Neuro Flashcards
Neural Tube Defects - background
- Key points
a. One of the most common congenital abnormalities
b. Abnormal closure of the neural tube – which forms the spinal cord, vertebrae and skin coverings
c. Spinal dysraphism = spina bifida - Epidemiology
a. 1/10,000
e. Incidence of new cases – 5 new cases/year at RCH
f. Main reason for reduction is antenatal diagnosis and termination; i. Secondarily reduced due to folate - Pathogenesis
a. Conception to day 18 = formation of germ layers
i. Ectoderm to form neural plate
b. Day 19 to day 28 = neural tube folds
i. Begins in cervical region and closure extends both rostrally (D24) and caudally (28)
ii. Failure to close by D28 = NTD - Etiology + risk factors
a. Folate deficiency
i. Most isolated NTDs are caused by folate deficiency
iii. Folic acid antagonists = valproic acid, carbamazepine, MTX
b. Genetic factors
i. High concordance between monozygotic twins
ii. Recur within families
c. Syndromes = Meckel-Gruber, Roberts, Jarcho-Levin, HARD, T13, T18
f. Diabetes
g. Obesity
a. Folate supplementation reduces recurrence by 72%
Neural Tube Defects - classification
a. Open spinal dysraphism
i. Characterised by cleft in the vertebral column with corresponding defect in the skin
ii. Exposed meninges and spinal cord
iii. Comprise 80% of all NTDs
iv. Associated with Chiari malformations and ventriculomegaly
v. Includes
1. Spinal
a. Myelomeningocele (contains neural tissue)
b. Meningocele (no neural tissue)
2. Cranial
a. Encephalocele (brain and meninges)
b. Anencephaly (absence of a major portion of the brain, skull, and scalp)
b. Closed spinal dysraphism = spina bifida occulta
i. Characterised by cleft in vertebral column
ii. No epithelial defect – may have tuft of hair, dimple, birthmark
iii. Not usually associated with cranial malformations
iv. Includes
1. Lipomyelomeningocele (an abnormal growth of fat attaches to the spinal cord and its membranes)
2. Lipomeningocele
92% occur at/below L3
Neural Tube Defects - investigation
- Investigations + diagnosis
a. AFP = Failure of closure -> increased AFP excreted in amniotic fluid (open more so than closed)
b. Prenatal USS 18-20 weeks
i. Detailed fetal anatomy
ii. Feto-maternal obstetric outpatient for discussions and counselling
iii. Termination at 20-22 weeks should the parents choose
Closed Spinal Dysraphism - general
- Key points
a. Characterised by failure of fusion of vertebral bodies – abnormal fusion of the posterior vertebral arches
b. Results in exposed neural tissue
c. Skin overlying defect is intact - Clinical manifestations
a. Cutaneous
i. Patch of hyperkeratosis
ii. Patch of hypertrichosis
iii. Patch of hyperpigmentation
iv. Patch of epidermal atrophy
v. Subcutaneous mass (lipoma or neurofibroma)
vi. Capillary haemangioma or cutaneous angioma
vii. Dorsal dermal sinus
viii. Sacrococcygeal pit
ix. Sacrococcygeal dimple
x. Caudal cutaneous appendage
xi. Isolated deviation of the intergluteal fold
b. Neurological
i. Neurological abnormalities in legs
1. Motor weakness
2. Sensory loss
3. Reflex changes
4. Abnormal plantar response
ii. Tethered cord syndrome
1. Stretch-induced dysfunction of the caudal spinal cord and conus
2. Presentation of several forms of closed spinal dysraphism
3. Results in back pain, bladder dysfunction, leg weakness, calf muscle atrophy, reduced tendon reflexes, loss of sensation, scoliosis + foot deformities
c. Urological
i. Neurogenic bladder dysfunction
ii. Urological abnormalities
d. Musculoskeletal
i. Scoliosis
ii. Kyphosis
iii. Lordosis
iv. Leg length discrepancy
v. Foot deformities
Complications Spina Bifida - neuro (hydrocephalus, tethered cord syndrome)
a. Hydrocephalus
i. 3/4 develop significant hydrocephalus requiring treatment
ii. By 1 month of age 80% develop hydrocephalus
iii. Levels 2 and 3 (thoracic + upper lumber) more likely to get hydrocephalus
iv. Usually present by 1 month of age
1. Shunts are usually inserted in first 2/12 of life
2. Rarely develops after 6 months
Intellectual function/disability highly correlates with hydrocephalus
b. Tethered cord
i. Traction, damage to neural tissue
ii. Common at birth
iii. Highest recurrence at peak longitudinal growth (puberty) but can occur at any time
iv. Monitor = serial MRI
v. Symptoms and signs- changes in:
1. Bladder/bowel function
2. Foot position
3. Back or lower limb pain
Complications Spina Bifida - urological (neuropathic bladder)
Neuropathic bladder
a. Key points
i. Urinary tract innervated by sacral segment
ii. All children expected to have neuropathic bladder – 25% continent, tend to be those with little or no sensory loss
iii. Renal failure was historically the major cause of death in those with Spina Bifida
iv. Intermediate bladder most common
b. Monitoring
i. Ultrasound – usually done every 6/12
ii. Other (urodynamics, MCS, creatinine)
c. Goals
i. Preserve renal function = ensure emptying + prevent infection
ii. Achieve continence
- Medical: intermittent catheterisation, anticholinergics, treat infections
- Surgical: botulinum toxin, sphincterotomy, vesicostomy, Mitrofanoff
NOTE 35% develop IgE mediated latex allergy
Spinda Bifida Complications - GIT (neuropathic bowel)
a. Key points
i. Usually in those with S2/S3 affected
ii. 25% of adults with spina bifida are bowel continent
iii. Most who are incontinent have poor sensation and either
1. Increased bowl outlet resistance constipation and overflow diarrhoea
2. Decreased bowel outlet resistance frequent stools throughout the day
b. Management
i. Diet, fluids – recommend low fibre diet to reduce volume of stool
ii. Regular sit, cough, push on toilet
iii. Laxatives – start laxatives very early (<2 years)
iv. Enemas, washouts
v. Anal plugs – previously used for swimming
vi. Biofeedback
vii. Malone procedure – antegrade washouts; usually appendix to skin
viii. Peristeen irrigation system – rectal catheter used to flush bowel
ix. (Exclude other causes of diarrhoea)
c. Continence nurses
i. Advise – management of bladder and bowels
ii. Training (CIC, washouts) – parents, carers, aides and patients
iii. Applications for funding
iv. Sourcing equipment (catheters, pads, nappies, specialised underwear)
v. Supplied by NDIS
Spina Bifida Complications - MSK
a. Based on age
i. Neonatal priorities
1. DDH
2. Clubfoot
ii. Childhood
1. Independence, mobility, positioning
4. AFO (ankle foot orthosis) most common aid
iii. Teenager
1. Monitor scoliosis
b. Mobility aids
i. The higher the lesion the less the chance of independent walking BUT the anatomical level does not always predict function accurately
c. Physiotherapy
1. If a sudden change may indicate tethering
d. Orthopaedic surgery
i. Common reason for admission
ii. Abnormal pressure on joints
iii. Scoliosis
e. Sensation
i. Sensory loss below level of lesion – patchy or dense
ii. High risk of pressure areas burns
1. Slow healing (poor blood supply)
2. Historically, common cause of death
3. Big cause of morbidity in adults
iii. Occupational therapists
Spina Bifida Complications - transition of care
a. Kidney, bladder and bowel most important long term
b. Less commonly have any further neurosurgical or orthopaedic interventions later in life
c. RCH/RMH transition program
d. Consider private insurance for urologist unless attends RMH
Lissencephaly - general
“Smooth brain”
- Key points
a. Rare disorder
b. Characterised by absence of cerebral convolutions + poorly formed sylvian fissure
c. Appearance of 3-4 month fetal brain - Clinical manifestations
a. FTT
b. Microcephaly
c. Developmental delay
d. Seizure disorder - Syndromic forms
a. Miller-Dieker syndrome
i. Present in 15% of cases
ii. Characteristic facies = prominent forehead, bitemporal hollowing, anteverted nostrils, prominent upper limb, micrognathia
iii. Genetics - 70% have visible or submicroscopic deletion on chromosome 17p13.3
- Deletion of LIS-1 gene
b. Walker-Warburg variant
Schizencephaly - general
Radiopedia: “generally speaking, schizencephaly is reserved for clefts lined by grey matter (polymicrogyria) thought to represent a true malformation, whereas porencephaly implies an encephaloclastic event (e.g. ischemia)”
Abnormal slits or clefts form in the cerebral hemispheres of the brain
- Key points
a. Unilateral or bilateral clefts within the cerebral hemispheres due to abnormal morphogenesis
b. Cleft may be fused or unfused – if unilateral and large can be confused for porencephalic cyst
c. Borders of cleft surrounded by abnormal brain – microgyria
d. Genetic mutations may be involved with familial Schizencephaly - Clinical manifestations
a. Bilateral
i. Severe ID
ii. Seizures
iii. Microcephaly
iv. Spastic quadriparesis
b. Unilateral
i. Congenital hemiparesis
Polymicrogyrias - general
Polymicrogyria is a condition characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small.
- Polymicrogyria is characterised by an augmentation of small convolutions separated by shallowed enlarged sulci
- Commonly results in drug resistant epilepsy
Porencephaly - general
“Pore”
Radiopedia: “generally speaking, schizencephaly is reserved for clefts lined by grey matter (polymicrogyria) thought to represent a true malformation, whereas porencephaly implies an encephaloclastic event (e.g. ischemia)”
- Key points
a. Porencephaly = presence of cysts or cavities within the brain that result from developmental defects (schizencephaly) or acquired lesions, including infarcts.
