Neurological disease in a child Flashcards
Cerebral/intraventricular haemorrhage, CNS tumours, epilepsy, hydrocephalus, infantile spasm, migraine, tic disorder, Becker/Duchenne/Myotonic muscular dystrophy, neurocutaneous syndromes
List 3 causes of neonatal hypotonia.
- Sepsis
- Wednig-Hoffman disease (spinal muscular atrophy type 1)
- Hypothyroidism
- Prader-Willi
What are 2 maternal causes of neonatal hypotonia?
- Maternal drugs e.g. benzodiazepines
- Maternal myaesthenia gravis
Define muscular dystrophy.
Progressive, generalised disease of muscle, most often caused by defective or specifically absent glycoproteins (e.g., dystrophin) in the muscle membrane.
All muscular dystrophies are characterised by ongoing degeneration and regeneration of muscle fibres
What is the most common and rapidly progressive muscular dystrophy?
Duchenne muscular dystrophy
What is the aetiology of Duchenne/Becker muscular dystrophy?
Duchenne/Becker muscular dystrophies are caused by a mutation of the dystrophin gene located on the small arm (p) of the X chromosome at the Xp21 position.
What is seen on muscle biopsy in Duchenne and Becker muscular dystrophy?
Duchenne = absent dystrophin on muscle biopsy
Becker = diminished quantity or quality of dystrophin in muscle biopsy specimens
How common is DMD, BDM and myotonic muscular dystrophy?
DMD - 1 in 3000 males, uncommon in females
BMD - 1 in 25,000
Myotonic dystrophy - more common in northern Italy where prevalence is 1 in 30,000
What is the size of the dystrophin gene? Where is dystrophin present?
Dystrophin gene is largest gene in human genome
Dystrophin is present everywhere but greatest in skeletal muscle so they are most affected by its loss
What is the aetiology of myotonic dystrophy?
Defective gene on chr19 = triplet repeat sequence of DNA is abnormally expanded many times.
A second form also exists with gene defect on chromosome 3q.
Clinical severity increases with increasing nucleotide triplet repeats.
What is the impact of absence of dystrophin in cells?
Causes ongoing cell membrane depolarisation (due to calcium entering the cell) —> ongoing degeneration and regeneration of muscle fibres —> degeneration is faster —> necrosis of muscle fibres
Apart from skeletal muscle, what other systems are affected by DMD/BMD?
Brain - learning difficulties and ASD seen in DMD
Cardiac - cardiomyopathy
Intestinal - longer transit time
What are the signs and symptoms of muscular dystrophy?
- Hypotonia at birth
- Toddler with delayed motor milestones
- Frequent falls
- Attention deficit and hyperactive
- Calf hypertrophy - due to regeneration of muscle fibres
- Proximal hip gurdle muscle weakness
- Gower’s sign
- Lumbar lordosis
- Heel cord contractures
- Toe walking - to keep centre of gravity behind hips and in front of knees
- Wide-based, waddling unstable gait
What is a characteristic finding in muscular dystrophy bloods?
Marked CK elevation (x50-100 of normal). However, usually only reaches this level at 1yr and peaks at 5yrs.
What are the reflexes in muscular dystrophy like?
Diminished reflexes in all muscle groups
Apart from CK, what other investigations can be performed for DMD?
DNA analysis - Xp21 deletion in 2 thirds of cases
Gene sequencing - done if no deletion
EMG - distinguish between neuropathic and myopathic causes
Muscle biopsy - histochem /immunochem /immunoblot testig done
What is the difference in presentation between BMD and DMD? What is the prognosis of BMD?
BMD usually later age of onset and clinical involvement is milder; at least 3% normal dystrophin on biopsy.
Age of onset ~11 years
Loss of ambulation in late 20s
Life expectancy to middle or old age
May get arrhythmias, congestive HF
When is the age of onset of DMD? What is the prognosis?
- Progressive proximal muscle weakness from 5 years
- Most no longer ambulant by 10-14 years
- Life expectancy to late 20s (due to respiratory failure/cardiomyopathies)
What is Gower’s sign?
Turn pronne and climb up own body to rise
What is the management of DMD?
Physiotherapy - prevents contractures,
Surgery - tendoachilles lengthening and scoliosis surgery
CPAP for nocturnal hypoxia - from weakness of intercostal muscles, causing daytime headache, irritability and loss of appetite
Corticosteroids if ambulant - preserve mobility and prevent scoliosis by unknown mechanism
Research into new drugs e.g. exon skipping drugs, Ataluren for nonsense mutation DMD is now available.
