Child Neurology

Question 1

child neurology vroeger vs nu

Answer 1

meer kinderen krijgen een diagnose, meer collaboration en meer treatments

Question 2

in nederland

Answer 2

elk centra heeft zijn eigen focus

Question 3

amsterdam..

Answer 3

white matter disorders -> inherited leukodystrophies, neonatal and spasticity

Question 4

leukodystrophies…

Answer 4

genetic disorders -> defect in the genes involved in the maintainance and growth of myelin. age of onset: infancy-adulthood. main tool for diagnosis is MRI

Question 5

white matter is…

Answer 5

de axonen van neuronen, glia cellen etc.

Question 6

difficulties with research in children

Answer 6

• ethical issues
• communication with the children
• still under development: ziekte die rond 2 jaar opkomt is compleet anders dan dezelfde ziekte rond 4 jaar

Question 7

the brain myelinates within…

Answer 7

the first 2 years

Question 8

neonatal white matter…

Answer 8

low t1 signal, high t2 signal

Question 9

myelinated white matter…

Answer 9

high t1 signal, low t2 signal

Question 10

t2 is sensitive for high/low myelin

Answer 10

low

Question 11

dus je kan HM goed zien via…

Answer 11

t2, want hier is myelin amount low en dit vang je goed op met een t2. hier is het myeline donkerder. Bij een t1 is het myeline lichter, hiermee kan je goed myeline zien in non-ms patienten

Question 12

hoe zie je HM dus op een t2 mri scan?

Answer 12

hyperintensitivity! dus heel fel

Question 13

hypomyelination symptomen

Answer 13

• nystagmus -> oogafwijking, dat ze heel snel heen en weer gaan
• wheelchair dependency
• spasticity, mixed movement disorder
• ataxia -> onregelmatige en onhandige bewegingen van de romp en ledematen
• mental redartation
• reduced life expectancy

Question 14

genetic predisposition hypomyelination

Answer 14

plp1 alteration, minder abundant myelin protein

Question 15

de clinical presentation van hypomyelination verschilt heel erg!

Answer 15

oke

Question 16

wat is de biologische afwijking van HM van de ziekte?

Answer 16

myeline loss, daardoor worden axonen niet meer beschermd en kunnen deze dus aangetast worden (conduction, protection, nutrients)

Question 17

3 reserach questions

Answer 17

• what are the genetic causes?
• what is the basis of the clinical variability between patients?
• explanation for decline after years of stable disease?

Question 18

HS is niet hetzelfde als MS!!!

Answer 18

dit gaat namelijk om loss of a protein. Bij multiple sclerosis wordt het zenuwstelsel aangevallen.

Question 19

hypomyelination with brainstem and spinal cord involvement and leg spasticity is caused by mutations in..

Answer 19

DARS

Question 20

het is een..

Answer 20

autosomal recessive disesase

Question 21

DARS encodes..

Answer 21

a tRNA synthetase

Question 22

waar zit de hypomyelination vooral in HBSL

Answer 22

brain stem

Question 23

waar staat HBSL voor

Answer 23

hypomyelination with brain stem and spinal cord involvement and leg spasticity

Question 24

wie maken myeline in CNS

Answer 24

oligodendrocytes

Question 25

wie maken myeline in PNS

Answer 25

schwann cells

Question 26

metachromatic leukodystrophy

Answer 26

MLD, lysosomal storage disorder, autosomal recessive

Question 27

wat is de disease pathology van MLD

Answer 27

weinig arylsulfatase a -> accumulation of sulfatides in membranes of myelin. dit enzym zorgt voor demyelination.

Question 28

verschilllende soorten onset

Answer 28

late infantile (< 30 months) juvenile (30 months-16 years) adult (16 years or older)

Question 29

early onset symptomen

Answer 29

motor symptoms, rapid progression

Question 30

late onset

Answer 30

cognitive symptoms

Question 31

diagnosis:

Answer 31

dots and later on in life atrophy

Question 32

treatment options

Answer 32

- allogenic hematopoietic stem cell transplantation. dan krijgen ze chemo en daarna transplantation of donor cells die weer productie en secretie van ASA. kan maar bij 1/3 van de patienten. - ex vivo gene therapy - intrathecal enzyme replacement ERT

Question 33

ex vivo gene therapy

Answer 33

overexpression of arylsulfatase a in modified macrophages -> effective bij jonge kidneren

Question 34

intrathecal enzyme replacement ERT

Answer 34

asa injection into the CSF.

Question 35

what have we learned from MLD?

Answer 35

ØThere are markers helping decide whether or not it is too late for transplantation (IQ, NAA).ØMLD has variants with only mildly affected motor function and no/mild neuropathy (depending on the mutations in the ARSAgene).ØTransplantedbonemarrow cells migrate to the brain and produce arylsulfatase A there, but this is not taken up by brain cells.ØTransplanted bone marrow cells have an anti-inflammatory neuroprotective effect.ØRemyelination after transplantation is possible.ØGrey matter is not (sufficiently) targeted by transplantation.