ii. Tend to be unilateral, do not communicate, not associated with other CNS malformations
iii. Present with hemiparesis + focal seizures - Risk factors
a. Haemorrhagic venous infarctions
b. Thrombophilia
c. Perinatal alloimmune thrombocytopaenia
d. vWD
e. Maternal warfarin
f. Maternal cocaine
g. Congenital infections
h. Trauma
i. Maternal abdominal trauma - Clinical manifestations
a. ID
b. Spastic hemiparesis or quadriparesis
c. Optic atrophy
d. Seizures
Corpus Callosum Agenesis - general
- Key points
a. Heterogenous group of disorders
b. Severity ranges from severe ID to normal intelligence - Genetics
a. Absence of corpus callosum can be X linked or AD trait
b. Associated with chromosomal disorders – trisomy 8 and trisomy 18 - Pathogenesis
a. Corpus callosum develops from the commissural plate
b. Either a direct insult to the commissural plate or disruption of the genetic signaling that specifies and organizes this area during early embryogenesis causes agenesis of the corpus callosum - Clinical manifestations
a. Phenotype depends on accompanying abnormalities
i. Isolated phenomenon may be asymptomatic
ii. If associated with heterotopias, polymicrogyria and pachygyria it results in significant abnormalities - Aicardi syndrome
a. Key features
i. Agenesis of corpus callosum
ii. Distinctive Chorioretinal lacunae
iii. Infantile spasms
iv. Severe ID
b. Patients almost all female
c. Seizures evident during the first few months and are resistant to anticonvulsants
d. EEG = independent activity across hemispheres, hemihypsarrhythmia
Holoprosencephaly - general
- Key points
a. Developmental disorder of the brain – results from defective formation of the prosencephalon and inadequate forebrain structures
- prosencephalon becomes telencephalon (cerebral hemispheres) and diencephalon (optic cup/stalk, hypothalamus, thalamus, pituitary)
b. Associated features – facial abnormalities (cyclopia, synophthalmia, cebocephaly, single nostril, choanal atresia, solitary central incisor) - Aetiology
a. Genetic
b. Associated with maternal diabetes - Clinical manifestations
a. High mortality rate
b. Difficult to prognosticate – some cases less severe
Mobius Syndrome
- Characterise by bilateral facial weakness
- Often associated with bilateral CNVI palsy
- Results from hypoplasia/ agenesis of brainstem nuclei
- Usually present with facial weakness resulting in difficulty feeding
Duane Retraction Syndrome
- Congenital limitation of horizontal globe movement + globe retraction on attempted adduction
- Abnormal innervation by the oculomotor nerve of the lateral rectus muscle
Dandy-Walker Malformation
• Posterior fossa abnormalities including
o Cystic dilatation of the fourth ventricle
o Hypoplasia of the cerebellar vermis
o Hydrocephalus
o Enlarged posterior fossa
• Variable degrees of neurological impairment
• Unknown cause
Joubert Syndrome
• AR disorder – ciliopathy • Genetic heterogeneity • Associated with cerebellar vermis hypoplasia and pontomesencephalic molar tooth sign (depending on the interpeduncular fossa with thick and straight superior cerebellar peduncles) • Clinical manifestations o Hypotonia, ataxia (toddler) o Breathing abnormalities – episodic apnoea and hyperpnoea o Global developmental delay o Strabismus o Occulomotor ataxia • Associated features o Progressive retinal dysplasia – Leber congenital amaurosis o Coloboma o CHD o Microcystic kidney disease
Chiari Malformations - general
- Key points
a. Congenital malformation
b. Most common malformation of the posterior fossa and hindbrain
c. Herniation of the cerebellar tonsils through the foramen magnum +/- abnormality of bones with small posterior fossa
Types 1/2/3 - separate note
- Clinical manifestations (General)
b. Asymptomatic or symptomatic
c. If symptomatic – develop in late childhood
i. Headaches that worse with straining of maneuvers that increase ICP
ii. Symptoms of brainstem compression – diplopia, oropharyngeal dysfunction, spasticity, tinnitus, vertigo
iii. Obstructive hydrocephalus and/or syringomyelia can also occur - Investigations
a. Foetal USS may Dx if ventriculomegaly/myelomeningocele
b. MRI T1 and T2 of brain and spinal cord
c. CT to assess associated bony abnormalities - Treatment
a. Conservative = surveillance
b. Medical (supportive/manage complications)
c. Surgical
i. Repair of myelomeningocele
ii. Decompressive surgery if symptomatic
iii. Shunt if hydrocephalus
Chiari Malformations - types
a. Type I
i. Features
1. Cerebellar tonsils abnormally shaped
2. Displaced below level of foramen magnum
iii. Clinical manifestations
1. Insidious, present in adolescence (mean age 18yo)
2. Increased ICP
3. Cranial neuropathies
a. Hoarseness/VC paralysis
b. Tongue atrophy
c. Recurrent aspiration
d. Nystagmus (down beating)
4. Myelopathy
5. Cerebellar dysfunction = nystagmus, scanning speech, truncal ataxia
6. Pain (neck/occipital headache)
b. Type II = Arnold Chiari
i. Features
1. Downward displacement of vermis and tonsils
2. Brainstem malformation with beaked midbrain
3. Spinal myelomeningocoele (usually lumbosacral)
ii. Associations
1. Most have associated hydrocephalus (obstruction of CSF flow through posterior fossa)
2. Stenosis/atresia of cerebral aqueduct
3. Cerebellar dysplasia
iii. Clinical manifestations
1. Nearly always have myelomeningocoele usually detected at birth or antenatally
2. Dysphagia, stridor, aspiration, apnoeic spells, arm weakness
3. Progressive hydrocephalus common in late infancy
5. May have normal intelligence
c. Type III
i. Rare
1. High mortality in infancy – respiratory failure
2. If survive, usually severe neurological impairments
3. Intellectual disability
4. Epilepsy, hypotonia/spasticity
5. UMN and LMN signs
6. Cranial nerve palsies
Demyelinating conditions - list
- Acute disseminated encephalomyelitis (ADEM)
- Transverse myelitis (TM)
- Optic neuritis (ON)
- Neuromyelitis optica spectrum disorder (NMOSD)
- Multiple sclerosis
ADEM and ATM (RCH) - background/sx/outcomes
- Key points
a. ATM manifests with motor, sensory or sphincter dysfunction
b. ADEM is characterised by a polysymptomatic presentation and encephalopathy
c. High dose IV steroids are the mainstay of treatment for both conditions
d. Outcomes are generally good in both conditions
e. Documentation of co-existing brain and/or spine demyelination in both conditions is important, and may have implications for management and prognosis - Background
a. ATM and ADEM are both demyelinating CNS conditions seen in childhood
b. Treatment with IV high dose steroids is widely accepted as the mainstay of treatment for both despite a lack of randomised controlled studies. - Clinical presentation
a. ATM
i. Acute bilateral (but not necessarily symmetric) motor, sensory or sphincter dysfunction
ii. NOTE: brain demyelination has been demonstrated in children with apparently isolated ATM
b. ADEM
i. Multifocal neurological deficits and encephalopathy
ii. Spinal cord involvement in ADEM is reported in 3-25% of cases - Outcome
a. Outcomes in ADEM are usually good, with 57-89% of children making a full neurological recovery
i. However some children may have persistent neuropsychological deficits or learning difficulties
b. ATM - recent experience at RCH showed that 80% of children had a normal to good outcome
c. The risk of further demyelinating events in both ATM and ADEM is low, however, this may vary depending on a number of factors
ADEM and ATM (RCH) - ix/rx
- Investigations
a. Imaging
i. If acute spinal cord dysfunction urgent imaging to exclude tumour, infarction, AVM, abscess, haematoma
ii. MRI brain + spine w/ gadolinium = for both ATM and ADEM confirms diagnosis and excludes DDX - Axial T2 weighting imaging is the most sensitive sequence for ATM
iii. CT brain = often normal, does not exclude ADEM
b. LP = AFTER neuro-imaging
i. MCS, protein glucose
ii. Oligoclonal bands in all children if possible – particularly in those >10 years, short segment or partial myelitis, or presentation atypical of ADEM or ATM (needs to be paired)
iii. Viral PCR = HSV, enterovirus, mycoplasma (others if appropriate eg. varicella)
c. Bloods/other
i. Basic bloods: FBE, UEC, CRP, ESR
ii. Serology - Mycoplasma pneumoniae, CMV, EBV, HSV, VZV ** follow up serology after 3-4 weeks
- ANA
iii. Investigations for disease assoc TM or encephalitis if clinically suspected: - Connective tissue disease: ENA, dsDNA, anti-phospholipid antibodies
- Neurosarcoidosis (ADEM only): serum ACE, CXR, urinalysis
iv. Stool: for M/C/S and viral studies – particularly if present with acute flaccid paralysis for polio
v. Vitamin D (25 hydroxy)
vi. NMO IgG to be tested in ATM and ADEM with spinal cord involvement
vii. Serum MOG antibody (positive in MS) - Management
a. General
i. Attention to bowel, bladder function and pressure care
ii. Monitoring of respiratory function and early involvement of Thoracic physicians particularly in children with cervical or high thoracic cord involvement
iii. In children with ATM consider referral to Urology
iv. Appropriate involvement with Rehabilitation specialists
b. Specific
i. ADEM – require cover for infective encephalitis until proven otherwise IV antibiotics + IV aciclovir
ii. Steroids:
iii. IV Methylprednisolone 15mg/kg (maximum 1g) for 5 days
iv. Oral prednisolone taper over 4-6 weeks
v. IVIG may be considered in specific cases after neurological consultation
ADEM - background, diagnosis
- Epidemiology
a. Peak age 4-8 years; slight male preponderance
b. 3/4 have antecedent event – infections associated with ADEM include influenza, EBV, CMV, varicella, enterovirus, MMR, HSV, mycoplasma pneumoniae; post vaccination have also been reported - Clinical manifestations
a. Encephalopathy
b. Polysymptomatic
i. Motor deficits 80%
ii. Ataxia 50-60%
iii. Cranial nerve signs in up to 50% (optic neuritis usually bilateral) – check for RAPD
iv. Language disturbance (eg. mutism not uncommon)
c. Systemic symptoms common
i. Fever 50%
ii. Vomiting 33%
iii. Headache 40-50%
d. Seizures in 10-30%
e. Concurrent spinal cord involvement in 3-25% - Investigations
a. MRI = lesions typically bilateral, multifocal but asymmetric, and large in size
i. WM abnormalities 90% - subcortical > periventricular WM
vii. Concurrent cord involvement in up to 30%
b. CSF = abnormal in 70% with pleocytosis or increased protein
i. Oligoclonal bands in 0-29% - NOT necessarily indicator of MS
ii. Not always done
c. EEG = non-specific diffuse or less commonly focal slowing of the background activity
i. Epileptiform discharges much less common
a. A first clinical attack with presumed inflammatory or demyelinating cause, with acute or subacute onset that affects multifocal areas of the CNS
i. The clinical presentation is polysymptomatic AND
ii. Must include encephalopathy that may consist of one or more of the following
1. Behavioral change eg. irritability, lethargy
2. Alteration in consciousness eg. somnolence, coma
b. Neuroimaging should show focal or multifocal lesions(s), predominantly involving white matter, without radiological evidence of previous destructive white matter changes
ADEM - treatment, outcomes
- Treatment
a. Spontaneous improvement without treatment is documented
b. Steroids – no RCTs, small paediatric case series IVMP 15 mg/kg/day then oral prednisolone wean over 4 weeks
c. Immunoglobulin = used if no response to steroids
d. Plasmapheresis = used in severe cases if not responsive to steroids or Ig
e. Other = rituximab, cyclophosphamide - Outcomes
a. Attack should be followed by improvement, either clinically or on MRI or both, but there may be residual deficits
b. Clinical symptoms and MRI findings can fluctuate in severity and evolve in the first 3 months following disease
c. A ‘second event’ is defined as the development of new symptoms at least 3 months after the incident illness irrespective of steroid use
d. 57-89% of children make full recovery
e. Mild neurocognitive deficits and behavioural problems not uncommon
i. Children affected at <5 years of age higher risk of cognitive deficits as well as social, behavioural and emotional problems
f. Risk of subsequent diagnosis of multiple sclerosis is low (2-10%)
g. Follow-up imaging
i. Most complete or almost complete resolution of lesions after 3-24 months
ii. However lesions may persist for up to many years, despite clinical recovery
iii. Patients with a diagnosis of monophasic ADEM do not develop a new demyelinating lesion after 3 months
Transverse Myelitis - general
- Key points
a. Inflammatory (demyelinating) lesion of spinal cord
b. Lesions usually span multiple vertebral segments ie. Not really ‘transverse’
i. Term ‘transverse’ retained because of importance of spinal sensory level in making diagnosis
c. Important to assess for other sites of demyelination
i. Encephalopathy (ADEM)
ii. Optic neuritis - Causes
a. Idiopathic ATM
b. Neuromyelitis optica (NMO)
c. Multiple sclerosis (MS)
d. Other systemic disease eg. SLE - Clinical manifestations
a. Weakness, bilateral, usually severe
i. Almost always LL involvement
ii. Sometimes UL involvement
b. Sensory symptoms (2/3) – sensory level
c. Bladder disturbance (2/3) – retention
d. Pain common – back, leg, abdominal
e. UMN signs (unless spinal shock) – hyperreflexia, clonus, up going plantars
f. Absent abdominal reflexes - Investigations
a. Imaging
i. MRI spine – within 24 hours, exclude compressive aetiology - MRI usually abnormal, Rarely changes delayed
- Paediatric idiopathic ATM usually long segment
ii. MRI brain – brain lesions
b. CSF – MCS, protein, glucose, oligoclonal bands
i. 73% pleocytosis, 55% elevated protein
c. Bloods
i. NMO antibody
ii. MOG antibody – particularly associated with phenotypes such as transverse myelitis, NMO, optic neuritis (particularly bilateral), relapsing optic neuritis, relapsing NMO
iii. Serology
iv. Autoantibodies: ANA etc
v. ACE level - Treatment
a. IV steroids = IVMP 15 mg/kg for 5 days with ranitidine Oral steroid wean over 4 weeks
b. IDC if urinary retention
c. Consider plasma exchange in severe cases that fail to respond to high dose corticosteroid treatment - Outcome (RCH series)
a. 50% normal outcome
b. 70-80% normal to good outcome
c. Time to independent ambulation 2 weeks - What is the risk of further demyelinating episodes?