Define dystrophia myotonica.
Delayed relaxation after sustained muscle contraction. Can be identified clinically and by EMG.
What is the age of onsent of dystrophia myotonica? What does it affect?
Features developing at around 20-30 years old. It affects skeletal, cardiac and smooth muscle
What are the types of myotonic dystrophy?
What is the aetiology of dyrstrophia myotonica? How does inheritance change with generations?
Relatively common and inherited
Caused by nucleotide triplet repeat expansion, CTG in the DMPK gene
There can be anticipation through generations, especially when materanally tarnsmitted.
What are the signs/symptoms of dystrophia myotonica?
Newborns: hypotonia, feeding and respiratory difficulties, thin ribs, talipes at birth, oligohydramnios, reduced fetal movemnets at pregnancy.
Later:
- myopathic facial features (‘haggard’ appearance)
- dysphagia
- learning difficulties
- myotonia (prolonges muscle tensing) e.g. slow release of handshake, difficulty releasing tightly clasped fist
- initially distal weakness of arms and legs
- dysarthria
- males - baldness, testicular atrophy
- cataracts, bilateral ptosis
- T2DM
- cardiac dysrrhythmias
Define anticipation.
When myotonic dystrophy is passed from one generation to the next, it generally begins earlier in life and signs and symptoms become more severe.
What is the prognosis of myotonic dystrophy?
- Type 2 have a better prognosis than type 1
- Depends on extent of cardiac involvement as death is usually due to conduction defects.
- Walking into 60s
- Normal life expectancy in most
What is the management of dystrophia myotonica?
No treatment, symptomatic only
- Physiotherapy - muscle strength and endurance and to control musculoskeletal pain. Canes, braces, walkers, and scooters can help.
- Pain management
- Insertion of a pacemaker, medications, and regular monitoring of cardiac function.
- Cataracts - surgically removed.
- Testosterone replacement therapy may be used to treat infertility in males.
Define neurocutaneous syndrome and list 3 examples.
Conditions affecting the skin and nervous system. These both have a common ectodermal origin and embryological disruption can cause these syndromes.
- Neurofibromatosis
- Tuberous sclerosis
- Struge-Weber syndrome
How common is neurofibromatosis? What are the causes?
NF-1: affects 1 in 3000, it is autosomal dominant, highly penetrant condition, caused by mutation in the NF-1 gene (arises in 50% as a de novo mutation)
NF-2: less common than NF-1, it is autosomal dominant caused by mutation in the NF2 gene, 50% due to de novo mutations.
What is the criteria for diagnosis of NF-1?
2 or more of:
- 6+ café-au-lait spots >5 mm in size before puberty, or >15 mm after puberty
- >1 neurofibroma
- axillary freckling
- optic glioma which may cause visual impairment
- 1 Lisch nodule
- bony lesions from sphenoid dysplasia, which can cause eye protrusion
- a first-degree relative with NF-1.
What is a Lisch nodule?
a hamartoma of the iris seen on slit-lamp examination
When do cutaneous features of NF-1 usually appear?
More prominent after puberty but there is a spectrum from mild to severe symptoms
What are the common complications of neurofibromatosis type 1?
Neurofibromata - can occur in any peripheral nerve, including cranial nerves causing neurological signs e.g. visual or auditory impairment if there is compression of CN II or VIII
Macroencephaly
Epilepsy
What features are common to NF-1 and NF-2?
NB: most people only have cutaneous stigmata.
- Endocronological disorders e.g. multiple endocrine neoplasia syndromes.
- Phaeochromocytomas
- Pulmonary hypertension
- RAS with hypertension
- Benign tumours may undergo sarcomatous change
What features are common in NF-2? What is a common complication?
- multiple inherited shwannomas
- meningiomas
- ependymomas
Bilateral acousitic neuromata are common causing deafness and cerebellopontine angle syndrome with facial (CNVII) nerve paresis and cerebellar ataxia
What is the cause of tuberous sclerosis? How common is it?
1 in 9000 affected
Autosomal dominant, variable penetrance, up to 70% of mutations arising de novo. Mutations in the TSC1 or TSC2 genes.
What are the cutaneous features of tuberous sclerosis?
- Depigmented “ash leaf” shaped patches or amelanocytic naevi which fluoresce under UV light (Wood’s light)
- Rough patches of skin (shagreen patches) esp over lumbar spine
- Angiofibromata (“adenoma sebaceum”) in a butterfly distribution over the bridge of the nose and cheeks, unusual before age of 3 years
What is shown?
Facial angiofibromas in tuberous sclerosis
What are the neurological features of tuberous sclerosis?
