricted Interests Speech/ Communication Deficits AUTISM Asperger’s AdaptedfromE. Hollander
  58. 58. Core Symptom Domains PLUS Associated Cognitive Features Social Impairment Repetitive Behaviors & Restricted Interests Speech/ Communication Deficits Asperger’s syndrome AUTISM Expressive/Receptive Language Disorders Mental Retardation AdaptedfromE. Hollander
  59. 59. Core Symptom Domains PLUS Associated Psychiatric Symptoms Social Impairment Repetitive Behaviors & Restricted Interests Speech/ Communication Deficits Asperger’s syndrome AUTISM Expressive/Receptive Language Disorders Mental Retardation ADHD Social Phobia OCD Aggression AdaptedfromE. Hollander
  60. 60. Core Symptom Domains PLUS Associated Medical Features Social Impairment Repetitive Behaviors & Restricted Interests Speech/ Communication Deficits Asperger’s syndrome AUTISM Expressive/Receptive Language Disorders Mental Retardation ADHD Social Phobia OCD Aggression Epilepsy- EEG abnormalitiesImmune Dysfunction Macrocephaly- Big Heads Motor problems: Apraxia GI disturbance AdaptedfromE. Hollander
  61. 61. Visualization of the PHENOME CLINICAL OR PHENOTYPIC VARIABILITY ??? Final common pathways leading to autistic outcomes ETIOLOGICAL VARIABILITY CONCEPT IS: There are many ways to trigger disruption of development AND there are many different outcomes of that disruption … but there is a bottleneck in the middle that has to be tied to biological systems that generate autistic behaviors … the proverbial black box Brain mechanisms
  62. 62. Phenotyping in Autism Spectrum Disorders: The NIMH – IRP model  Comprehensive history, medical and neurological examination  Systematic longitudinal observations to determine clinical course and developmental trajectories  Evaluate family history and environmental exposures (including prenatal exposures)  Utilize neuropsychological testing, neuroimaging and other modalities to localize pathology  Examine medical AND genetic models  Generate & test hypotheses of etiology and pathophysiology
  63. 63. So how do you look for subtypes?  Look at the behavioral factors that separate kids with ASD.  Regression vs early onset  Use the data from extensive medical investigation.  Imaging, EEG, PSG, immunological profiles, metabolic abnormalities, genetic differences, nutritional status, etc etc etc …
  64. 64. Another subtype: Remission  Autism is lifelong disorder but some children have optimal responses to intervention:  No longer autistic & functioning in academic settings without support  New study designed to identify  Characteristics associated with optimal treatment response in autism  Clinically meaningful autism subtypes  New avenues for treatment intervention
  65. 65. Currently Recruiting for Remitted Autism Protocol PI David Black  SUBJECTS  Children 8-17 years old  Children with autism  Children with confirmed history of autism but not currently autistic  Typically developing children  ASSESSMENT  Diagnostic Evaluation (inc Detailed Treatment Hx)  Neuropsychological Evaluation  Neuro Exam with Overnight EEG/Sleep Study  Structural MRI with DTI  Resting State fMRI
  66. 66. For more information…  Autism information from NIH  http://www.nimh.nih.gov/healthinformation/autismmenu.cfm  NIH Funding  Websites for NIMH, NICHD, NINDS, NIEHS, and NIDCD  Ongoing NIH-sponsored trials  http://clinicaltrials.gov  NIMH intramural program:  http://intramural.nimh.nih.gov/pdn/  (301) 435-7962
  67. 67. RILUZOLE for Repetitive Behaviors & Fixated Interests  Investigation into modulation of the circuitry posited to be involved in the generation of obsessive-compulsive symptomatology.  Modulation of glutamate, the main excitatory neurotransmitter in the circuit, may be beneficial.
  68. 68. RILUZOLE Study  PLACEBO-CONTROLLED TRIAL  60 SUBJECTS  30 with only OCD  30 with OCD plus an autism spectrum disorder, including PDD- NOS  12 weeks controlled trial (50:50 randomization), followed by 3 months of open-label riluzole (for all participants).  Measures include:  Repetitive behaviors and obsessions  Anxiety and depression  Side effects include:  Generally very well-tolerated with few side-effects  Some children developed liver enzymes elevations  Rare reports of more serious complications
  69. 69. Contact the UNC Research Registry for Information Toll-free 1-866-744-7879 http://cidd.unc.edu/registry Email Renee_Clark@unc.edu Imaging of Infants at High Risk for Autism (Baby Sibs Study) Language Pragmatic Skills in Children with Autism and Fragile X Syndrome MRI Study of Brain Development in School Aged Children with Autism Family Genetic Study of Language and Cognition in Autism and Fragile X Functional MRI Evaluation of the Effect of Medication in ASD Imaging Social and Cognitive Functioning in Autism Predicting Useful Speech in Children with Autism Study to Explore Early Development: Risk Factors for Autism and Developmental Delay Improving Metabolic Parameters of Antipsychotic Child Treatment Tactile Information Processing Study Psychophysiology of Affective Responses in Autism Early Intervention for Children Screened Positive by the First Year Inventory Sensory Experiences Project, Phase II Autism Research Studies at the University of North Carolina at Chapel Hill

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