Oncology, Neurology Flashcards
How is childhood cancer classified?
ICCC (International classification of childhood cancer)
Based on tumour morphology (cell origin) and primary site
Standard classification is essential for comparing incidence & survival across regions & time periods
When are children more likely to get cancer?
At a younger age (0-4yo)
15-24 yo = another peak as they have an increased risk of germ cell tumours and lymphomas
In 10% what are possible causes that may be identified for cancer?
- Genes (Down, Fanconi, BWS, Li-Fraumeni familial cancer syndrome, neurofibromatosis)
- Environment (radiation, infection(e.g. EBV))
- Iatrogenic (RT, chemo)
Is child cancer sporadic?
Usually yes but it is important to ask about risk factors
What makes the categories for referral in child cancer?
IMMEDIATE=unexplained petechiae, hepatosplenomegaly
URGENT=repeated attendance, same problem, no clear diagnosis OR new neuro symptoms, abdo mass
REFER (to doctor or for urgent investigation)=rest pain, back pain & unexplained lump, lymphadenopathy
What are some examples of oncological emergencies?
- Sepsis/febrile neutropenia
- Raised ICP
- Spinal cord compression
- Mediastinal mass
- Tumour lysis syndrome
What are risks for sepsis/febrile neutropenia?
ANC< 0.5 x10 to the 9
Indwelling catheter
Mucosal inflam
High dose chemo/SCT
How do those with sepsis/febrile neutropenia present?
- Fever (or low temp)
- Rigors
- Drowsiness
- Shock (metabolic acidosis)
If child is not responding to simple measures and has significant shock sometimes they need ionotropic support to help their BP, transferred to PICU
What is the early presentation of raised ICP?
- Early morning headache/vomiting
- Tense fontanelle
- Increasing HC (head circumference)
What are the signs of late presentation of raised ICP?
- Constant headache
- Papilloedema
- Diplopia (VI palsy)
- Loss of upgaze
- Neck stiffness
- Status epilepticus
- Reduced GCS
- Cushing’s triad (low HR, high BP, falling RR)
What is the investigation for raised ICP?
Imaging mandatory if safe
CT is good for screening
MRI is best for more accurate diagnosis
What is the management of raised ICP?
DEXAMETHASONE if due to tumour (reduce oedema & increase CSF flow)
NEUROSURGERY-urgent CSF diversion
- Ventriculostomy-hole in membrane at base of 3rd ventricle with endoscope
- EVD (temporary)
- VP shunt
In whom is spinal cord compression more common (potential complication of nearly all paed malignancies)?
Ewing’s or Medulloblastoma
When does spinal cord compression arise and what is the pathological process of it?
Diagnosis of cancer(65%), relapse, progression
- Invasion from paravertebral disease via intervertebral foramina (40% extradural)
- Vertebral body compression (30%)
- CSF seeding
- Direct invasion
What is the presentation of spinal cord compression?
Symptoms vary with level
- WEAKNESS
- PAIN
- SENSORY
- SPHINCTER DISTURBANCE
How is spinal cord compression managed?
- URGENT MRI
- Start DEXAMETHASONE urgently to reduce peri-tumour oedema
- Definitive treatment with chemo is appropriate when rapid response is expected (surgery or RT are other options)
What does the outcome of spinal cord compression depend on?
- Severity of impairment rather than the duration between symptoms and diagnosis
(Mild impairment >90% recovery, Paraplegic 65% recovery)
SVC syndrome (or SMS) is rare (<1% of new paediatric malignancies): what are the common causes of it?
- LYMPHOMA
- Other=neuroblastoma, germ cell tumour, thrombosis
How does SVC syndrome and SMS present and how is it investigated?
SVCS: facial, neck and upper thoracic plethora, oedema, cyanosis, distended veins, ill, anxious, reduced GCS
SMS: dyspnoea, tachypnoea, cough, wheeze, stridor, orthopnoea
Investigation:
CXR / CT chest (if able to tolerate)
Echo
What is the management of SVCS and SMS?
Keep upright & calm
Urgent biopsy (ideally)
Look to obtain important diagnostic information without GA
FBC, BM, pleural aspirate, GCT markers
Definitive treatment is required urgently:
- Chemotherapy is usually rapidly effective
- Presumptive treatment may be needed in the absence of a definitive histological diagnosis (steroids)
- RT is effective (May cause initial increased respiratory distress)
- Rarely surgery if insensitive
- CVAD-associated thrombosis should be treated by thrombolytic therapy
Most of underlying malignancies have a good prognosis
What is tumour lysis syndrome caused by?
Metabolic derangement
Rapid death of Tumour Cells
Release of intracellular contents
At or shortly after presentation
Secondary to treatment
(rarely spontaneous)
What are the clinical features of tumour lysis syndrome?