a. Idiopathic ATM = risk of MS diagnosis low
i. Up to 10 % in paediatric myelitis cohorts (but is probably less than this)
Optic Neuritis - background, sx, ddx
- Key points
a. Optic neuritis (ON) = inflammatory demyelinating disorder of the optic nerve that causes acute visual loss
i. Unilateral OR bilateral
b. The pathogenesis of optic neuritis in children is usually demyelinating, but there is a broad DDX
c. Optic neuritis may be an isolated feature, or may be a feature of ADEM, MS or NMO
i. Bilateral severe or recurrent – think MOG (myelin oligodendrocyte glycoprotein)
d. Treatment with steroids hastens visual recovery
e. Visual recovery is good in most patients + can continue for up to 2 years
f. A proportion of children will go on to develop MS - Clinical presentation
a. Visual loss is often profound and may be bilateral
i. Typically develops over hours-days, peak at 1-2 weeks
b. Colour desaturation (especially with red, formally tested with Ishihara (those colour blind circle things))
c. Eye pain – particularly with movement
d. Often para-/post-infectious or post-vaccination - DDx
a. Infective and autoimmune causes of optic neuropathy
b. MS
c. NMO – consider NMO in children with ON+TM or recurrent ON
d. ADEM
Optic Neuritis - assessment
- Clinical assessment
a. Elicit symptoms and signs of optic neuritis
i. Reduced visual acuity (if cannot read Snellen, check finger perception, light perception)
ii. Visual field loss (typically central scotoma, but other defects can occur) - Scotoma: An area of partial alteration in the field of vision consisting of a partially diminished or entirely degenerated visual acuity that is surrounded by a field of normal – or relatively well-preserved – vision
iii. Colour desaturation (Ishihara)
iv. Pain on eye movement (if Retrobulbar neuritis)
v. RAPD = paradoxical dilatation as you swing onto the affected eye
vi. Papillitis (if anterior portion of nerve involved)
b. Disc appearance
i. Normal = Retrobulbar ON
ii. Abnormal = papillitis (ie. involving optic disc – swollen disc, blurred)
iii. Pallor may suggest chronicity
c. Consider issues regarding spectrum of demyelinating diseases including history of preceding infection or vaccine, family history of MS, past history of neurological symptoms or visual impairment, additional current symptoms of encephalopathy (seen with ADEM),transverse myelitis and other focal neurologic deficits.
d. Look for signs that may suggest alternative diagnoses = fever, headache, meningism, inflammation to other parts of eye, joint swellings, cytopaenias, dry eyes and mouth, dysfunction of other organs, systemic symptoms, weight loss, other cranial neuropathies, recent head injury, PHx radiotherapy, drug exposure, micronutrient deficiencies, associated anaemias, longer duration of symptoms, FHx of similar (LHON = mitochondrial, Kjer’s = AD) - Investigations
a. MRI brain + orbits
i. Should occur within 24 hours and before starting steroids – to exclude conditions that may be exacerbated or complicated by steroid therapy (eg. infection, malignancy)
b. Opthal = document severity and exclude DDx
c. Blood tests:
i. Mandatory - FBE + film, inflammatory markers (ESR, CRP)
- ANA
- Blood cultures +/- PCR
- Serology (mycoplasma, toxoplasmosis, syphilis, EBV, CMV, bartonella; if unvaccinated, consider measles, mumps and varicella)
- Lactate
- Oligoclonal bands (paired with CSF)
- Vitamin D
ii. Consider: - dsDNA, ENA, ANCAs
- ACE level, Ca++
- tumour markers (with advice from oncology)
- vitamin B1, B12 and folate levels
- testing for mitochondrial mutations
- NMO antibodies = should be tested if there is a presentation of optic neuritis PLUS transverse myelitis or a recurrent history of either
- Serum MOG antibody
Optic Neuritis - management, outcomes
- Management
a. Our protocol is to treat with steroids unless there is minimal visual impairment (uncommon in children) AND an otherwise normal MRI brain
i. IV methylprednisolone 10-15mg/kg/day for 3-5 days THEN
ii. Oral prednisolone 1mg/kg/day for 1 week THEN
iii. Oral prednisolone 0.5mg/kg/day for 1 week THEN STOP
b. PPI for gastroprotection while on steroids
c. Blood pressure should be monitored while an inpatient - Outcome
a. Estimate that ~85% will recover 6/12 vision; recovery can continue for up to 2 years
b. Recurrent optic neuritis is reported to occur in 3-31%
c. If recurrent – think MS, NMO, MOG
d. Progression to MS
i. Diagnosis of MS is unlikely to be made at first presentation of optic neuritis unless there is a PHx of neurologic symptoms that can be attributed to demyelination, or unless MRI shows lesions disseminated in space AND time
ii. Rates of progression to MS in children vary from 13-46% (OVERALL = 30%)
iii. Highest risk is within the first 2 years after diagnosis
iv. Estimates of risk vary, but risk in children with a monosymptomatic presentation and an MRI that is normal outside of the optic nerve appears very low - Normal MRI brain = 0-7% risk of subsequent MS
v. Risk factors - Abnormal MRI brain at presentation = strongest risk for developing MS (ie. demyelination outside the visual system)
- Age > 12 years
- Presence of oligoclonal bands in the CSF
Neuromyelitis Optica Spectrum Disorder - general
- Key points
a. Characterised by severe attacks of optic neuritis and myelitis
b. Age of onset 31 +/-11 years -> rare in children
c. Index event = isolated myelitis or optic neuritis (up to 90%)
i. Time to second index event 5-6 months on average
d. Relapsing course often leads to severe disability
g. Differentiating features from MS
i. Recovery of visual and spinal cord function is generally not as compete after each episode
ii. ON is more frequently bilateral in NMO than MS - Etiology
a. Idiopathic, Occasional familial cases, Post infectious NMO – HIV, syphilis, chlamydia, variceal, CMV EBV - Clinical manifestation
a. Features of TM + ON
c. ON and TM may occur simultaneously or separate in time by weeks or years - Diagnostic criteria
a. Requires optic neuritis AND transverse myelitis, with 2/3 of:
i. MRI brain not diagnostic of MS
ii. Seropositivity for aquaporin 4Ab
iii. Spine MRI with longitudinally extensive TM involving at least 3 segments - Investigations
a. CSF
i. NMO Ig = target aquaporin 4 Ab = 73% sensitive, 91% specific for NMO
ii. Also test for MOG Ab
iii. Devoid of oligoclonal bands
b. MRI brain spine - Treatment
a. Treat with immunosuppressive agents to prevent relapse
b. Methylprednisolone for 3-5 days followed by taper
c. Rituximab is effective for preventing relapse - Complications
a. Fixed neurological defects affecting visual acuity, visual fields, colour vision, motor and sensory function, balance and bladder/bowel function
Multiple Sclerosis - background, diagnosis
- Key points
a. Rare – estimated 2-5% of MS patients experiencing first symptom <18 years of age
c. Recurrent lesions at a different place in time and space - Clinical manifestations
a. Dependent on where the demyelinating lesions are located
b. Examples:
i. Optic neuritis
ii. Acute partial TM
iii. Ataxia
iv. INO (internuclear ophthalmoplegia) - A disorder of conjugate lateral gaze in which the affected eye shows impairment of adduction. When an attempt is made to gaze contralaterally (relative to the affected eye), the affected eye adducts minimally, if at all. The contralateral eye abducts, however with nystagmus. Additionally, the divergence of the eyes leads to horizontal diplopia.