Neurological features are seen in 50%, including:
- infantile spasms and developmental delay
- epilepsy – often focal
- intellectual disability, often with autism.
Children with early onset intractable epilepsy have severe learning difficulties and often have autistic features when older.
What are the other features of tuberous sclerosis (non cuteneous/neurological)?
- fibromata beneath the nails (subungual fibromata)
- dense white areas on the retina (phakomata) from local degeneration
- rhabdomyomata of the heart which are identifiable in the early weeks on echocardiography but usually resolve in infancy
- angiomyolipomas and polycystic kidneys
- cysts in the lungs
What is found on brain imaging in tuberous sclerosis and what is a complication of this?
In the brain, even if asymptomatic, there are subependymal nodules and cortical tubers (look calcified on CT, present from >2years ).
May enlarge over time and form subependymal giant cell astrocytomas which sometimes block the flow of CSF –> headache, vomiting, and hydrocephalus.
What is the cause of Sturge-Weber syndrome?
Sporadic disorder
Which nerve is always involved in Sturge-Weber syndrome?
Ophthalmic division of the trigeminal nerve
What eye probelm are neonates with SWS at risk of?
50% may develop glaucoma
What are the features of SWS?
- Haemangiomatous facial lesion (port wine stain) in the distribution of CNV
- Intracranial lesion ipsilaterally (ipsilateral leptomeningeal angioma)
If severe:
- Epilepsy
- Itellectual disability
- Contralateral hemiplegia
What is seen on brain imaging in SWS?
“rail-road track” calcification of the gyri on skull XR but usually an MRI is done
What is a possible management of intractable epilepsy in children with SWS?
Hemispherotomy in early infancy
How can port wine stains be managed?
Laser treatment can be used to lighten or remove them
What is the prognosis with SWS if a child only has mild symptoms at <5 years?
Good prognosis; although there may still be seizures and learning difficulties.
Define hydrocephalus.
An accumulation of cerebrospinal fluid in the brain.
What are the main 2 types based on aetiology of hydrocephalus?
- congenital hydrocephalus – hydrocephalus that’s present at birth, associated with cerebral malformations
- acquired hydrocephalus – hydrocephalus that develops after birth, (obstruction to flow of CSF causing dilatation of the ventricular system proximal to the side of obstruction)
What are the two types of hydrocephalus based on site of obstruction?
Non-communicating - obstruction in the ventricular system of the aqueduct
Communicating - obstruction at the arachnoid villi which is the site of absorption of CSF
What are the clinical features of hydrocephalus in a baby and older child?
Infants - separation of the skull sutures, large head circumference or showing excessive growth, bulging anterior fontanelle, prominent scalp veins, “sun setting” of the eyes
Older children - symptoms of raised ICP
How is hydrocephalus diagnosed?
Antenatally - ultrasound
If suspected in infancy - cranial ultrasound or CT/MRI brain, head circumference monitoring on centile chart.
What are the causes of communicating and non-communicating hydrocephalus?
Non-communicating = obstruction in the ventricular system
- Congenital malformation:
- aqueduct stenosis
- atresia of the outflow foramina of the fourth ventricle
- Chiari malformation
- Posterior fossa neoplasm or vascular malformation
- Intraventricular haemorrhage in preterm infant
Communicating = failure to reabsorb CSF
- Subarachnoid haemorrhage
- Meningitis e.g. pneumococcal, tuberculosis
What is the management of hydrocephalus?
Symptomatic relied of raised ICP and minimising risk of neurological damage
- insertion of venticuloperitoneal shunt
- endoscoping creating of ventriculostomy
What are the complications of venticuloperitoneal shunts?
Shunts can malfunction due to blockage or infection (usually with coagulase-negative staphylococci).
They then need replacing or revising.
Overdrainage of fluid can cause low-pressure headaches but the insertion of programmable valves can help avoid this.
Which organism is most commonly implicated in ventriculoperitoneal shunt infections?
Coagulase negative staphylococci
Define tics.
Quick, sudden, coordinated movements which are apparently purposeful and recur in the same part of a child’s body.
Are tics involuntary?
Partially, they can be supressed to an extent
How common are tics? Who is most commonly affected? What is the average age of onset/worst symptoms?
1 in 10 children develop a tic at some stage
Boys most commonly affected
Average onset at age 8yrs, peak symptoms as age 11yrs and symptoms improve thereafter
What are some common tics? When do they usually occur? What makes them better/worse?
Blinking, frowning, head-flicking, sniffing, throat clearing, grunting are common.
