cost efficient eval of a child with neurodevelopmental disabilities-ndd january 2014 (10)

8/12/2019 Cost Efficient Eval of a Child With Neurodevelopmental Disabilities-NDD January 2014 (10)

1/32

Cost Effective Evaluation of a Child WithNeurodevelopmental Disabilities (NDD)

Kenton R. Holden, M.D.

Professor of Neurosciences (Neurology) & PediatricsMedical University of South Carolina

Charleston, South Carolina

Senior Clinical Research NeurologistGreenwood Genetic CenterGreenwood, South Carolina

Tegucigalpa, Honduras

January 31, 2014


2/32

Neurodevelopmental Disabilities (NDD)

Disclosures:1. NIH Funding R01s re: ID Etiologies 2010-15, and

Neuronal Gene Regulatory Elements with Epilepsy2012-2016.

2. Smile Foundation: Co-PI for Pilot Funding 2013-2014;Assessment of Brain Structures and Tracts in X-LinkedMCT8 Gene Abnormalities Using MRI.

3. Pediatric Neurology Consultant at the GreenwoodGenetic Center, Greenwood, SC.

4. My favorite canvas briefcase was given to me at AES2000 by Abbott Labs (Depakote / Depakene).

Holden K 01/31/14


3/32


I. Characteristics:

A. Common problem: About 100,000 born/yr;

2 to 3% of all children < 6-yrs-old

B. Etiologies heterogeneous, but childrens delayssimilar - many of whom have intellectualdisabilities (ID)

C. Chronic disorder without prolonged plateauor regression in skillsD. Frequent referral to Pediatrics, Neurology, & Genetics

Holden K 01/31/14


4/32


I. Graphic Representation of Childhood Development

(A)5

4

Developmental 3Skills

(Years)

2

1

1 2 3Chronological Age (Years)

(B)

(C)

(D)

(E)

4 5

Holden K 01/31/14


5/32


I. Characteristics: (continued)A. Cognition

NOTE: Many reports use IQ [or developmental quotient (DQ)] of 50-69 as mildimpairment, and IQ or DQ


6/32


I. Characteristics: (continued)

A. Significant documented disturbance in two ormore developmental domains( 2 std. dev. below the mean for age)

Cognitive (intellect)

Motor (gross and/or fine)

Speech/languageBehavioral/Social

Activities of daily living

Holden K 01/31/14


7/32


I. Characteristics Summary:

A. DOMAINS:

Single: Cognitive / intellectual disability (ID)...formerly mental retardation (MR);

gross motor delay / cerebral palsy (CP)Multiple: Neurodevelopmental disabilities (NDD)

B. FINAL DIAGNOSIS relies on a careful and detailed history(pedigree), observational and direct examination (OFC,fundi, etc.), appropriate psychological testing, andlaboratory investigations.

C. SECOND VISIT is an integral part of the diagnostic

assessment.Holden K 01/31/14


8/32


II. Why Evaluate? (mostly Class III evidence,lack of therapies, low yield, availability,invasiveness, costs, etc.)

A. Treatments are evolvingB. Prognosis is evolving

C. Management of related disorders

D. Risk of reoccurrence (screening)

E. Limits additional unnecessary testing

F. Empowers family to plan, network, etc.Holden K 01/31/14


9/32

Summary: Neurodevelopmental Disabilities (NDD)1. Obtain a detailed history and examination (...includes birth/neonatal OFC & current OFC)

2. Refer for auditory and ophthalmologic screening

3. Consider metabolic studies/T4if universal newborn screening not done.

4. If history of suspected seizures or epilepsy syndrome, obtain EEG

5. Consider screening for a language disorder or autism

6. Is there a close family member with NDD (e.g., sibling, aunt/uncle, first cousin, etc.):

A. Due to a known metabolic, genetic, or structural nervous system disorder?

B. Unexplained NDD?

(A.)/(B.)---- Yes(A.) Obtain specific test(s)

for that disorder

(B.) Obtain microarrayand Fragile X

(A.)/(B.) ---- No

7. Are there features suggesting a specific diagnosis?

If tests C. Are there historical or physical findings (e.g. dysmorphic features) to

are (-) suggest Down, Fragile X, Rett syndrome, other neurogenetic disorders, or

hypothyroidism?

D. Are there historical (intrapartum asphyxia, neurobehavioral, etc.), orphysical findings (microcephaly, cerebral palsy, focal findings), or

seizures (infantile spasms (IS); partial) to suggest CNS injury ormalformation?

E. Does the child have any identifiable risk factors for excessiveenvironmental/lead/other exposure as per established current guidelines?Yes No (F.) but plateau and/or regression in milestones evident

(C.) (D.)

Specific Brain MRI

test(s) for preferred

that to CT scandisorder

(E.)

Blood

Lead

level,

etc.

(F.)

Stepwise evaluations forNeurodegenerative

Disease.