v. Vertigo
vi. Bladder/bowel dysfunction
c. Polyregional symptoms reported in 30% of patients
d. Encephalopathy is less common: suggests ADEM or possibly NMO - Investigations
a. MRI spine+brain
b. LP
i. Normal or exhibit mild pleocytosis
ii. Oligoclonal bands maybe present – can be negative in 10-60% of patients - Diagnosis
a. Definition = recurrent events of demyelination separated in time and space
i. Relapsing remitting course most common
ii. McDonald criteria for diagnosis - Dissemination in time – eg. 2 attacks or 1 clinical attack now and new lesions on MRI
- Dissemination in space
Multiple Sclerosis - treatment, complications
- Treatment
a. Acute relapse – steroids
b. Symptomatic treatment
c. Disease-modifying therapies
i. First line therapies - Interferon-beta
a. IFN-beta1a (Rebif, Avonex)
b. IFN beta1b (Betaferon)
c. AE = flu-like symptoms, leukopenia, LFTs - Glatiramer acetate (Copaxone)
ii. Second line therapies/ novel therapies - Risk of PML (progressive multifocal encephalopathy) from JC virus (John Cunningham virus aka Human Polyomavirus) (natalizumab, fingolimod, dimethyl fumarate) and other opportunistic infections
- Complications
a. Similarly to adults, children can acquire fixed neurological deficits affecting vision and other cranial nerves, motor and sensory function, balance and bowel/bladder function
Multiple Sclerosis vs ADEM
MS
- Age: >10
- Absent: encephalopathy, fever/vomiting
- Present: family history
- ON: unilateral
- Monosymptomatic
- CSF: oligoclonal bands
- Follow up: new lesions
ADEM
- Age: <10
- Absent: fam hx
- Present: encephalopathy, fever, vomiting
- ON: bilateral
- Polysymptomatic
- CSF: pleocytosis
- Follow up: no new lesions
Bacterial Meningitis - background
- Risk factors
a. Un-immunised
b. Immunodeficiency
i. Defects in complement system (C5-8)
ii. Defects in properdin
iii. Splenic dysfunction or Asplenia
iv. T lymphocyte defects – congenital or acquired increased risk of Listeria
c. Congenital or acquired CSF leak across a mucocutaneous barrier eg. lumbar dural sinus, cranial or midline facial defects (cribriform plate), and middle ear (stapedial foot plate) or inner ear fistula, base of skull fracture
d. Cochlear implant – risk 30x general population - Aetiology
a. Children >2 months
i. Streptococcus pneumoniae
ii. Neisseria meningitidis
iii. Hib (unimmunized children)
b. Children <2 months
i. GBS
ii. E. coli and other GN bacteria
iii. Listeria monocytogenes
c. Immunodeficient
i. Pseudomonas
ii. Staphylococcus aureus, CONS
iii. Salmonella, Listeria
iv. Fungal – Cryptococcus
d. At risk populations
i. Lumbosacral dermal sinus and meningomyelocele associated with staphylococcal, anaerobic and Gram negative enteric bacterial meningitis
ii. CSF shunt infections increase risk of staphylococcus (especially CONS) - Pathogenesis
a. Haematogenous = bacterial colonisation of the nasopharynx > bacteraemia > seeding of meninges
b. Continugous spread = mastoiditis, sinusitis, otitis media, orbital cellulitis, osteomyelitis
Bacterial Meningitis - manifestations, ix
- Clinical manifestations
a. History
i. Infants with meningitis frequently present with non-specific symptoms such as fever, irritability, lethargy, poor feeding, vomiting and diarrhoea
ii. Older children may complain of headache or photophobia
iii. Seizures
iv. Prior antibiotics – clinical presentation may be altered by prior use of antibiotics.
b. Examination
i. In infants, the fontanelle may be full
ii. Neck stiffness may or may not be present (not a reliable sign in young children)
iii. A purpuric rash is suggestive of meningococcal septicaemia
iv. Kernig’s sign: hip flexion with an extended knee causes pain in the back and legs
v. Brudzinski sign: involuntary flexion of the knees and hips are passive flexion of the neck while supine
vi. CSF shunts, spinal and cranial abnormalities (eg dermal sinuses) which may have predisposed a child to meningitis - Investigations
a. LP – see acute medicine for contraindications
b. Blood culture
c. FBE, UEC
Bacterial Meningitis - treatment
a. <2 months = cefotaxime 50 mg/kg Q6H + benzylpenicillin 60 mg/kg Q4H (if >1 month)
b. >2 months = ceftriaxone 50 mg/kg Q6H + dexamethasone 0.15 mg/kg IV Q6H for 4 days
c. If encephalitis suspected = aciclovir 20 mg/kg IV Q8H
d. Targeted therapy
i. N meningitidis = benpen Q4H for 7 days
ii. S pneumoniae = benpen Q4H for 10 days
iii. Hib = ceftriaxone IV
iv. If an organism is not isolated but CSF pleocytosis is present – minimum 7 days with IV ceftriaxone
v. Prolonged IV therapy require for neonatal and GN bacillary meningitis
e. Note
i. Benzylpenicillin can be substituted with amoxycillin 50mg/kg iv
ii. Cefotaxime can be substituted with Ceftriaxone 100 mg/kg (max 2gm) iv daily in children > 1 month
iii. Empiric use of vancomycin is not currently recommended for pneumococcal meningitis in Victoria
iv. Delay in antibiotics is associated with poorer outcomes.
f. Steroids
i. Current evidence suggests that steroids may reduce the risk of hearing loss in bacterial meningitis
ii. Consider giving Dexamethasone to children > 2 months of age 15 minutes prior to parenteral antibiotics or, if this is not possible, within one hour of receiving their first dose of antibiotics: 0.15mg/kg IV. Consider giving steroids at the time of lumbar puncture if the clinical suspicion of meningitis is high
iii. Steroids should be ceased if a decision is made to cease antibiotic treatment for meningitis before 4 days (eg CSF microscopy not suggestive, CSF cultures negative at 48 hours)
iv. Steroids are not recommended in neonates due to concern regarding effects on neurodevelopment
Bacterial Meningitis - complications/fup/prognosis
- Complications
a. Seizures – manage with BDZ, phenytoin
b. Subdural effusion
c. Other foci of suppuration
d. Parameningeal focus
e. DIC
f. Severe neurological sequelae 10-20% = hearing loss, mental retardation, recurrent seizure, delay in acquisition of speech, visual impairment & behavioral problems (50% have subtle neurobehavioral issues)
i. Sensorineural hearing loss most common sequelae (30% of pneumococcal infection)
ii. Invasive meningococcal disease mortality still 10% - Follow-up
a. Formal audiology appointment 6-8 weeks after discharge
b. Neurodevelopmental surveillance - Prophylaxis
a. Meningococcal chemoprophylaxis
b. Indications
i. Index case – if treated only with penicillin
ii. All intimate, household or daycare contacts who have been exposed to index case within 10 days of onset
iii. Any person who gave mouth to mouth resuscitation
c. Drugs
i. Rifampicin – discolouration of tears, urine and contact lenses, skin rash, GI disturbance; contraindicated in those with severe liver disease or on OCP (negates the effect)
ii. Ceftriaxone or ciprofloxacin
Viral Meningitis - general
- Definition
a. Febrile illness with clinical signs and symptoms of meningeal irritation
b. No associated neurologic dysfunction
c. No evidence of bacterial pathogens in the CSF in a patient who has not received antibiotics - Aetiology
a. Enteroviruses = poliovirus, coxsackievirus, echovirus = most common
b. Paraechovirus
c. Arboviruses
d. Herpesviruses
i. HSV 1 – important cause of severe, sporadic encephalitis
ii. HSV 2 – neonates who contract virus from mothers
iii. VZV – cerebellar ataxia to severe encephalitis
iv. CMV – in immunocompromised hosts
v. HHV 6 – in immunocompromised hosts - Clinical manifestations
a. As for meningitis but usually less severe
b. Features suggestive of enterovirus = conjunctivitis, pharyngitis, rash, herpangina, hand-foot-mouth disease - Treatment
a. Treat as bacterial until it has been excluded
b. Requires negative CSF culture - Prognosis
a. Complete recovery
b. Some may have fatigue, irritability, decreased concentration, muscle weakness and spasm for a period of time
Eosinophilic Meningitis - general
- Key points
a. >10 eosinophils/mm3 of CSF and/or accounting for >10% of CSF leukocytes - Aetiology
a. Infection
i. Parasites - Angiostrongylus cantonesis
- Baylisascaris procyonis
- Gnathostoma spinigerum
ii. Bacteria
iii. Virus
iv. Fungus – Coccidioides
b. Non-Infection
i. Malignancy – NHL, Hodgkin, Eosinophilic leukaemia
ii. Drugs – ibuprofen, ciprofloxacin, intraventricular antibiotics
iii. Others – VP shunts, hypereosinophilic syndrome - Investigations
a. CSF
i. Normal to high opening pressure
ii. Cell count 20-5000
iii. >10% eosinophils
iv. Glucose normal
v. Protein increased - Treatment
a. No effective
b. Supportive care
c. Repeat LP s
Amoebic Meningitis - general
• Granulomatous amoebic encephalitis = Acanthomoeba spp and Balamuthia spp
o Most often subacute or chronic disease, usually fatal sometime after neurological signs appear
• Primary amoebic meningoencephalitis = Naegleria fowleri often rapidly progressive
• Presents with – fever, headache, focal neuro signs, behavioural change, lethargy, ataxia, seizures, CN palsy, altered mental status
• CSF pleocytosis with lymphocytic predominance, increased protein, low glucose – or can be normal
• Cysts and trophozoites may be seen
• Biopsy may be required
• Treatment not well defined
Meningitis - CSF interpretation
General principles
- “normal” neutrophils = 0
- normal to have a few lymphocytes
- “normal” CSF and negative Gram stain does not rule out bacterial meningitis (Gram stain negative in up to 60% even without prior antis)
- correcting for RBCs is inaccurate and not validated, if concerns for meningitis need to treat
Bacterial (usually)
- neuts >100
- lymphocytes <100
- protein high, glucose low
Viral (usually)
- neuts <100
- lymphs >100
- low protein, normal glucose
TB
- neuts <100
- lymphs >100
- normal protein, low glucose
Encephalitis - general
- Key points
a. Encephalitis = inflammation of the brain parenchyma associated with neurological dysfunction - Aetiology
a. Enterovirus (most common)
b. HSV
c. Other herpesviruses – EBV, CMV, HHV6, VZV
d. Arboviruses
e. Bacteria, fungi, parasites - Clinical manifestations
a. Altered conscious state = decreased level of consciousness, lethargy, personality change, unusual behaviour
b. Focal neurological signs
c. Seizures
d. Associated symptoms = fever, headache, nausea, vomiting - Investigations
a. Blood culture
b. CSF
c. Urine and serum toxicology, metabolic studies, anti-NMDA = if indicated
d. Imaging = temporal lobe localisation in HSV encephalitis
e. EEG = temporal lobe slowing in HSV encephalitis - Treatment
a. Aciclovir
b. If proven HSV encephalitis – treatment for 21 days - Prognosis
a. Poor outcome associated with
i. Coma, convulsion or focal neurological findings in acute phase
ii. Young age
iii. Need for ICU
iv. HSV encephalitis
v. Diffusion restriction on MRI
b. Neurological sequelae – variable
CNS Abscess - general
- Key points
a. Occur in children of any age – most common 4-8 years - Pathogenesis
c. Majority single – 30% multiple
d. Pathogenesis unknown in 10-15% of cases
e. Day 1-9 – cerebritis with liquefaction
f. Day 10-14 – well circumscribed capsule forms
g. Direct spread 50% = single abscess
i. Infection – most common source - OM/mastoiditis/sinusitis = temporal lobe/ cerebellum
- Meningitis/dental infection/orbital cellulitis = frontal lobe
ii. Trauma / foreign body (shunt)
iii. Post-operative
h. Haematogenous spread 50% = multiple abscesses distribution MCA
i. Usually develop at grey-white matter junction where infarction damages BBB
ii. Chronic pulmonary infection (lung abscess, empyema)
iii. Cyanotic congenital heart disease – especially TOF as blood bypasses phagocytic filtering action of pulmonary capillary bed
iv. Bacterial endocarditis - Aetiology
a. Streptococci (anaerobic and aerobic) – 60-70% - Clinical manifestations
a. Early stage of cerebritis and abscess formation – low-grade fever, headache, lethargy
b. Progress to vomiting, severe headache, seizures, papilledema, focal neurological signs, coma - Investigations
a. Blood culture
b. CSF – rarely positive
i. Often contraindicated due to risk of transtentorial herniation
c. Imaging = MRI with contrast Ix of choice (differentiate abscess from neoplasm) - Treatment
a. Antibiotics = if <2cm and <2 weeks in duration, no signs of raised ICP, child neurologically intact
i. Metronidazole + ceftriaxone/cefotaxime
b. Neurosurgical intervention
i. Abscess >2.5 cm
ii. Gas is present in the abscess
iii. Multiloculated
iv. Located in the posterior fossa
v. Fungus suspected
c. Usually treated with IV antibiotics for 4-6 weeks - Mortality = 5-10%
- Long-term sequelae
a. Hemiparesis
b. Seizures
c. Hydrocephalus
d. Cranial nerve abnormalities
e. Behaviour and learning problems
Stroke - general background
- Key points
a. Childhood stroke is more common than brain tumours – top 10 cause of death in childhood
b. Often delays in diagnosis as acute neurological deficits may be attributed to stroke mimickers like migraine, encephalitis or seizure related Todd’s paresis
- Urgent brain imaging is critical to confirm stroke diagnosis and guide management.
