Cerebral Palsy

Question 1

What is the aetiology of Cerebral palsy?

Answer 1

There is not one set ‘cause’ etc. There are a set of diff risk factors, characterised by the same phenotype therefore cerebral palsy can be seen as a spectrum disorder.

Linked to: perinatal brain damage often due to traumatic injury such as hypoxia (low levels of oxgen). NB: suffering same injuries past this stage such as in adulthood you cannot get cerebral palsy.

Question 2

Why do we say that cerebral palsy is a non-progressive disease?

Answer 2

Does not get worse with age (symptoms the same) however, growth can bring on new difficulties.

Question 3

What makes researching cerebral palsy hard?

Answer 3

Similar to researching traumatic brain injury: everyone is diff only possible overlap in mechanisms.

Even the same brain injury will cause differential effects on people.

Even if hypoxic as a baby there is no guarantee that you will develop noticable cerebral palsy (severe). The percentage is actually relatively low which thus causes animal research to be both hard and expensive (few cases per thousand).

Question 4

Define placental abruption and state correlation to cerebral palsy

Answer 4

PA: placenta separates from the inner wall of the uterus before birth.

This deprives baby of oxgygen (hypoxic) and found that increases risk 20 fold for cerebral palsy (found to be causitive factor for 26% of cerebral palsy cases in one cohort in Japan = small cohort and diagnosis by physicians could introduce bias).

Question 5

State different risk factors for placental abruption.

Answer 5

Alcohol consumption (i), smoking (i), multiparity (i but small), polyhydramnios (i - too much amniotic fluid), intravenous oxytoxin (d), hypertensive disorder (i).

i = increase
d= decrease

Question 6

State risk factors for cerebral palsy

Answer 6

Ontop of risk factors for placental abruption…

Low birthweight, preterm birth, blood type mismatch, infection or fever during pregnancy, infertility treatments (thought to be due to increased risk of multiparity).

Question 7

What is periventricular leukomalacia and correlation to cerebral palsy?

Answer 7

Perinatal trauma via infection or amniotic rupture that leads to hypo-perfusion of penetrating arteries in brain. Lack of blood flow = lack of oxygen = increased reactive oxygen species in periventricular areas of the brain (NB: this area usually carries messages from brains to muscles).

This damages precursor oligodendrocytes (responsible for CNS myelination) and leads to formation of gliosis scars and tissue damage.
Lipid peroxidation occurs where ROS attack double C-C bond and can lead to death of precursor oligodendrocytes.

This is often accompanies by hemorrhage in periventricular area.

Risk factor as brain damage - cerebral palsy.

Question 8

State reason why oxytoxin may attenuate risk of cerebral palsy

Answer 8

Could be due to continuous foetal heart rate tracing.

Question 9

Define haemolytic disease of the newborn and state the 2 different types.

Answer 9

Immune mediated erythrocyte disorder in which maternal antibodies attack foetal or newborn erythrocytes.

1) ABO incompatability: mothers with O blood have natural A and B antigens so if come in contact with A or B foetal blood will attack: this can happen in first child as antibodies (igG) can cross the placenta (less severe).
2) Rhesus D antigen: foetomaternal hemorrhage causes exposure to foetal blood, maternal antibodies (igM) develops when father has different Rh to mother (rh negative woman and positive foetus is dangerous). First pregnancy is not effected and igM cannot cross placenta. (more severe).

Question 10

How does ABO incompatibility causing haemolytic disease differ from Rh causing and why?

Answer 10

ABO is less severe: possibly due to foetal RBC’s expressing fewer ABO antigens than adults and ABO antigens being expressed by multiple tissues. Prevents specific attack on RBC’s.

Can occur in the first pregnancy as igG can cross the placenta.

Question 11

What does Rh D haemolytic disease often lead to?

Answer 11

Haemolytic anemia: bilirubin is product of RBC breakdown, attack from antibodies causes excess breakdown. Liver cannot breakdown all bilirubin = leads to jaundice, hyperbilirubinemia and kernicterus.

Question 12

Why is haemolytic disease a risk factor for cerebral palsy?

Answer 12

Hyperbilirubin in brain can cause acute brain injuries at micromolar concentrations by aggregating and adhering to cellular membranes, disrupting normal cellular function.
Accumulates in grey matter (triggers apoptosis) and basal ganglia particularly vulnerable to attack.

Question 13

Name the four types of cerebral palsy and give defining symptom

Answer 13

1) Spastic: overly stiff muscles.
2) Dyskinetic/Athetoid: fluctuating muscle tone that cannot be predicted or controlled.
3) Ataxic: motor function deficits (balance, coordination impairments) as well as motor learning and speech difficulties.
4) Mixed: more than one of the above in both symptom and damage.