INCREASED potassium, urate-relatively insoluble, phosphate
REDUCED calcium
Acute renal failure:
Urate load
CaPO4 deposition in renal tubules
What is the treatment of tumour lysis syndrome?
Avoidance
ECG Monitoring
Hyperhydrate-2.5l/m2
QDS electrolytes
Diuresis
NEVER GIVE POTTASIUM (or phosphate)
Decrease uric acid:
- Urate Oxidase-uricozyme (rasburicase)-acute setting
- Allopurinol
Treat hyperkalaemia:
Ca Resonium
Salbutamol
Insulin
Renal replacement therapy
What do oncologists use to see what cancer is and what harm it is causing?
- Scans
- Biopsy/pathology
- Cytogenetics
- Tumour markers
What tumours can secrete AFP?
Liver tumours or germ cell tumours
Can be diagnostic
How is cancer staged?
Staging-e.g. scans, bone marrow
CXR or CT chest
Bone scan
Number of different tests depending on what’s the primary tumour and the location of the primary tumour
What is cannonball metastases in the chest typical of?
Sarcoma diagnosis-indicate very poor prognosis
What does treatment of cancer depend on?
Multimodal therapy based on specific disease and extent (plus patient factors)
MDT approach
National/international collaboration
Clinical research
How does a bone marrow transplant work?
Collect STEM cells from somebody else and put
them back into a new patient where they will travel to the bone marrow and then set up a completely new immune system.
Bone marrow transplants allow you to use very high dose chemotherapy but they also give you an immune response where the donor immune system will recognise the host cancer cells as foreign and kill them using the same kind of approach as immunotherapy.
What are the acute risks of chemo?
Hair loss
Nausea & vomiting
Mucositis
Diarrhoea / constipation
Bone marrow suppression – anaemia, bleeding, infection
What are the chronic risks of chemo?
Organ impairment – kidneys, heart, nerves, ears
Reduced fertility
Second cancer
What are the acute and chronic risks of RT?
Acute:
Lethargy
Skin irritation
Swelling
Organ inflammation – bowel, lungs
Chronic:
Fibrosis / scarring
Second cancer
Reduced fertility
Survivors of childhood cancer have … toxicity
ACCUMULATIVE
(from being treated with childhood cancer)
How so is child neurology dynamic?
Brain continues to grow and brain functions evolve
Neurodevelopment continues to progress
Static lesion produce evolving features
Why is time course of symptoms crucial in a neurological condition?
To ascertain symptom progression - and to try to determine a differential diagnosis
Distinguishing static from slowly progressive symptoms can be challenging
What is crucial to ask in a developmental Hx?
- Motor milestones (gross and fine motor skills)
- Speech and language development
- Play esp symbolic play and social behaviour
- Self help skills
- Vision and hearing assessment
Global delay=if delayed in 2 or mote of these domains
Disordered development=1 of these fields
What is included in the neurological examination in childhood?
- Opportunistic approach and observation skills
- Appearance
- Gait
- Head size
- Skin findings (neurocutaneous markers (e.g. Cafe au lait spots—neurofibromatosis, Port wine stain—Sturge Weber syndrome)
What neurological conditions are seen (examples)?
Migraine
Traumatic brain injury
Tourette syndrome (1% of all children with high frequency in ADHD & OCD)
Epilepsy
Brain tumours (2nd most common cancer in children)
What are the categories of headache a child can have?
- Isolated acute
- Recurrent acute
- Chronic progressive
- Chronic non-progressive
How would you classify a chronic headache?
Patient suffers from a sore head for at least 15 days out of 30 days in a month
What should be included in a recurrent or chronic headache Hx?
- Is there more than 1 type of headache
Typical episode
- Any warning
- Location
- Severity
- Duration
- Frequency
What should be included in a headache examination?
- Growth parameters, OFC, BP (HT can be a signal of intracranial pathology but can also itself cause headaches)
- Sinuses, teeth, visual acuity
- Fundoscopy
- Visual fields (craniopharyngioma)
- Cranial bruit
- Focal neurological signs
- Cognitive and emotional status
The diagnosis of headache etiology is clinical
What pointers would point you towards childhood migraine?
Hemicranial pain - throbbing/pulsatile
Associated abdominal pain, nausea, vomiting
Focal symptoms/ signs before, during, after attack: Visual disturbance, paraesthesia, weakness (AURA)
‘Pallor’
Aggravated by bright light/ noise (Photophobia/phonophobia)
Relation to fatigue/ stress
Helped by sleep/ rest/ dark, quiet room
Family history often positive
What pointers would make you think of a tension headache (as apposed to migraine)?
- Diffuse, symmetrical
- Band like distribution
- Present most of the time (but there may be symptom free periods)
- ‘constant headache’
Pointers to raised ICP (Red flags)?