Holden K 01/31/14


10/32


III. Evaluation

1. Obtain a detailed history & exam; however, not allNDD genetic d/o have syndromic FHx or exam.

2. Auditory and ophthalmologic screening

3. Metabolic studies, T4/TSH if universalnewborn screening not done

4. EEG only if history of suspected seizuresor an epileptic syndrome5. Screen for autism prn

NOTE: No single set of laboratory tests is indicated

in all cases. Holden K 01/31/14


11/32


Electroencephalography:

Holden K 01/31/14


12/32


III. Evaluation: (continued)

A. If close family relative with NDD due to

known cause, obtain specific test (plasmaamino acids, lactate / pyruvate, ammonia,ceruloplasmin, transferrin, urine organicacids, Fragile X)

B. If close family relative with NDD due tounexplained cause, obtain a microarrayand Fragile X.

Holden K 01/31/14


13/32


III. Evaluation: (continued)

C. Are there features suggesting a specificdiagnosis?Are there significant historical or physical

findings, e.g. Down, Fragile X, Rett,Angelman, other neurogenetic d/o,hypothyroidism, etc.?...then obtainspecific test.

Holden K 01/31/14


14/32


Dx: ?? Dx: ?? Dx: ??

Holden K 01/31/14


15/32


16/32


Dx: ?? Dx: ?? Dx: ??

Holden K 01/31/14


17/32


Dxs: Fragile XHolden K 01/31/14


18/32


III. Evaluation: (continued)D. Are there features suggesting a specific

diagnosis?

Are there historical (intrapartum,

neurobehavioral, etc.) or physicalfindings (microcephaly*, CP, focalfindings) or epilepsy [Infantile Spasms

(IS); partial sz] to suggest brain injury ormalformation?...then obtain brain MRI(preferred to CT).

*Reference #8: Rollins, JD et al., J Peds 2010;156:907 Holden K 01/31/14


19/32


2 mo old HM with NDD and IS

Dx: ??Holden K 01/31/14


20/32


Dx: MSUD Holden K 01/31/14


21/32


2 yo WF with NDD &partial epilepsy

Request MRIs: ??DX: ??

5 yo WM with NDD& partial epilepsy

Holden K 01/31/14


22/32


T1-sagittalDx: ??

T1-axial

Holden K 01/31/14


23/32


2 yo WF 5 yo WMNDD & partial epilepsy NDD & partial epilepsy

T1-sagittal T1-axial

Dx: Epidermal Nevus syndrome Holden K 01/31/14


24/32


III. Evaluation: (continued)E. Does the child have any identifiable risk

factors for excessive environmental exposures,infections, etc., per established guidelines?

If identifiable, obtain iron, lead, HIV testing,etc., prn.

Holden K 01/31/14


25/32

Summary: Neurodevelopmental Disabilities (NDD)1. Obtain a detailed history and examination (...includes birth/neonatal OFC & current OFC)

2. Refer for auditory and ophthalmologic screening

3. Consider metabolic studies/T4if universal newborn screening not done.

4. If history of suspected seizures or epilepsy syndrome, obtain EEG

5. Consider screening for a language disorder or autism

6. Is there a close family member with NDD (e.g., sibling, aunt/uncle, first cousin, etc.):

A. Due to a known metabolic, genetic, or structural nervous system disorder?

B. Unexplained NDD?

(A.)/(B.)---- Yes

(A.) Obtain specific test(s)for that disorder

(B.) Obtain microarrayand Fragile X

(A.)/(B.) ---- No

7. Are there features suggesting a specific diagnosis?

If tests C. Are there historical or physical findings (e.g. dysmorphic features) to

are (-) suggest Down, Fragile X, Rett syndrome, other neurogenetic disorders, or

hypothyroidism?

D. Are there historical (intrapartum asphyxia, neurobehavioral, etc.), orphysical findings (microcephaly, cerebral palsy, focal findings), or

seizures (infantile spasms (IS); partial) to suggest CNS injury ormalformation?

E. Does the child have any identifiable risk factors for excessive

environmental/lead/other exposure as per established current guidelines?

Yes No (F.) but plateau and/or regression in milestones evident

(C.) (D.)

Specific Brain MRI

test(s) for preferred

that to CT scandisorder

(E.)

Blood

Lead

level,

etc.

(F.)

Stepwise evaluations forNeurodegenerative

Disease.

Holden K 01/31/14


26/32

III. Evaluation : F. Evaluation of Neurodegenerative Disorders of Childhood with Cognitive Decline (Dementia)

(1) Screen for disorders that are potentially treatable orhave genetic implications - Rule out:

Yes

(A) Systemic Illness or Intoxicant (C) Hypothyroidism(B) Increased Intracranial Pressure (D) Metabolic Disease

No YesVisceromegaly? Abnormalities ofSkin and / or Hair

No

Elements of Hurler Brain MRI with Brain MRI with Eye

(12) Menke Disease(13) Fabry Disease

(14) Biotinidase Deficiency(15) Cockayne Syndrome Type I(16) Cerebrotendinous Xanthomatosis

(17) Glycosylation Disorders

Dysmorphic ? Yes

No

Urine Screen forReducing Substances

Positive

Phenotype

No

(7) Disorders of Peroxisomal BiogenesisZellweger Syndrome

Neonatal Adrenoleukodystrophy

Yes

Urine Screen forMucopolysaccharides

NoDemyelination orDysmyelination?

