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
Define hydrocephalus.
An accumulation of cerebrospinal fluid in the brain.
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
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.
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
Where are childhood tumours located in the brain and spinal cord?
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)
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