Most likely to occur when inactive (watching TV or long car journey)
Better: disappear when concentrating
Worse: when anxious, but are not themselves a reaction
Name a risk factor for tics.
Family history
What is the prognosis of tic disorder?
- Most do not need treatment
- Symptoms can fluctuate in severity
- Transient tic disorder - clear up over a few months but may recur
- Uncommonly, there are children who are hardly every free of tics
What is coprolalia?
Swearing as a tic, very uncommon
What is considered as chronic tic disorder?
If the tics continue for over 12 months, but they may still resolve in adulthood
What is Gilles de la Tourette syndrome?
Tourette’s - multiple motor AND vocal tics such as grunting, coughing, humming, squeaking. Tends to be persistent in the medium term.
What is the management of persistent tics e.g. Tourette’s?
CBT and habit reveral techniques - 1st line
More serious cases may require medication like clonidine or risperidone - 2nd line
What is the MOA of clonidine and rosperidone?
clonidine - adrenergic alpha2 antagonist in the posterior medulla and hypothalamus –> reduces sympathetic outflow from CNS
rosperidone - mainly 5HT (seritonin) receptor antagonist but also some D2 (dopamine) receptor antagonism –>
What are the two most common brain tumour types in children?
Astrocytoma (~40% of all brain tumours in children) - varies from benign to malignant (glioblastoma multiforme)
Medulloblastoma (~20%) - arise in midline of the posterior fossa. May seed through CNS via the CSF and up to 20% have spinal metastases at diagnosis
Are most brain tumours primary or secondary in children? Where are most located?
Almost always primary (rather than metastatic as in adults)
60% are infratentorial
What is the most common solid tumour in children and the leading cause of death?
Brain tumours are the most common solid tumour in childhood and the leading cause of death in children
What are the other types of brain tumour in children?
Ependymoma (8%) - most common in posterior fossa, behaves like a medulloblastoma
Brainstem glioma (6%) - malignant tumours associated with very poor prognosis
Craniopharyngioma (4%) - developmental tumour arising from squamous remnant of Rathke pouch. Not truly malignant but locally invasive and grows slowly in the suprasellar region.
Atypical teratoid/rhabdoid tumour - rare type of aggressive tumour that most commonly occurs in young children
Which childhood brain tumour is…
- developmental tumour arising from squamous remnant of Rathke pouch.
- most common in posterior fossa, behaves like a medulloblastoma
- rare type of aggressive tumour that most commonly occurs in young children
- malignant tumours associated with very poor prognosis
- not truly malignant but grows slowly in the suprasellar region
- Craniopharyngioma (4%)
- Ependymoma (8%)
- Atypical teratoid/rhabdoid tumour
- Brainstem glioma (6%)
- Craniopharyngioma (4%)
What pathophysiology should you suspect in headaches and behavioural change?
Raised ICP
What are the clinical features of brain tumours?
All ages:
- Abnormal eye movements
- Abnormal head position - wry neck, head tilt or perisstent stiff neck
- Persistent/recurring vomiting
- Problems with balance, coordination or walking
- Behavioural change
- Seizures
Child/adolescent
- Headache
- Blurred/double vision
- Lethargy, deteriorating school performance, delayed or arrested puberty, slow growth
Infants
- Progressive increase in head circumference, separation of sutures, bulging fontanelle
- Lethargy, developmental delay/regression
Where are childhood tumours located in the brain and spinal cord?
What are the clinical features specific to tumours in:
- Supratentorial - cortex
- Midline
- Cerebellar and IVth ventricle
- Brainstem
- Supratentorial - cortex - seizures, hemiplegia, focal neurological signs
- Midline - visual field loss (bitemporal hemianopia), pituitary failure (growth failure, DI, weight gain)
- Cerebellar and IVth ventricle - truncal ataxia, coordination difficulties, abnormal eye movements
- Brainstem - cranial nerve defects, pyramidal tract signs, cerebellar signs (ataxia), no raised ICP
What is the most likely location of the tumour?
- 4yearold. Refuses to walk, unable to climb stairs, squint, facial asymmetry and drooling.
- 10yearold complaining of headaches, vomiting, poor growth, struggling to see the board at school.
- 14yearold. Aggressive behaviour at school, headaches, seizure
- 3yearold vomiting in the mornings, unsteady on his feet, newonset convergent squint.
- brainstem glioma (picture e)
- craniopharyngioma (picture c)
- astrocytoma - glioblastoma multiforme (picture b)
- medulloblastoma - (picture d)
What investigation is required in a child with persistent back pain?