Yes

Macrocephaly?Yes

of the Tiger Sign? No

Yes

(28) PantothenateKinase-AssociatedNeurodegeneration

Yes

Brain MRI with SymmetricalLesions in Basal Ganglia /Thalamus / Brainstem

No

OphthalmologyConsult

Negative

(2) Galactosemia(3) Fructose Intolerance

Bone MarrowAspirate For

Gaucher Cells

Infantile Refsum Disease

Positive

(8) Mucopolysaccharidosis

Negative

Urine Screen forOligosaccharides

Negative

No (18) Alexander Disease(19) Canavan Disease

Microcephaly?Yes

No

(1) Organic / Amino Acid Disorders

(14) Biotinidase Deficiency(23) Mitochondrial Disorders

(Leigh Syndrome, etc.)

(29) Huntington Disease(30) Wilson Disease

NoPathology Pathology

See Table 2

Seizures asPositive

MPS I - HurlerMPS II - Hunter

MPS III - Sanfilippo Positive

(20) AcquiredImmunodeficiencySyndrome

ProminentSymptom?

(4) Gaucher DiseaseNegative MPS VII - Sly (11) Mucolipidosis II

Multiple Sulfatase Deficiency Seizures as

Yes Prominent Symptom?

(9) OligosaccharidosisMannosidosis I (17) Glycosylation Disorders No

No

Yes

(23) Mitochondrial Disorders(31) Lesch-Nyhan Syndrome(5) Sandhoff Disease

(6) Niemann-Pick Disease Fucosidosis ISialidosis IIGalactosialidosis

(10) GM1Gangliosidosis Type I

(21) Krabbe Disease(22) Subacute Sclerosing

Panencephalitis (SSPE) (23) Mitochondrial Disorders

(23) Mitochondrial Disorders (24) Pelizaeus-Merzbacher Disease(25) Metachromatic Leukodystrophy

(26) Adrenoleukodystrophy(27) Leukoencephalopathy with

Vanishing White Matter

(17) Glycosylation Disorders

(23) Mitochondrial Disorders(29) Huntington Disease(32) Rett Syndrome

(33) GM1GangliosidosisType II

See Reference #7: Goldstein EM, Holden KR, Chapter 51 in Maria BLs text book, 2009. Holden K 01/31/14


27/32

Neurodevelopmental Disabilities (NDD)References:

1. Shevell M, et al: Practice parameter: evaluation of the child with global developmental delay.Neurology 2003; 60:367-380.

2. Shaffer LG: American College of Medical Genetics guideline on the cytogenetic evaluation of the

individual with developmental delay or mental retardation. Genetics in Medicine 2005; 7:650-654.

3. Moeschler JB, Shevell M, and the Committee on Genetics: Clinical Genetic Evaluation of the ChildWith Mental Retardation or Developmental Delays. Pediatrics 2006; 117:2304-2316.

4. Paciorkowski AR and Fang M: Chromosomal microarray interpretation: What is a child

neurologist to do? Pediatr Neurol 2009; 41:391-398.

5. Ashwal S, et al: Practice Parameter: Evaluation of the child with microcephaly (an evidence-basedreview). Neurology 2009; 73:887-897.

6. Holden KR and Lyons MJ: Chapter 62, Microcephaly-Acquired. In: Maria BL, ed. Current

Management in Child Neurology. 4th Edition. Shelton, CT: PMPH/BC Decker, Inc, 2009:421-428.

7. Goldstein EM and Holden KR: Chapter 51, Neurodegenerative Disorders. In: Maria BL, ed. Current

Management in Child Neurology. 4th Edition. Shelton, CT: PMPH/BC Decker, Inc, 2009:322-336.

8. Rollins JD, Collins JS, and Holden KR: US head circumference growth reference charts: Birth to 21years. Jour Pediatr 2010; 156:907-913.

9. Michelson DJ, et al: Evidence Report: Genetic and metabolic testing on children with globaldevelopmental delay. Neurology 2011; 77:1629-1635.

Holden K 01/31/14


28/32

Holden K 01/31/14


29/32

Holden K 01/31/14


30/32

Holden K 01/31/14


31/32

Holden K 01/31/14


32/32


Acknowledgements:

1) Patti Broome & Suzan White, Admin Assts. at GGC.

2) All my patients, their parents, and my instructors forteaching me the ever evolving subject of childhoodNDD.

Thank you!

Questions???Holden K 01/31/14

cost efficient eval of a child with neurodevelopmental disabilities-ndd january 2014 (10)

Documents