Question 14

Which type(s) of cerebral palsy known as pyramidal disorder?

Answer 14

Spastic

Question 15

What is the most prevalent type of cerebral palsy and why?

Answer 15

Spastic (80%) due to motor cortex being site of damage.

Motor cortex is the longest route for arteries.

Question 16

Describe symptoms and risk factors of spastic cerebral palsy

Answer 16

Symptoms (develop within the first 2 years): hyper/potonia, limb weakness, tremor, spasms.

Secondary symptoms: acid reflux disease, speech and communication, constipation, learning diff, eyesight and hearing deficiences, spinal curvature abnormal (scoliosis), joint problems.

Risk: Rh mismatch, premature birth, environmental toxins, infection.

Question 17

Which type of cerebral palsy can the motor map be used in and how

Answer 17

Spastic as motor cortex damage: motor map can be used to see what part of the body are impacted.

Question 18

Describe surgery for scoliosis

Answer 18

Grafting put into place to treat abnormal spinal curvature.

Electrophysiological monitoring (reflexes) to ensure no spinal cord damage

Question 19

Define dystonia

Answer 19

Abnormal muscle contractions esp in limbs that causes rotations.

Question 20

Define Athetosis

Answer 20

Slow, sluggish writhing of hands and feet due to basal ganglia damage

Question 21

Define hypertonia

Answer 21

Abnormally high muscle tone that leads to restricted movement.

Question 22

Define Chorea

Answer 22

Involuntary, sudden flowing movements

Question 23

Define ataxia

Answer 23

Loss of co-ordination esp balance, gait eyes or speech.

Question 24

Describe dyskinetic/athetoid cerebral palsy inclu site of brain damage, cause and severity

Answer 24

site: basal ganglia or thalamus.
cause: perinatal trauma such as complex births, kernicterus (as basal ganglia particularly vulnerable).
severity: 75% GMFCS 4/5, more severe than spastic with significant motor or functional disability.

Question 25

How prevalent is dyskinetic/athetoid cerebral palsy?

Answer 25

second most after spastic ~10%

Question 26

Which type(s) cerebral palsy can be classed as extrapyramidal?

Answer 26

dyskinetic/athetoid and ataxic.

Question 27

Describe ataxic cerebral palsy in terms of causes, prevalence, risk, symptoms

Answer 27

Cause: perinatal infection or trauma but can manifest via malformation of cerebellum due to genetic defects (20% of cases due to genetics). CEREBELLAR DAMAGE

Prevalence: 2%

Risk: multiparity

Symptoms: sight problems, eye co-ordination, hearing, common test is to see if child can reach for and touch object.

Question 28

Why does spastic cerebral palsy often impact less of the body than other types?

Answer 28

Spastic is damage to motor cortex, if only small part of one side of brain then hemiplegia.

Other types do not have motor maps.

Of course spastic can impact all body if extent of damage is severe.

Question 29

How is cerebral palsy diagnosed?

Answer 29

Early diagnosis: identify children at high risk for CP and allows for early intervention (less reliable as developmental lag and normal variation).
Below 5 months: MRI and Hammersmith Infant Neurological Examination, approx half children who develop CP have risk factors that allow for this.
Persistance of primitve reflexes: head falls back when picked up, cannot bring hands together at 6 months

Most reliable by 2 years of age: developmental milestones missed, abnormal reflexes (plantar = foot, spastic cerebral palsy show “extensor toe sign”)

Question 30

Outline early interventions that can be applied with early cerebral palsy diagnosis

Answer 30

Constraint-induced movement therapy and enriched home environments.

Question 31

What is the GMFCS and what does it signify

Answer 31

Gross Motor Function Classification System: degree of physical disability (I-V with V most severe).

I: impaired balance and co-ordination.
II: can climb stairs when holding railing, cannot run jump etc.
III: can walk with handheld mobility device
IV: walk short distance or use powered mobility devices.
V: manual wheelchair all settings.

Question 32

How is occupational therapy used in cerebral palsy?

Answer 32

Structured activities performed in hope of improving fine motor control and hand-eye coordination. Usually done whilst ‘playing’ in combo with speech and physical therapy.
Help identify ways to make daily life easier such as development and use of specialised tools.

There is no cure for cp so focused on making daily life easier.

Question 33

How is Baclofen used to help manage cerebral palsy?

Answer 33

Baclofen is GABA B agonist: reduces excitation pre via restriction of calcium influx and post via increase of potassium conductance. Reduces spasticity…

Intrathecal (spinal cord) injection produces higher local concentrations in CSF at fraction of oral dose therefore less sedation.

NB: no correlation found between baclofen intrathecal dosage and baclofen CSF concentration.

Question 34

How is botox used in management of cerebral palsy?

Answer 34

BoNT A: Injected into lower limb to improve stretch and reduce muscle tone, often performed with serial casting. This is not long term.