MRI - other symptoms such as peripheral weakness or arms or legs, bladder/bowel dysfunction can be present.
What investigations are required for suspected brain tumours?
MRI - best for characterisation of the tumour. Can also use magentic resonance spectroscopy to examine its biological activity.
Lumbar puncture - some tumours can metastasise within the CSF and so LP is required for complete staging. DO NOT PERFORM IF SUSPECTED RAISED ICP
What is the management of brain tumours?
- Surgery - for treating hydrocephalus, for tissue diagnosis, maximum resection
- +/- chemotherapy/radiotherapy - depecing on tumour type and age of patient
When might biopsy not be suitable in brain tumours?
anatomical position such as being in the brainstem or optic pathway e.g. in gliomas biopsy is too hazardous
What are the complications of brain tumours after treatment?
- Neurological disability
- Growth problems
- Endocrine disorders
- Neuropsychological and educational problems
What is the prognosis with brain tumours in children?
Relatively poor prognosis
- glioblastoma multiforme - <30% survival
- brainstem glioma - palliative radiotherapy, <10% survival
- craniopharyngioma - survival but long-term visual impairments, pituitary insufficiency
- medulloblastoma - improving survival but 5-year survival about 50%
- ependymoma - behaves like medulloblastoma
- astrocytomas - usually cystic and slow growing, with good prognosis after surgery
What % of VLBW infants have brain haemorrhages? How are they diagnosed?
20% these are recognised on cranial ultrasound - most intraventricular haemorrhages occur in the first 72 hours of life
Where are most brain haemorrhages located in VLBW neonates?
- In the germinal matrix above the caudate nucelus, which contains a fragile network of blood vessels
- May extend into the ventricles
- If it invovles the parenchyma of the brain then may cause hemiplegia
What are the risk factors for intraventricular haemorrhage perinatally?
- Perinatal asphyxia in RDS
- Pneumothorax
Reduced risk with glucocorticoids prior to preterm delivery –> reduced RDH –> reduced IVH
What are the complications associated with IVH? How can they be managed?
Hydrocephalus - from impaired reabsorption of CSF–> increasing pressure and dilatation. Initially symptomatic relief with removal of ventriculoperitoneal shunt may be required
Cerebral palsy - from progressive-post heamorrhagic ventricular dilatation , parenchymal infarction or periventricular white matter injury in the absense of ischaemia/inflammation (difficult to detect by US)
What is periventricular leukomalacia?
Bilateral multiple cysts - 80-90% risk of spastic diplegia
What findings on US in IVH point towards poor prognosis? Are clinical findings on US always indicative of prognosis?
Echodense area/’flare’ - may resolve and not have complications
Cystic lesions - become visible 2-4 weeks later and indicate definite loss of white matter
Bilateral multiple cysts - periventricular leukomalacia (PVL) = 80-90% risk of spastic diplegia
No abnormal clinical signs - 30% of premature infants born <32 weeks with no abnormal US findings go on to have cerebral palsy
What are the three types of intracranial haemorrhage?
- Extradural
- Subdural
- Subarachnoid
Extradural haematoma
- What is the most common cause in children?
- What is the clinical presentation?
- How is diagnosis confirmed?
- What is the management?
- Cause - head trauma causes tearing of the middle meningeal artery which passes through foramen spinosum of sphenoid bone –> arterial/venous bleeding into extradural space.
-
Clinical presentation -
- lucid interval until GCS deteriorates
- seizures with increasing size if haematoma
- focal neurological signs: dilatation of ipsilateral pupil, paresis of contralateral limgs, false lovalising unilateral or bilateral VIth nerve palsy
- young children: anaemia/shock
- Investigations- CT
- Management - correct hypovolaemia, urgent evacuation of haematoma + arrest bleeding
Subdural haematoma:
- What are the most common causes?
- What associated signs may be present?
-
Cause: tearing of bridging veins in the subdural space,
- commonly found as a result of shaking of NAI
- or following fall from considerable height
- Associations: May be associated with retinal haemorrhages (also from shaking) or with brain shrinkage from atrophy or rarely overdrainage of hydrocephalus
Subarachnoid haemorrhage
- What are the most common causes?
- What are the clinical features?
- What investigations are diagnostic?
- What is the management?
- Cause - More common in adults but may be associated with aneurysm or arteriovenous malformations
-
Clinical features -
- thunderclap headache
- vomiting
- confusion/lowered GCS
-
Investigations
- CT scan shows blood in CSF
- LP may be required if not
- MR angiography for AVMs
- Management - neurosurgery with interventional radiology
