Autism Forum Charlotte Pediatric Society

April 27, 2010Moderator: Andrew W. Gunter, MD

University Pediatrics, Medical Director

Panel Introduction

• Dr. Christopher Magryta, MDTouchstone Health Associates, Integrative Pediatrician

• Dr. Jean-Ronel Corbier, MDPediatric Neurology Group Practice, Concord, NC

• Dr. J. Edward Spence, MDClinical Genetics Program, Carolinas Healthcare System

• Dr. Sarah Spence, MD, PhDPediatric Neurology, Pediatrics and DevelopmentalNeuropsychiatry Branch, NIH

Case Presentation

3 and ½ year old ‘new patient’ problem visitChief Complaint: Concerned with last pediatrician’s

suspected diagnosis of autism in her son

Birth Hx: G1nowP1 34 yo motherC-sec secondary to FTPHyperemesis 1st trimester,

Zofran,prn IDDM, insulin controlledBW: 8lb 2 oz, home at 72hrs on

MBMPMedHx:Breast fed until 2 months

Milk based formula started, colic

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 yearwalked at 17 mos.Social smiled spontaneously at 2 months

Case Presentation

DevHx (cont.) Social? Imaginative playVerbalbabbled at 1 year, no real wordscurrently 4 words and 2 word phrases, repeats a lotFine MotorScribbles with fist

Case Presentation

Immunizations UTDFamily Hx: ‘learning issues’ in maternal

aunt’s daughterPE: Difficult, poor eye contact

Hand flappingPtosis R eyelidHigh arched palateFlat feetMild distended abdomen

‘Well?!?” the mom says anxiously.

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 StatesMales >FemalesFamilial patterns, sibling learning issuesHigh monozygotic twin concordanceGI issuesSeizures

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.

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.

Linked Systems of Function and Dysfunction

PDD

Gut

BrainImmune

C Magryta3/2009

Four R ApproachRemove

Elimination diet, antacids, steroids

Replace Enzymes, Betaine HCL

Reinoculate Synbiotics

Repair Supplements

Neurological Evaluation of Autism

Jean-Ronel Corbier, MDPediatric Neurologist

Diplomate of the American Board of Psychiatry and Neurology

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

6 + Categories of NeurodiagnosticEvaluation

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…)

NEUROIMAGING/NEURODIAGNOSTICS CT MRI MRS PET SPECT

Routine EEG Sleep-deprived EEG Prolonged EEG 24 hour video EEG Magnetoencephalograp

hy

Neurometabolic Disorders and Dysfunction in AutismSpectrum Disorders

Nassim Zecavati, MD, MPH, and Sarah J. Spence, MD, PhDCurrent 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

4 Most Common Vegetables in our Children’s Diet

French Fries French Fries French Fries Ketchup

NUTRITIONAL NEUROLOGYDEFICIENCY Dependency,

Interdependency Responsiveness

FOOD Allergy/SENSITIVITY

Vitamin/mineral Vitamin/mineral Immune/food allergy

Cofactors Vitamin/mineral Non-immune

Pyridoxine-dependentepilepsy

Folinic acid responsive Epilepsy

B6-B12-Folate interdependency

Pediatric NeurotransmitterDisease (PND)

-CNS Folate deficiency

Vitamin E deficiency

Creatine deficiency

Biotinidase deficiency

Celiac disease-gluten ataxia

Casein Gluten

Creatine and the BrainThe synthesis of creatine

Symptoms of brain creatine deficiency:-Developmental delay/regression-Mental retardation-Speech delay (usually severe)-Epilepsy-Autism

MRS is the Test of Choice for Detecting and Monitoring Disorders of Creatine MetabolismPediatric Neurology - Volume 40, Issue 5 (May 2009)  -  Copyright © 2009 Elsevier

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) ]

Folate-Responsive Neurologic DiseasesPediatric 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 syndromes2. Normal cerebrospinal fluid and serum folate levels -Folinic acid responsive seizures3. 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

EPILEPSY AND NUTRITION

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

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)  

Celiac DiseaseCrossroad 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

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.

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.

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 

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

FERRITIN AND IRON DEFICIENCY IN AUTISM

Iron Deficiency in Autism and Asperger SyndromeLatif 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

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)

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)

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.

Encephalopathies/Enteropathies/Immunopathies/Psychopathies

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

More on Autism…How Much of a Genetic Basis?

J. Edward Spence, MDCharlotte Ped Society

April 27, 2010

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

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?

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

Genetic Eval of ASDsHistory:

– 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

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

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

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

Genetic Eval of ASDs• Fragile X syndrome

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

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

Genetic Eval of ASDs• Angelman syndrome

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

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

• 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

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

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

THE AUTISMS …AND THE SEARCH FOR MEANINGFUL

SUBTYPES Sarah Spence MD PhD

Pediatrics and Developmental Neuropsychiatry Branch

National Institute of Mental Health

Core Symptom Domains

Social Impairment

Repetitive Behaviors & Restricted Interests

Speech/Communication

Deficits

AUTISMAsperger’s

Adapted from

E.

Hollander

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

Adapted from

E.

Hollander

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

Adapted from

E.

Hollander

Core Symptom DomainsPLUS 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

Adapted from

E.

Hollander

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

Brainmechanisms

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

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 …

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

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

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

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.

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

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