- Early involvement of a paediatric Neurology team is essential to guide assessment and acute management of suspected childhood stroke.
- Reperfusion therapies are time critical: alteplase within 4.5 hours, and endovascular clot retrieval within 6 hours of symptom onset.
- Childhood stroke has a mortality rate of 5-10%. More than half of the survivors have long-term neurological impairment and 10-20% suffer recurrent strokes
- Arterial ischaemic stroke is the most common subtype, accounting for just over half of all strokes - Subtypes
a. Acute arterial ischaemic stroke
b. CV sinovenous thrombosis
c. Haemorrhagic stroke - Aetiology
a. Arteriopathies = major cause of arterial stroke (accounting for 50%)
b. Cardiac disease (25%)
c. Congenital or acquired Thrombophilic disorders
d. NOTE: cause of perinatal arterial stroke usually unknown
Stroke - general work up
- History and examination
a. Specifically ask about
i. Recent head/neck injury, chiropractic neck manipulation
ii. Varicella infection in the last 6-12 months
iii. Migraine
iv. OCP or illicit drug use in adolescents
v. Family history of early onset ( < age 55) stroke, heart attack or venous thrombosis
vi. Recent ENT/head and neck infection in suspected sinovenous thrombosis
b. Specifically examine for cardiac murmurs, carotid or cranial bruits
c. Suspect stroke in newborns with unexplained seizures or focal neurological signs
d. Suspect stroke in older infants or children with sudden onset of focal neurological deficits reaching maximal severity within hours.
Red flag features
Children presenting with sudden onset of the following features are at high risk of stroke and should undergo immediate neurological assessment and be considered for urgent neuroimaging:
- Focal limb or facial weakness*
- Visual or speech disturbance*
- Limb incoordination or ataxia*
- Headache with other neurological signs or symptoms^
- Altered mental state^
- Signs of raised intracranial pressure^
- New onset seizures associated with persistent neurological signs or symptoms
(*Arterial ishaemic stroke more likely; ^Haemorrhagic stroke more likely)
- Investigations
Brain imaging
- In suspected haemorrhagic stroke, urgent non-contrast CT should be performed
- In suspected arterial ischaemic stroke, urgent brain MRI and MRA should be performed
- Where urgent MRI is not possible within 30 minutes, CT, including CT angiography should be performed
Immediate investigations to determine eligibility for reperfusion therapies
- FBE, coagulation profile, UEC, glucose, LFTs, blood group and hold
Subsequent investigations to identify underlying causes of confirmed stroke
- ECG and echocardiography
- Prothrombotic markers and serum homocysteine
i. Anticardiolipin (ACLA), lupus anticoagulant (antiphospholipid antibodies)
ii. Antithrombin, protein C, protein S
iii. Activated protein C resistance
iv. Factor V Leiden, Prothrombin gene 20210A mutation
v. Serum homocysteine
Stroke - general treatment
a. Initial stabilisation
i. Refer to neurosurgeons if haemorrhage or evidence of posterior circulation or large anterior circulation dissection, or deteriorating conscious state
ii. Establish IV access + give IV fluids to maintain BP
iii. Avoid hypotension
iv. Maintain normoglycaemia
v. Prevent hypothermia
vi. Load with IV phenytoin if seizures
vii. NBM until swallowing assessed
viii. Supportive care = avoid distress, hypotension, dehydration and hypocapnoea – particularly important with known arterial stenosis or Moyamoya
b. Arterial ischaemic stroke
i. Reperfusion therapies (updated 2021)
1. Acute treatment decisions should be coordinated by the Neurology team in consultation with Emergency and Haematology teams
2. Assessment of initial stroke symptom severity using the Pediatric NIH Stroke Scale must be performed in consultation with the Neurology team before reperfusion therapy is commenced
3. Alteplase (recombinant tissue plasminogen activator) may be appropriate in specific children.
a. Potential eligibility criteria include:
b. 2 to 17 years of age
c. radiologically confirmed arterial stroke with absence of haemorrhage
d. Pediatric NIH Stroke Scale score >3 and <24, with symptoms that are not improving
e. time from symptom onset <4.5 hours
4. Administration: IV infusion - Total dose is 0.9 mg/kg (maximum 90 mg):
a. bolus of 0.09 mg/kg
b. then 0.81 mg/kg infused over 60 minutes
5. Absolute contraindications
a. Known cerebral arterial venous malformation, aneurysm, or CNS neoplasm
b. Known allergy to Alteplase
ii. Endovascular therapies may be appropriate in some children with radiologically diagnosed ischaemic stroke (discuss with Neurology)
Anticoagulant and antithrombotic therapy:
- In children with arterial ischaemic stroke in whom reperfusion therapy is not given, or as secondary prevention:
- Anticoagulation and antiplatelet therapy are indicated after the exclusion of haemorrhage on brain imaging
- Anticoagulation and antiplatelet therapy should not be administered within 24 hours of receiving alteplase
iii. Initial management
1. Non-sickle cell disease – UFH (unfractionated heparin)
iv. Subsequent management
1. Cardioembolic stroke and dissection excluded: aspirin (1-5 mg/kg/day) for 2 years
2. Cardioembolic stroke and dissection confirmed: anticoagulant therapy with LMWH heparin or warfarin for at least 6 weeks
3. Children with sickle cell disease – IV hydration and exchange transfusion to reduce HbS level to <30% total Hb
4. Moyamoya – referred to neurosurgeon for consideration of revascularization
5. If recurrent strokes or TIAs while on aspirin prophylaxis clopidogrel, aspirin-dipyrimadole or anticoagulant therapy
v. Neonatal
1. Aspirin or anticoagulant for 6-12 weeks for cardio-embolic AIS
2. Anticoagulation or aspirin for non-cardioembolic AIS not recommended unless recurrent events
c. Cerebral sinovenous thrombosis
i. Without significant intracranial haemorrhage
1. Anticoagulation for 3/12 with UFH, or LMWH and subsequently LMWH or warfarin for 3/12 (aim for INR of 2.5
2. After 3 months of therapy if incomplete radiological canalization of CVST or ongoing symptoms, further 3/12 of anticoagulation
ii. Neonatal SVT without significant intracranial haemorrhage
1. Anticoagulation initially with UFH, o LMWH and subsequently LMWH or warfarin for minimum of 6/52 and no longer than 3/12
iii. SVT with significant intracranial haemorrhage
1. Neurosurg referral
Acute Arterial Ischaemic Stroke - background
- Key points
a. Acute ischaemic stroke (AIS) = focal infarction resulting from occlusion of arteries
b. Diagnosis often delayed
d. The acute onset of a focal neurological deficit in a child is stroke until proven otherwise - Pathogenesis
a. Arterial blood reaches brain via anterior (internal carotid) and posterior (vertebrobasilar) circulations converging at the circle of Willis
b. Strokes most often involve the MCA territory - Risk factors
a. Arteriopathy = leading cause of childhood AIS, present in >50% of children
i. Transient cerebral arteriopathy
ii. Post-varicella and other viruses angiopathy
iii. Systemic/secondary vasculitis (eg. Takayasu)
iv. Moyamoya disease = idiopathic or associated with other conditions (NF type 1, trisomy 21, Alagille syndrome, sickle cell anaemia, chromosomal deletions/duplications, post-irradiation)
v. Fibromuscular dysplasia
vi. Traumatic or spontaneous dissection
vii. Vasospasm
viii. Congenital arterial hypoplasia (PHACE)
b. Cardiac = 25% of childhood AIS
i. Congenital heart disease
1. PFO – paradoxical venous thromboembolism
ii. Cardiac catheterisation + surgery
iii. Arrythmia, valvular heart disease, endocarditis, cardiomyopathy
iv. Intracardiac lesions (atrial myxoma)
c. Haematological
i. Sickle cell anaemia
ii. Iron deficiency anaemia
iii. Inherited prothrombotic = factor V Leiden, prothrombin gene mutation 20210A
iv. Acquired prothrombotic = protein C/S deficiency, antithrombin III deficiency, lipoprotein A, APLS, oral contraceptive, pregnancy
d. Other
i. Acute systemic illness
ii. Chronic systemic illness
iii. Illicit drugs
iv. MANY others
Acute Arterial Ischaemic Stroke - sx/ix/rx
- Clinical manifestation
a. Hemiparesis – most common
b. Other presenting features – acute visual, speech, sensory or balance deficits - Investigations
a. CT = can demonstrate mature AIS and exclude haemorrhage
b. MRI = Ix of choice
i. Diffusion weighted MRI can demonstrate AIS within minutes of onset up to 7 days post-onset
c. MRA = diagnose vascular occlusion and suggest possible arteriopathy - Treatment
a. Antithrombotic strategies
- d/w neuro re thrombolytic option
b. Neuroprotective measures = control BG, temperature an seizures
c. Disease specific treatments
i. Transfusion therapy in sickle cell disease
ii. Immunosuppression in vasculitis
iii. Revascularization in Moyamoya
d. Secondary stroke prevention
e. Rehabilitation - Prognosis
a. Recurrent stroke 10-50% depending on cause, death 6-10%
b. Neurological deficit in 60-70%
Perinatal Arterial Ischaemic Stroke - general
- Key points
a. Very common, differs from childhood stroke and has 2 distinct clinical presentations
b. Acute symptomatic neonatal AIS
i. Presents with focal seizures at 24-28 hours of life
ii. MRI diffusion abnormalities in an arterial territory confirm recent infarction
c. Late presentation
i. Infants are asymptomatic at birth and present later in infancy with signs of early hand preference and hemiparesis
ii. Hand dominance within the first year of life is abnormal
iii. Imaging reveals focal encephalomalacia in an arterial territory, typically large MCA lesion - Management
a. In acute neonatal AIS seizure control is important