BoNT A improves passive ankle range of motion. Moderately effective short term and medium term but not significantly more effective than placebo at any time point. Cochrane view found low quality evidence.

Question 35

What is selective dorsal rhizotomy and how is it used to manage cerebral palsy?

Answer 35

Nerve roots in spinal cord severed in spastic mostly performed at lumbrosacral level and consists of interruption of afferent fibres.

Short term improvement in gait and range of motion and long term reduced spasticity.

Question 36

Why may mittens need to be used for some patients with cerebral palsy?

Answer 36

Abnormal sensation may be a complication of cerebral palsy so need to be worn to prevent damage to fingers and hands.

Question 37

What is muscle tendon lengthening and how is it used to manage cerebral palsy?

Answer 37

This is surgically cutting part or all of tendon or muscle to make longer overall.

Range of motion and joint alignment in clinical examination were found to be significantly improved one year after MTL. However, deterioration of these parameters was noted after three years. Similar with muscle tone decrease after one year then subsequent increase in three.

EMG: same after muscle lengthening therefore does not change abnormal muscle pattern activation.

Question 38

Could massages help with management of cerebral palsy?

Answer 38

Cochrane article…

Supplementing marrow and kneading tendon (SMKT) via massages

Test done with control: rehab
SMKT: massage additional to rehab

Greater GMFM-66 improvement seen in SKMT group.
Have to note that no basis for this particular massage has been provided. May be highly biased.

Question 39

What is gastoensophageal disease and how does it relate to cerebral palsy?

Answer 39

Movement of gastric contents up past lower esophagul sphincter which leads to dental erosion, poor weight gain and vomiting.

CP comorbidity due to chronic posture, scoliosis and intra-abdominal pressure from spasticity. Anticonvulsants to manage associated epilepsy increase severity as can cause nausea.

Question 40

What is Nissen fundoplication and how can it be used to manage cerebral palsy?

Answer 40

Wrapping stomach around lower end of esophagus to increase pressure.
NB: Complication rate is higher in children with neurological conditions than general population.

management of Gastroesophageal reflux disease

Question 41

Outline link between epilepsy and cerebral palsy

Answer 41

CP patients who have comorbidity with epilepsy:

69.5% have seizurre within first year of life and average age of onset as 21 months this is significantly earlier in life than control group with 67 months.

Higher proportion of CP epilepsy patients on polytherapy than control (70% vs 17%).

Patients suffering spastic quadriplegia most frequent in epiilepsy at 46%. WIth focal epilepsy most common.

Question 42

Why are animal models of cerebral palsy so hard to make?

Answer 42

As we talked about above this is near impossible: diff aetiologies, people with same damage can show diff symptoms, not everyone with same experience will develop cerebral palsy…
On top of this only a few cases per thousand will lead to cerebral palsy

Question 43

Outline a genetic model for cerebral palsy.

Answer 43

Glycine receptor mutation = reduced glycinergic transmission. assessed when mice over 4 weeks old.

Abnormal gait, hypertonia, exaggerated startle

Question 44

Outline an animal model of hypoxia/ischemia for cerebral palsy

Answer 44

Model :rat
Occulsion of uterine arteries at 86% gestation.

Decreased stride length.
Glial activation, white matter injury and cell death in cortex.
Decreased inhibitory synaptic currents in hippocampus.

Question 45

Why are some animal models of cerebral palsy based on hypoxia?

Answer 45

Hypoxia/ischemia most common perinatal brain injury.

NB: controversial as delivery of oxygen after trauma shown to not impact outcome.

Question 46

Outline model of inflammation/toxin for cerebral palsy.

Answer 46

IP injection of bacterial endotoxin.

More movement in open field test, altered gait. Infarct (dead due to loss of blood supply) of cerebral cortex, hippo. Activated glia and white matter injury.

Question 47

Outline how cerebral palsy and neurogenesis are linked.

Answer 47

Perinatal brain damage impairs neurogenesis during critical period of development.

Oxygen deprivation: altered cell proliferation

Inflammation and hemorrhage: variable results in relation to proliferation, migration and differentiation up to adulthood.

Prenatal brain damage = reduces number of neural stem cells.

Postnatal: increased proliferation of neural precursor cells, reduced survival of newly created neurons.

Differential proliferation in males and females that makes males more susceptible.

Question 48

Outline theory of neurogenesis and cerebral palsy

Answer 48

Neurogenic niches: specific brain areas neurogenesis occurs in such as subventricular zone.

progenitors that migrate postnatally from neurogenic niches in response to injuries in most cases either become interneurons or glial cells or do not survive in the long term. Would normally develop into interneurons.

Furthermore microglia enhance neural stem cell proliferation and migration to injured area.