Aggravated by activities that raise ICP eg. Coughing, straining at stool, bending
Woken from sleep with headache +/- vomiting
What presentation features would make you think of analgesic overuse headaches?
Headache is back before allowed to use another dose
Paracetamol/ NSAIDs
Particular problem with compound analgesics eg. Cocodamol
In headache what are the indications for neuroimaging?
Features of cerebellar dysfunction
Features of raised ICP
New focal neurological deficit eg. new squint
Seizures, esp focal
Personality change
Unexplained deterioration of school work
How is migraine managed (Acute & Preventative)?
Acute attack: effective pain relief, triptans
Preventative (at least 1/week): Pizotifen, Propranolol, Amitryptyline, Topiramate, Valproate
How is TTH managed?
Aim at reassurance: no sinister cause
Attention to underlying chronic physical, psychological or emotional problems
Acute attacks: simple analgesia
Prevention: Amitryptiline
Discourage analgesics in chronic TTH
What is the difference between a seizure/fit, syncope and convulsion and an epileptic seizure (all paroxysmal events)?
Seizure/ Fit: Any sudden attack from whatever cause
Syncope: Faint (a neuro-cardiogenic mechanism)
Convulsion: Seizure where there is prominent motor activity
Epileptic seizure: an electrical phenomenon
Seizures can have different mechanisms
Many seizures are not epileptic in nature
What is an epileptic seizure and what does it depend on?
Epileptic seizure=An abnormal excessive hyper synchronous discharge from a group of (cortical) neurons
It may have clinical manifestations
Paroxysmal change in motor, sensory or cognitive function
Depends on seizure’s location, degree of anatomical spread over cortex, duration
What is epilepsy?
Epilepsy: A tendency to recurrent, unprovoked (spontaneous) epileptic seizures
A question that must be answered clinically, with recourse to EEG only for supportive evidence
Is a seizure always epilepsy?
NOOOOO
A seizure is not necessarily epileptic
Consequences of misdiagnosis of epilepsy can be serious
What are some examples of non epileptic seizures and other mimics in children?
Acute symptomatic seizures: due to acute insults eg. Hypoxia-ischaemia, hypoglycemia, infection, trauma
Reflex anoxic seizure: common in toddlers (vagal overstimulation-provoked/triggered)
Syncope
Parasomnias eg. night terrors
Behavioural stereotypies (repetitive movements)
Psychogenic non-epileptic seizures (PNES)
What is a febrile convulsion?
An seizure occurring in infancy/ childhood, usually between 3 months and 5 years of age, associated with fever but without evidence of intracranial infection or defined cause for the seizure
Commonest cause of ‘acute symptomatic seizure’ in childhood
What are the seizure types (can be challenging to distinguish between)?
Jerk/ shake: clonic, myoclonic, spasms
Stiff: usually a tonic seizure
Fall: Atonic/ tonic/ myoclonic
Vacant attack: absence, focal absence seizure
What is the mechanism of an epileptic fit?
Chemically triggered by chemical imbalance:
- Decreased inhibition (gama-amino-butyric acid, GABA)
- Excessive excitation (glutamate and aspartate)
- Excessive influx of Na and Ca ions
Chemical stimulation produces an electrical current
Summation of a multitude of electrical potentials results in depolarization of many neurons which can lead to seizures, can be recorded from surface electrodes (Electroencephalogram (EEG))
What are the main two types of epileptic seizures?
Generalised seizure (neurons recruited from both halves of the brain)
Partial/focal seizure (restricted to one hemisphere or part of one hemisphere)
What is the difference between childhood vs adult onset epilepsies?
Majority are idiopathic in origin (both Focal & Generalised)
Majority of epilepsies are generalised
Seizures can be subtle (absences, myoclonus, drop attacks)
Diagnosis can be challenging because:
- Non-epileptic paroxysmal disorders are more common in children
- Difficulty in explaining (Children are not young adults)
- Difficulty in interpretation (witness)
- Difficulty in interpretation and synthesising information(physician)
What is the stepwise approach to a diagnosis of epilepsy?
Is the paroxysmal event epileptic in nature?
Is it epilepsy?
What seizure types are occurring?
What is the epilepsy syndrome?
What is the etiology?
What are the social and educational effects on the child?
How is an EEG valuable in epilepsy and how is it not?
An interictal EEG has limited value in deciding when the individual has epilepsy
Sensitivity of first routine interictal EEG: 30- 60%
Problematic false positive rates: paroxysmal activity seen in 30%, frankly epileptiform activity in 5% of normal children
Useful in identifying seizure types, seizure syndrome and etiology
How is epilepsy diagnosed?
- History (before, during and after event)
- Video recording of event
- ECG in convulsive seizures (rule out long QT syndrome)
- Interictal/ ictal EEG
MRI Brain: to determine etiology eg. Brain malformations/ brain damage
Genetics: idiopathic epilepsies are mostly familial; also single gene disorders eg. Tuberous sclerosis
Metabolic tests: esp if associated with developmental delay/ regression
What is the management of epilepsies in children?