b. Antithrombotic agents are rarely required (exception: cardiac thromboembolism) - Outcome
a. Poor outcome
b. Most children have lifelong disability
c. Perinatal stroke accounts for most cases of Hemiparetic CP
d. Additional morbidity seen in 25% - disorders of language, learning, cognition and behaviour, long-term epilepsy
e. Stroke recurrence for both the child and subsequent pregnancies are extremely low
Cerebral Sinvenous Thrombosis - general
- Key points
a. Cerebral venous drainage occurs via the cerebral sinovenous system
b. Includes superficial (cortical veins, superior sagittal sinus) and deep (internal cerebral veins, straight sinus) system that converge at the torcula to exit via the paired transverse and sigmoid sinuses and jugular veins
c. Consequences of CVST
i. Increased intracranial pressure
ii. Cerebral oedema
iii. Venous haemorrhage or infarction (50%)
d. More common in children than adults
e. Most common in neonates
f. Clinical presentation typically gradual, variable and nonspecific compared with AIS - Risk factors
a. Blood coagulation
i. Prothrombotic conditions
ii. Dehydration (eg. gastro, neonatal FTT)
iii. Iron deficiency anaemia
iv. Drugs and toxins (eg. L-asparaginase (ALL), oral contraceptives)
v. Acute systemic illnesses (eg. sepsis, DIC)
vi. Chronic systemic illnesses (eg. IBD, SLE, leukaemia)
vii. Nephrotic syndrome
viii. Inborn errors of metabolism
b. Blood vessel
i. Infection/thrombophlebitis - Lemierre syndrome
- Sepsis
ii. Trauma = skull fracture, closed head trauma
iii. Compression = birth, occipital bone compression in neonates
iv. Iatrogenic = neurosurgery, jugular lines, ECMO
v. Venous malformation (eg. dural AV fistula) - Clinical presentation
a. Neonates = encephalopathy and seizures
b. Children = symptoms mimicking idiopathic intracranial hypertension
i. Progressive headache, papilledema, diplopia secondary to CNVI palsy, or with acute focal deficits
ii. Seizures, lethargy and confusion are common - Investigations
a. CT venography or MR venography = required for diagnosis - Management
a. Anticoagulation
i. UFH or LMWH in most children
- 3-6 months (reimage 3 months)
v. Children with persistent risk factors may require long-term anticoagulation
vi. Note: optic neuropathy secondary to increased ICP is an important and easily missed complication of CVST - Regular opthal examination to measure ICP is required
- Measures to reduce ICP may be required – acetazolamide, serial LP
Haemorrhagic Stroke - general
- Key points
a. HS includes non-traumatic ICH and is classified by the intracranial compartment containing the haemorrhage
b. Intraparenchymal bleeds may occur anywhere, IVH may be isolated or an extension of intraparenchymal bleeding
c. Bleeding outside the brain may occur in subarachnoid, subdural or epidural space - Risk factors
a. Vascular disorder (vascular malformations, hereditary haemorrhagic telangiectasia, aneurysm (less common in children), Moyamoya, vasculitis, neoplasm, drugs, cerebral sinovenous thrombosis)
b. Blood disorder (ITP, HUS, liver failure and coagulopathy, vit K deficiency, DIC)
c. Trauma
i. Middle meningeal artery injury – epidural haematoma
ii. Bridging vein injury – subdural haematoma
iii. SAH
iv. Haemorrhagic contusions (coup and contre-coup)
v. NAI (subdural haematomas of different ages)
vi. Iatrogenic
vii. Rupture of arachnoid cyst - Clinical presentation
a. Varies depending on location, cause and rate of bleeding
b. May feature thunder-clap headache, loss of consciousness and nuchal rigidity
c. Focal neurological deficit and seizures
d. Can be rapidly fatal
e. If bleeds associated with vascular malformations – pulsatile tinnitus, cranial bruit, macrocephaly and high output HF may be present - Investigations
a. CT = highly sensitive to acute HS
b. LP = may be required to exclude subarachnoid haemorrhage
c. MRI = highly sensitive to small amounts of acute and/or chronic haemorrhage test of choice
d. Angiography by CT or MRI = often required to exclude underlying vascular abnormalities - Management = Urgent neurosurgical intervention
a. Reversal of anticoagulation (eg. FFP, vitamin K)
b. Definitive repair or removal of vascular malformation
c. Recurrence risk for those with structural lesions – serial imaging may be required - Outcome
a. Not well studied – depend on size location and etiology
b. Higher mortality than AIS
c. Long-term deficits less common
Neonatal haemorrhagic stroke - general
• Cranial USS can detect many neonatal parenchymal bleeds, especially in preterm infant (bleeds usually centrally within the cranium and include germinal matrix bleeding and IVH)
o Germinal matrix injury or bleeding may also occur in utero resulting in periventricular venous infarction that becomes symptomatic in later infancy as congenital hemiparesis
• Subarachnoid and subdural blood may by imaged in up to 25% of normal term newborns
• Term HS is poorly studied
• Term IVH is often secondary to deep CVST
Differentials of Stroke
Migraine
- evolving/marching symptoms, short, complete resolution, personal/fam hx
- normal imaging
Seizure
- positive symptoms, Todds paralysis
- normal imaging or underlying cause e.g. malformation
Infection
- fever, encephalopathy, gradual onset, meningism
Demyelination
- gradual onset, multifocal, encephalopathy, optic neuritis or TM
Hypoglycaemia
- risk factors, meals, systemic symptoms
HIE (watershed infarction)
- risk factors, bilateral
- bilateral, symmetric restriction diffusion in border zones between major arteries (watershed zones)
Hypertensive encephalopathy (PRES = posterior reversible encephalopathy syndrome) - HTN, bilateral visual symptoms, encephalopathy
Vestibulopathy
- vertigo, imbalance, no weakness, gradual onset
- normal imaging
Inborn error metabolism (IEM)
- pre-existing delays/regressions, multisystem disease, abnormal biochemical profile
Acute cerebellar ataxia
- sudden onset bilateral symmetric ataxia, post viral
- normal imaging
Channelopathy
- syndromic, not localised, gradual
- normal imaging
Alternating hemiplegia
- history of contralateral events, choreoathetosis, dystonia
- normal imaging
Movement Disorders - general overview
- Key points
a. Conditions that affect the speed, fluency, quality and ease of movement
b. Usually affect TONE and POSTURE
c. Generally restricted to disorders secondary to pathology in the brain
i. Basal ganglia – extrapyramidal [generally pathology in BG referred to as ‘movement disorder’] (involuntary)
ii. Corticospinal – pyramidal (voluntary)
iii. Cerebellum
d. What do BG do?
i. Set up the muscle tone and posture upon which voluntary movements can occur
ii. Extrapyramidal and pyramidal work together to produce normal movements
iii. Basal ganglia also involved with behaviour and cognition ie. psychiatric disturbances may co-exist (think Tourettes/ Huntington’s/ Parkinson’s) - Classification
a. Abnormal movements may be divided into
i. Voluntary and involuntary
ii. Positive and negative - Neurotransmitters involved
a. Acetylcholine
b. Dopamine
c. GABA
d. Glutamine
e. Substance P - Aetiology
a. Infections = primary, parainfectious, autoimmune
b. Ischaemia = HIE, stroke
c. Trauma
d. Tumours = neoplastic, paraneoplastic
e. Metabolic = neurotransmitter disorders, mitochondrial, Wilsons, PKAN
f. Autoimmune = SLE
g. Medications = anticonvulsants, antipsychotics - Positive movement disorders (hyperkinetic)
- rhythmic = tremors
- athetosis (nonrhythmic, slow)
- dystonia (nonrhythmic, sustained)
- tics (nonrhythmic, rapid, suppressible)
- hemiballismus, chorea, myoclonus (nonrhythmic, rapid, nonsuppressible) - Negative (bradykinetic)
a. Rigidity = inability of the muscles to relax normally
b. Akinesia = inability to initiate movement
c. Hypokinesia = reduction in the amount of spontaneous movement
d. Bradykinesia = slowness of movement
Dyskinesia
Dyskinesia is a general term for any abnormal involuntary movement.
Akinesia means absence of movement.
Bradykinesia means slowness of movement.
Hypokinesia means decreased amplitude or range of movement.
Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements or a combination of both. Hyperkinesia is a state of excessive restlessness.
Tremor is an oscillation that is usually rhythmical and regular that affects one or more body parts, such as the arms, legs, neck, tongue, chin or vocal cords. Tremor is produced by rhythmic alternating or simultaneous contractions of opposing muscles.
Bradykinetic Movement Disorders
• Frequently accompanied by rigidity, postural instability, and loss of automatic associated movements
• Include:
o Parkinson disease
o Wilson disease
o Huntington disease
o Neurodegeneration with iron accumulation
Chorea - general
- Key points
a. Nonrhythmic, jerky, rapid + nonsuppressible movements, primarily in distal muscles or face.
b. Occurs both at rest and with action
c. Increase with stress and disappears with sleep
d. Primary and secondary causes - Causes
a. Primary
i. Huntington’s disease – rarely presents in childhood
ii. Neuroacanthocytosis
iii. Ataxia telangiectasia
iv. Spinocerebellar ataxia
b. Acquired
i. Sydenham chorea
ii. Autoimmune = SLE, NMDA
iii. Endocrine = Hyperthyroidism, hypoparathyroidism
iv. Wilson disease
v. CNS infections - toxoplasmosis, Neurosyphilis, viral encephalitis
vi. Structural lesions in basal ganglia – stroke, mass lesions, multiple sclerosis
vii. Toxins
viii. Medications – AED, antipsychotics - Treatment
a. Valproate
b. BDZ
c. Haloperidol
d. Chlorpromazine
e. Penicillin
Athetosis - general
Uptodate: Athetosis is defined as “a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture” and thus represents a form of slow chorea.
