Abnormal Corpus Callosum Morphology in Congenital Hypothyroidism - - PowerPoint PPT Presentation

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Abnormal Corpus Callosum Morphology in Congenital Hypothyroidism - - PowerPoint PPT Presentation

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Abnormal Corpus Callosum Morphology in Congenital Hypothyroidism Joanne Rovet, Farhana Islam, Arash Samadi, Jovanka Skocic A MERICAN T HYROID A SSOCIATION A NNUAL M EETING S AN J UAN P UERTO R ICO , O CTOBER 2013 PRESENTATION FROM THE 83rd

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Abnormal Corpus Callosum Morphology in Congenital Hypothyroidism

AMERICAN THYROID ASSOCIATION ANNUAL MEETING SAN JUAN PUERTO RICO, OCTOBER 2013

Joanne Rovet, Farhana Islam, Arash Samadi, Jovanka Skocic

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Disclosure

I have nothing to disclose

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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SLIDE 3

Corpus Callosum

  • Largest white matter

(WM) tract in brain

  • Transfers information

between hemispheres

  • Needed for many

functions (e.g., bimanual coordination, social communication, complex reasoning)

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Corpus Callosum

Hofer & Frahm (2006) NeuroImage 32:989-994

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Corpus Callosum Abnormalities

Raybaud, C. (2010) Neuroradiol 52:447-477

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Corpus Callosum Abnormalities

fetal alcohol syndrome Turner syndrome ADHD prematurity autism

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Corpus Callosum Abnormalities

  • Down syndrome
  • Williams syndrome
  • 22q11.2 syndrome

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Berbel P et al (1994) Behav Brain Res 64: 9-14

Thyroid hormone is essential for corpus callosum development

Powell M.H. et al (2012) Neurotoxicol 33: 1322-1329

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Thyroid hormone is essential for corpus callosum development

wild type

Pettigrew, R., et al (2007) Vet Pathol 44:50-56

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • Undergoes major development in

gestation and postnatally

  • period of exuberant axonal growth
  • bidirectional & inside-out pattern
  • anterior before posterior

Corpus Callosum Development

20 wk 13 wk 12 wk 14 wk 30 wk

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • Undergoes major development in

gestation and postnatally

  • period of exuberant axonal growth
  • exuberant axonal pruning
  • myelination

Corpus Callosum Development

20 wk 13 wk 12 wk 14 wk 30 wk

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • Undergoes major development in

gestation and postnatally

  • period of exuberant axonal growth
  • exuberant axonal pruning
  • myelination

Corpus Callosum Development

20 wk 13 wk 12 wk 14 wk 30 wk

Is corpus callosum development affected in congenital hypothyroidism (CH)?

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • Experience a circumscribed period
  • f thyroid hormone deficiency
  • reflects etiology, severity of

hypothyroidism at diagnosis, treatment factors (age, dose)

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • 1. Is corpus callosum morphometry and

morphology affected in congenital hypothyroidism (CH)?

  • 2. Are corpus callosum abnormalities

associated with disease severity and treatment?

  • 3. Are effects correlated with

(suboptimal) outcome?

3 Research Questions

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • N=41
  • 9 to 16 yrs (mean=12.4 yrs)
  • 11 athyrosis, 21 ectopic,

6 dyshormonogenesis, 3 unknown

  • Median Rx onset=13 days
  • Median TSH@diagnosis=311

mU/L

  • Mean T4@diagnosis=53.9+36.2

nmol/l

Sample: CH

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Sample: Controls

  • 42 youth matched with CH for:
  • age (mean=12.0 yrs)
  • sex
  • socioeconomic status

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • Day 1: 4-hour

neuropsychological evaluation

  • Day 2: 1-hour MRI scan in 1.5

Tesla magnet

  • 7-min axial T1 FSPGR

sequence (TR/TE=10.3/4.2 ms,

inversion time=400 ms, flip angle = 200, slice thickness = 1.5mm)

  • Corpus callosum manually

traced and measured using Analyze 9.0

Procedures

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Quantitative Approach

genu splenium

rostrum

isthmus anterior midbody posterior midbody

genu splenium Hofer & Frahm (2006) NeuroImage 32:989-994

VI

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Quantitative Approach

genu splenium

rostrum

isthmus anterior midbody posterior midbody

genu splenium

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • Curvature (d)
  • Droop (e)
  • Peak (a)

Qualitative Approach

Gabrielli O et al (1993) Neuroradiol 35:109-112

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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  • Shape (“bulbosity”) of genu (A/B) and

splenium (C/D)

Qualitative Approach

A B C D

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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CH have smaller genus

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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CH have narrower genus

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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CH show abnormal shape

Control CH

  • Flatter corpus callosum,

p<0.001

  • Less droop in splenium,

p=0.017

  • No difference in peak of

genu

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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CH show “more bulbous” genus

genu

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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CH show normal spleniums

splenium

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Question 2: Is CC Morphometry Associated with Early Disease Factors?

  • No effect of TSH or T4 levels at diagnosis, age
  • f treatment onset, starting dose LT4
  • Genu smaller in athyrosis &

dyshormonogenesis vs ectopic etiology

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Question 3: Is CC size associated with specific abilities?

isthmus anterior midbody genu splenium

Genu & anterior midbody size highly correlated with IQ

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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In Summary

  • Youth with CH show:
  • Reduced size and width of CC genu
  • Less curvature, abnormal orientation
  • f splenium, more bulbous genu
  • More severe CH at diagnosis associated

with reduced size of genu

  • Reduced size of certain CC regions

predictive of specific cognitive weaknesses

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Conclusion

  • Despite the current optimal care of

congenital hypothyroidism, persisting residual cognitive deficits may still arise from corpus callosum abnormalities associated with early thyroid hormone insufficiency

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)

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Arash Samadi Farhana Islam Jovanka Skocic

Thank You

PRESENTATION FROM THE 83rd ANNUAL MEETING OF THE AMERICAN THYROID ASSOCIATION, OCTOBER 16-20, 2013 (Joanne Rovet)