What Children Can Teach Us'''

1
(No Transcript)
2
What Children Can Teach Us...

• Joseph R. Madsen, MD
• Trustee, BrainScience Foundation
• Director, Neurodynamics Lab, Childrens Hospital,
  Boston

3
About Our Meningiomas

• Meningiomas in children are very rare.we have
  time between cases to think about brain dynamics
• Pulsatile dynamics of blood
• Vascular growth factors and the brain (VEGF)

4
How rare?
5
36 cases at Childrens Hospital since 1914 (we
originally found 466 never seen at CH, 4
misdiagnoses
Compare 259 (Cushing and Eisenhardt) 1938 5
were children Dr. Black 733 (reported
2006) BWH database (1980-current ) 1300 cases
6
Meningiomas at CHB

• Gender 50 Male, 50 Female
• Age at presentation (data for 16 patients)
• 1-5 years 3 (8.3) 6-10 yrs
  5 (13.9) 11-15 yrs 6 (16.7) 16-20
  yrs 2 (5.6)
• Median Age 10 yrs

7
Learn from rarities

• "Thus the pathological curiosity of one day
  becomes in its proper time a commonplace... most
  of which are one and the same disorder--had, for
  their interpretation, to await the advent of the
  Neurosurgeon.
• --Cushing and Eisenhardt, Meningiomas,1938

8
If she were an adult, we would know what this
is.
9
Timing, timing, timing

• Meningiomas fall into a later stage in the human
  life cycle
• What can children teach us about the problems we
  have?
• Introduction to Neurodynamics Laboratory Things
  that happen quickly in the brain

10
Time scales

• Risk of meningioma lifespan of human
• Change in cell type years
• Onset of symptoms months
• Brain swelling much faster
• Hydrocephalus faster still
• Migraine seconds
• Seizure seconds

11
Tumor, CSF, vessels

• The tumors, as there is every reason to believe,
  arise from the cell clusters principally
  associated with the arachnoid villi which in
  later life, as Luschka first showed (1852),
  develop into Pacchionian granulations. The
  precise nature of these cells, however, remains
  in dispute.

12
Understanding Brain as a System
13
ICP
Heat rate
Gain
Frequency
14
Designing a Pulsation Absorber

• An engineering problem
• Assume a highly pulsatile input (arterial flow)
• 12 cc in 1/3 second during systole
• Accept a necessary highly pulsatile venous
  outflow
• How to make capillary flow as non-pulsatile as
  possible?

15
Free CSF movement
16
Consequence of blocked CSF movement
17
(No Transcript)
18
(No Transcript)
19
Bulk flow (steady-state dynamics) of hydrocephalus
Putative pulsatile dynamic influences on
hydrocephalus
Increased CSF production
Decreased CSF clearance
By analogy with ocular pathology, could VEGF play
a role in hydrocephalus?
20
Vascular Endothelial Growth Factor VEGF

• Well known receptornew drugs available
• Vascular permeability factor gt10,000x
  histamine potency
• Abundant in choroid plexus

21
Hydrocephalic VEGF Elevation
22
Hydrocephalic VEGF Elevation is Significant
23
Only hydrocephalus?

• Migraine?

24
Soooo

• Insights from far afield (in this case, by age)
  may shed light on the actual clinical problems in
  our patients (and ourselves)
• We cannot prove what we cannot measure, but we
  cannot measure what we can not conceive

25
To keep a young brain, learn from children.
26
Thanks to

• Pedi meningiomas
• Nikki Thuijs
• Mustafa Hameed, MD
• Lolli Fleming
• Dynamics
• Rui Zou, PhD
• Eun-Hyoung Park, PhD
• Tomer Anor, PhD
• Biology
• Simon Shim, PhD
• Nina Irwin, PhD

27
(No Transcript)