- Key points
a. Slow, writhing movements that involve the same body parts
b. May occur at rest
c. Worsened by voluntary movement
d. Usually occurs in conjunction with chorea or dystonia - Causes
a. HIE (CP)
b. PKU
c. Metabolic = Wilsons, PKU, Niemann-Pick, PKAN
d. Mitochondrial = Leigh disease
e. Kernicterus
f. Medications
Dystonia - general
Uptodate: Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both; dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation.
- Key points
a. Non-rhythmic, sustained muscle contraction (unbalanced), frequently causing distorted body posture patterned, twisting, tremulous
b. WORSENED by voluntary action - Causes
a. Primary (inherited dystonias)
i. Idiopathic torsion dystonia (DYT1)
ii. Paroxysmal torticollis
iii. Segawa disease (DRD) (DYT5a, dopamine responsive)
iv. Paroxysmal
b. Secondary
i. HIE
- CP -> 10-15% have dyskinetic form with dystonia and chorea rather than spasticity
ii. Huntington
iii. PKAN
iv. Wilson
v. Niemann-Pick
vi. Glutaric aciduria
vii. Medications
viii. Hyperthyroidism
Metabolic disorders: disorders of monoamine neurotransmitter metabolism, Wilsons, pantothenate kinase associated neurodegeneration (PKAN)
Treatment
- trial levodopa (?dopamine responsive dystonia -> if effective, continue), if no response:
- botox can be used for focal dystonia
- anticholinergics (eg benztropine)
- can add benzodiazepine (clonazepam, diazepam, baclofen)
- surgical options e.g. deep brain stimulation
h. When you think functional, think dystonia when you think dystonia, think functional
Drugs causing dystonia
Dopamine blocking agents, antipsychotics, antiemetics
Acute dystonic reactions
- within days of starting medication
- torticollis, oculogyric crisis (characterized by a prolonged involuntary upward deviation of the eyes), tongue protrusion, laryngospasm
Neuroepileptic malignant syndrome
- within a few days of starting/increasing or following withdrawal of med
- fever, tachycardia, diaphoresis, delirium, dystonia
Tardive dyskinesia
- chronic (3+ months of use)
- much less frequent in children
- causes repetitive, involuntary movements, such as grimacing and eye blinking
Tremor - general
- Types
a. Static/Resting tremor
i. Present at rest, disappears with action
ii. Causes: Wilson’s, Parkinson’s, Huntington’s, Hallervorden-Spatz
b. Postural tremor
i. Most notable when arms outstretched forwards, but can occur through a range of movement/during goal-directed activity
ii. Causes: thyrotoxicosis, pheochromocytes, familial/essential tremor, physiological tremor, Wilson’s disease
c. Intention tremor
i. Marked at end points of movement, but not present during course of movement
ii. Causes: cerebellar disease (including Wilson’s disease) - Causes
a. Benign essential
b. Drugs = amphetamines, valproate, TCAs, caffeine, SSRIs
i. Amphetamines
ii. Valproate
iii. TCAs
iv. Caffeine
v. SSRIs
c. Metabolic/endocrine
i. Hypoglycaemia, hypocalcaemia, hypoMg, B12 deficiency
ii. Hyperthyroidism
iii. PKU, galactosaemia
d. Degenerative diseases
i. Mitochondrial diseases eg. Leigh syndrome
ii. Wilson’s disease
iii. Ataxia telangiectasia
iv. Juvenile PD
e. Peripheral neuropathies eg. SMA
f. Psychogenic and medically unexplained
g. Bobble-headed doll- IIIrd V lesions
h. Spasms nutans - episodic abnormal head posturing with nystagmus - Treatment
a. Beta blockers
b. Clonidine Primadone
c. DBS (Deep brain stimulation)
Essential tremor - general
Key points
- 5% prevalence, 50% AD, variable presentation
Manifestations
- most commonly affects distal upper extremities
- most apparent at end of goal directed activity (drinking glass of water, finger-nose) and disappears at rest
- begins in childhood, slowly progressive
Diagnosis
Core criteria
- bilateral action tremor of hands/forearms, not present at rest
- absence of other cognitive signs
- may have isolated head tremor with no signs of dystonia
- seondary criteria: long duration >3 years, positive famhx, beneficial response to alcohol
Treatment
- propranolol sometimes used
Myoclonus - general
- Key points
a. Non rhythmic, rapid, nonsuppressible shock like twitches
b. Can be cortical + subcortical - Causes
a. Physiological (sleep)
b. Epilepsy
c. HIE
d. Autoimmune
i. Opsoclonus/ myoclonus
e. Metabolic
i. Tay Sachs
ii. Wilsons
iii. NCL
iv. Mitochondrial
f. Medications - Management
a. Benzos
b. Valproate
c. Keppra
Tics - general
- Key points
a. Idiosyncratic, non-rhythmic, rapid, suppressible and repetitive movements
b. Usually diminished in sleep - Causes
a. Idiopathic
i. Simple
ii. Tourette = vocal and motor
b. Secondary
i. Sydenham chorea
ii. Post HIE
iii. Medications - Treatment
a. Reassurance
b. Clonidine
c. Haloperidol
d. Pimizoide - The main disabilities in tic disorders are not tics
Tourette syndrome - general
Key points
- 5/10,000 M>F, usually presents <7years
Diagnosis
- multiple vocal and motor tics, nearly every day for >1 year, no more than 3 months tic free
Associations
- ADHD (50%), OCD (30%), ODD (15%), learning disorder (25%)
Treatment
- antidopaminergics (fluphenazine, risperidone, tetrabenazine)
- alpha adrenergic agonist (clonidine)
- topiramate
- botox
- habit reversal thinking
Hemiballismus - general
- Key points
a. Nonrhythmic, rapid, nonsuppressible violent / flinging movements
b. Usually unilateral
c. Often proximal arm - Definitions
a. Chorea = ongoing random appearing sequence of movement fragments
b. Athetosis = slow continuous involuntary writhing movement
c. Ballismus = chorea that effects proximal joints such as the shoulders/ hips large amplitude movements of the limbs with flinging/ flailing quality - Causes
a. Physiologic – chorea normal up until 8 months of age
b. Cerebral palsy
c. Sydenham Chorea: 1-8 months post infection
d. Inherited
i. Huntington disease
ii. Benign hereditary chorea: AD disorder, mutations in NKX2-1 gene
iii. Lesch Nyhan syndrome: X linked disorder of purine breakdown, leading to excessive uric acid – choreathetosis, spasticity, chorea, biting and aggressive behaviours
Ataxias - general
- Key points
a. Ataxia = disturbance in the smooth, accurate coordination of movement
i. Most commonly manifested as an unsteady gait
b. Usually results from cerebellar dysfunction
c. Most common causes
i. Acute cerebellar ataxia – most common
ii. Drug intoxication
iii. Guillain-Barre - Aetiology
a. Life-threatening
i. Tumours – particularly posterior fossa
ii. Intracerebral haemorrhage
iii. Stroke
iv. Infection - Cerebellar abscesses (contiguous spread from otitis media or mastoiditis)
- Brainstem encephalitis – rare cause with high morbidity
a. Causes include Listeria monocytogenes, Lyme disease, EBV and HSV - ADEM
b. Common conditions
i. Acute cerebellar ataxia
ii. Guillain-Barre syndrome
iii. Toxic exposure
iv. Labyrinthitis
v. Migraine syndromes and BPPV
vi. Trauma - Evaluation
a. History
b. Examination
i. Bulging anterior fontanelle raised ICP
ii. Ipsilateral head tilt posterior fossa tumour
iii. Nystagmus vestibular, cerebellar or brainstem disorders; opsoclonus associated with neuroblastoma
iv. Otitis media and hearing loss acute labyrinthitis
v. Meningitis CNS
vi. Healing rash/ viral exanthem antecedent infection
vii. Cerebellar signs
c. Investigations
i. Toxicological screen
ii. BSL
iii. Metabolic
iv. CSF
v. Imaging
Cerebellar signs
vii. Cerebellar signs
- Wide based, unsteady, lurching or staggering gait
- Dysarthria
- Difficulty maintaining truncal position – titubation
- Dysmetria – finger nose
- Dysdiadochokinesia – difficulty with rapid alternating movements
- Vermis (midline) = dysarthria, truncal titubation, gait abnormalities
- Cerebellar hemispheres = ipsilateral limb dysmetria, hypotonia, tremor; veer to the affected side on walking
Acute cerebellar ataxia - general
- Key points
a. Occurs in children 1-3 years of age
b. Diagnosis of exclusion; classically
i. Rapid onset of symptoms
ii. History of prodromal illness
iii. Absence of signs suggesting alternative diagnosis
c. Thought to represent an autoimmune response affecting the cerebellum - Clinical manifestations
a. Symptoms
i. Often follows a viral illness (eg. varicella, coxsackie) by 2-3 weeks
ii. Sudden onset truncal ataxia – child often unable to stand or sit
iii. Vomiting may occur initially – fever and nuchal rigidity absent
b. Signs
i. The gait is typically wide-based, unsteady, lurching, or staggering.
ii. Speech abnormalities such as fluctuations in clarity, rhythm/fluency, tone, and volume may occur.
iii. Posture while sitting unsupported may be difficult to maintain, with corrections and oscillations (titubation)
iv. Coordination and targeting of voluntary movements may be impaired, as seen on finger-nose testing (dysmetria) and during rapid alternating movements (dysdiadochokinesia).
v. Hypotonia, action tremor, and end-gaze nystagmus may also occur - Investigations
a. CSF = usually normal, may have pleocytosis
b. Brain imaging indicated if any atypical features - Natural history
a. Ataxia improves in a few weeks
b. May persist for as long as 3 month - Treatment
a. Supportive
b. Steroids and IVIG sometimes given - Prognosis
a. Resolves without sequelae usually within 2-3 weeks
Hereditary ataxias - list
Ataxia telangiectasia
Spinocerebellar ataxias
Friedreichs ataxia
Ataxia telangiectasia - background
Uptodate: Hereditary ataxia has a variety of causes. One cause is an autosomal recessive disorder associated with defective DNA repair mechanisms: ataxia-telangiectasia (AT; MIM 208900). Patients with AT develop progressive cerebellar ataxia, abnormal eye movements, other neurologic abnormalities, oculocutaneous telangiectasias, and immune deficiency.