Anti-epileptic drugs (AED) should only be considered if diagnosis is clear even if this means delaying treatment
Role of AED is to control seizures, not cure the epilepsy
- Start with one AED: slow upward titration until side-effects manifest or drug is considered to be inefficient.
Age, gender, type of seizures and epilepsy should be considered in selecting AEDs
S/Es: CNS related can be detrimental; Drowsiness, effect on learning, cognition and behavioural
What drug treatment is available for epilepsy management?
Sodium Valproate (not in girls- recent MHRA advice) or Levetiracetam: first line for generalised epilepsies
Carbamazepine: first line for focal epilepsies
Several new AEDs with more tolerability and fewer side effects: Levatiracetam, Lamotrigine, Perampanel
Other therapies: steroids, immunoglobulins and ketogenic diet (mostly for drug-resistant epilepsies)
What are some more management strategies for epilepsy (usually for drug resistant epilepsies)?
VNS (palliative-lessen burden of seizures on every day life)
SURGERY (palliative or curative-localise origin & may facilitate a resection)
Assessing a child with an unusual head, why is this important?
Accurate measurements & interpretation as part of a childhood physical exam
Head size problems=Macrocephaly & microcephaly
Head shape problems-What not to miss
Refer early for specialist opinion
In what order do the fontanelles close?
At birth, the bones of the infant skull are not fused together
Posterior fontanelle usually closes 2-3 months after birth
Followed by gradual fusion of the sutures
Anterior fontanelle usually closes between 1-3 years of age (average=18 months)
What measurements should be done in terms of head circumference and in who should they be done?
Occipitofrontal circumference
As routine: Between birth- 3 years
In any child with neurological symptoms or developmental complaints
Measure and plot parental head sizes
Too big, too small or odd shape?
Sutures & Fontanelles?
Look at the facial features- any asymetry?
What is microcephaly and what does it usually indicate?
Definition: OFC <2 SD: mild
OFC <3 SD: moderate/ severe
Microcephaly usually indicates small brain: ‘micranencephaly’
Prenatal or postnatal onset: is it crossing centiles downwards?
Timing of onset may be a clue
Multiple causes: antenatal, postnatal, genetic and environmental
What is MACROcephaly and what should be considered?
Definition: OFC > 2SD
Is it crossing centiles upwards?- indicates that either the underlying brain or the underlying CSF is expanding in a way it shouldn’t
Sutures?-separation
Fontanelles?-very large
Familial?
Hydrocephalus?
Large brain?
Development normal?
Other physical abnormalities – facial features, hepatosplenomegaly, bony deformities etc
Head shape problems usually in first year of life: what should be asked and what are the types of head shape problems to be aware of?
Timing of onset?
Is it getting better or worse?
Plagiocephaly ‘flat-head’
Brachycephaly ‘short head or flat at back’
Scaphocephaly ‘boat shaped skull’
Craniosynostosis (premature fusion of the cranial sutures)
What is one of the commonest head shape problems
Deformational plagiocephaly
- Due to position child is in
- Parallelogram shape skull
What is craniosynostosis?
Premature fusion of one or more sutures
Depending on which suture closed too early you may get some classical characteristic shapes which may indicate the type of synostosis is
How is craniosynostosis usually assessed?
Either cranial CT scans or occasionally skull x-rays
What would make you suspect a NM disorder?
- Baby ‘floppy’ from birth
- Slips from hands
- Paucity of limb movements
- Alert, but less motor activity
- Delayed motor milestones
- Able to walk but frequent falls
What does the Gowers sign indicate?
Weakness around the pelvic girdle and lower limb muscles in particular
Prominent clinical sign which may indicate an underlying muscle condition (e.g. Muscular dystrophy)
What is the most common muscular dystrophy occurring in childhood?
Duchenne muscular dystrophy
1/3500 male infants
What gene is affected in DMD and what are the signs of this condition?
Xp21, dystrophin gene, 1/3500 male infants
Delayed gross motor skills
Symmetrical proximal weakness
- Waddling gait, calf hypertrophy
- Gower’s sign positive
Elevated Creatinine Kinase levels = >1000 in DMD
Cardiomyopathy
Respiratory involvement in teens
Pes cavus (high arch feet) is a classic sign seen in what?
Some types of hereditary motor sensory neuropathies (typified by the charcot marie tooth disease)
What is the anatomical approach to neuromuscular conditions to determine where is the sight of the lesion and what is the lesion?
Muscle: muscular dystrophies, myopathies- congenital and inflammatory, myotonic syndromes
Neuromuscular junction: myasthenic syndromes
Nerve: Hereditary or acquired neuropathies
Anterior Horn Cell: Spinal muscular atrophy