- Key points
a. Most common degenerative ataxia - Genetics + pathogenesis
a. Autosomal recessive
b. Mutation 12q22.3 – ATM gene (AT mutated)
d. ATM is involved in detection of DNA damage and cell cycle progression
e. In the absence of the supervisory function of ATM, cells can build up somatic mutations, possibly leading to malignant transformation
f. Results in cerebellar atrophy
Ataxia telangiectasia - manifestations
a. Main features
i. Progressive cerebellar ataxia
1. Earliest clinical manifestation
2. Variable age of onset - <2 years
3. Unusually narrow base (cf. other causes of ataxia)
4. Loss of ambulation in adolescence
ii. Abnormal eye movements
1. Oculomotor apraxia of horizontal gaze (difficulty fixating smoothly on an object)
2. Strabismus
3. Nystagmus
iii. Neurological abnormalities
iv. Oculocutaneous telangiectasias
1. Occur by mid-childhood
2. Located on bulbar conjunctivae, bridge of nose and exposed surfaces
v. Immune deficiency
1. Cellular and humoral immunity
2. Decreased secretory IgA, diminished IgG2, Ig4 and IgE
b. Other features
i. Café au lait macules
ii. Pulmonary disease
1. Recurrent sinuopulmonary infections and bronchiectasis
2. Interstitial lung disease/ pulmonary fibrosis
3. Neuromuscular disease
iii. Malignancy
1. High risk of Lymphoreticular tumours + brain tumours
iv. Radiation sensitivity
v. Growth retardation
vi. Diabetes mellitus
Ataxia telangiectasia - diagnosis
Uptodate: Diagnostic criteria for ataxia-telangiectasia
Definitive diagnosis*
Male or female patient with either increased radiation-induced chromosomal breakage in cultured cells or progressive cerebellar ataxia and who has disabling mutations on both alleles of ATM.
Probable diagnosis*
Male or female patient with progressive cerebellar ataxia and three of the following four findings:
1. Ocular or facial telangiectasia.
2. Serum IgA at least 2 SD below normal for age.
3. Alpha fetoprotein at least 2 SD above normal for age.
4. Increased radiation-induced chromosomal breakage in cultured cells.
Possible diagnosis*
Male or female patient with progressive cerebellar ataxia and at least one of the following four findings:
1. Ocular or facial telangiectasia.
2. Serum IgA at least 2 SD below normal for age.
3. Alpha fetoprotein more than 2 SD above normal for age.
4. Increased chromosomal breakage after exposure to irradiation.
The diagnosis is established by identification of pathogenic variants on both alleles for the AT mutated gene (ATM). Another diagnostic method involves a rapid immunoblotting assay for ATM protein, which is severely depleted in most patients with AT. However, this procedure requires a large blood sample and is available in few laboratories.
Spinocerebellar ataxias - general
- Key points
a. Over 30 different types
b. Cerebellar ataxia a feature of each type
c. 60-70% of individuals have mutations - Genetics
a. Several types are associated with expansion of CAG repeats
d. Results in a toxic ‘gain of function’ protein
e. Greater number of alleles the earlier age of onset and more severe disease
f. Anticipation occurs - Clinical manifestations
a. Typically present in middle age with progressive ataxia, neuronal dysfunction + neuronal loss
Friedreich’s Ataxia - general
- Key points
a. Most common hereditary ataxia - Genetics + pathogenesis
a. AR
b. Tripe GAA report in gene encoding for the mitochondrial protein frataxin
c. Results in reduction in the production of frataxin protein
d. Size of repeat correlates with complications of disease
i. Normal <36
ii. Affected = 56-1300
e. Oxidative injury excessive iron deposits in mitochondria
f. Involves spinocerebellar tracts, dorsal columns in the spinal cord, pyramidal tracts - Natural history
a. Average onset 10-15 years (2 – 60
)
b. Average age at death 37 years - Clinical features
a. Ataxia
i. Onset 10 years of age
ii. Involves lower extremities > upper extremities
iii. Romberg +ve, absent tendon responses
iv. Posterior column dysfunction = marked loss of vibration and position sense
v. Upgoing plantars + loss of lower limb reflexes
b. Dysarthric speech
c. Nystagmus
d. Preserved intelligence
e. Skeletal malformations – eg pes cavus, hammertoes, kyphoscoliosis
f. Hypertrophic cardiomyopathy
g. Diabetes mellitis - Investigations
a. Genetic testing
b. Neuroimaging - Management
a. Antioxidant therapy with coenzyme Q10
b. Vitamin E
Idiopathic intracranial hypertension - background
- Key points
a. Clinical syndrome that mimics brain tumours and is characterised by:
i. Increased ICP = > 250 mmH2O in non-obese, non-sedated children with a normal CSF cell count and protein content
ii. Normal to slightly decrease ventricular size
iii. Normal CSF cell count and protein content
iv. Normal ventricular anatomy and position
b. Papilledema is universally present if child old enough to have a closed fontanelle - Risk factors
a. Recent weight gain
b. Medications - Aetiology (IDIOPATHIC, but associated with):
a. Haematological = Wiskott-Aldrich syndrome, polycythaemia, aplastic anaemia etc
b. Infections = acute sinusitis, otitis media etc
c. Drugs = tetracyclines, nalidixic acid, doxycycline, nitrofurantoin, isotretinoin, growth hormone etc.
d. Renal = nephrotic syndrome
e. Nutritional = hypovitaminosis A, vitamin A intoxication
f. CT disorders = antiphospholipid syndrome
g. Endocrine = menarche, PCOS, hypothyroidism
h. Other = dural venous sinus thrombosis, obesity, head trauma
i. Possible associations = CF, cystinosis, Down syndrome
Idiopathic intracranial HTN - manifestations/ix
Uptodate:
Symptoms
●Headache (84 to 92 percent)
●Transient visual obscurations (68 to 72 percent)
●Intracranial noises (pulsatile tinnitus; 52 to 60 percent)
●Photopsia (48 to 54 percent)
●Back pain (53 percent)
●Retrobulbar pain (44 percent)
●Diplopia (18 to 38 percent), typically from nonlocalizing sixth nerve palsy
●Sustained visual loss (26 to 32 percent)
●Neck pain (41 percent)
Examination — The most common signs in IIH are:
●Papilledema
●Visual field loss
●Sixth nerve palsy
- Clinical manifestations
a. History
i. Chronic (weeks to months), progressive, frontal headache – may worsen with postural change or Valsalva
ii. Vomiting – rarely as persistent and insidious as that associated with posterior fossa tumour
iii. Transient visual obscuration lasting seconds and diplopia (secondary to dysfunction of the CNVI nerve)
iv. Alert, lack constitutional symptoms
b. Examination
i. Infant – bulging fontanelle and ‘cracked pot sound’ (percussion results in resonant sound)
ii. Papilledema – with enlarged blind spot present in those with closed fontanelle
iii. Visual field loss – with enlarged blind spot present in those with closed fontanelle - Typically peripheral visual field loss
- Central visual field loss late in the course
iv. Visual acuity loss – occurs AFTER visual field loss
v. CNVI palsy
vi. Focal neurology prompt Ix to uncover process other than pseudotumour cerebri - Investigations
Uptodate: MRI, LP, ophthal exam
Idiopathic intracranial HTN - rx/prognosis
- Treatment
The treatment of IIH has two major goals: the alleviation of symptoms (usually headache) and the preservation of vision.
a. Treat underlying cause
i. Weight loss regimen = if obese
ii. If drug associated = discontinue offending drug
iii. Sinus thrombosis – anticoagulation
b. LP = initial LP that follows CT or MRI which is diagnostic is often therapeutic
i. Several additional LP and the removal of sufficient CSF to reduce the opening pressure by 50% occasionally leads to effective resolution
c. Medications
i. Carbonic anhydrase inhibitor: Acetazolamide 10-30 mg/kg/24 hour – effective
ii. Corticosteroids – not routinely given, however may be used if severe ICP elevation who is at risk of losing visual function and is awaiting decompression
d. Surgery = rarely VP shunt or sub-temporal decompression necessary
e. Surveillance
i. Serial monitoring of visual function – acuity, colour vision, visual fields
ii. Serial optic nerve examination
iii. Serial visual-evoked potentials – useful if visual acuity cannot be reliably documented - Prognosis
a. Can be a self-limited treatment, however optic atrophy and blindness are the most significant complications if left untreated
CNS vasculitis - background
- Definition: Childhood primary angiitis of the CNS (cPACNS) =
a. Newly acquired focal and or diffuse neurological deficits and/or psychiatric symptoms in a child
b. Angiographic and or histological evidence of vasculitis, in the absence of
c. Systemic underlying condition known to mimic findings - Classification
a. Primary CNS vasculitis
i. Large/medium vessels = diagnosed on angiography - Monophasic
- Non-progressive (NPcPACNS)
- Progressive (PcPACNs)
ii. Small vessel (SVcPACNS) = angiography negative + brain biopsy positive - Progressive illness
b. Secondary CNS vasculitis
- infectious (viral, bacterial, fungal, parasitic)
- systemic vasculitidies
- connective tissue disease
- drug induced, other inflammatory conditions
c. Autoimmune encephalitis
i. Intracellular Ag
ii. Receptor/cell surface Ag
CNS vasculitis - workup
a. Clinical evaluation = newly acquired symptoms or deficit in previously healthy child
i. Focal neurological deficit
ii. Seizures or refractory seizure status
iii. Diffuse neurological deficit including cognitive decline with loss of higher exectuve function, concentration difficulties, learning/memory problems, behavior or personality changes, loss of social skills
iv. Headaches
v. Meningitis symptoms, abnormal level of consciousness
vi. Pyschiatric symptoms including hallucinations, pseudoseizures
vii. DDx – underlying illness known to cause or mimic CNS vasculitis
b. Laboratory tests
i. Inflammatory markers (CRP, ESR, FBE)
ii. Endothelial markers = vWF antigen proposed biomarker of vasculitis correlating closely with disease activity in cPACNS
iii. CSF inflammatory markers and opening pressure
iv. DDx
1. Infections/post infectious inflammation – cultures, serology
2. Autoimmune encephalitis – check neuronal antibodies in CSF and blood
3. Systemic inflammation/rheumatic disease – characteristic laboratory markers such as complement, autoantibodies
4. Thromboembolic conditions – procoagulant profile
c. Imaging
i. Parenchymal imaging on MRI
1. Inflammatory lesions = T2/FLAIR sequence plus gadolinium (contrast enhancement)
2. Ischaemic lesions = diffuse weighted
ii. Vessel imaging
d. Brain biopsy
Small vessel (SvCPACNs):
Gender: Girls of all ages
Hallmark feature: Seizures
Inflammatory markers: Majority mildly raised
CSF: Abnormal in 90%
Oligoclonal bands: 20%
Neuroimaging: MRI lesions in children with SVcPACNs are not restricted to any territories; lesions are primarily inflammatory and may enhance with contrast
Vessel wall imaging often normal in SVcPACNs
Brain biopsy: Often required - Characteristic findings include intramural and/or perivascular mononuclear infiltrate, evidence of endothelial activation, and reactive astrocyte formation
Medium/large vessel cPACNs Gender: Male Hallmark feature: Stroke like features Inflammatory markers: >50% have normal inflammatory markers at presentation CSF: Abnormal in <50% Oligoclonal bands: - Neuroimaging: Evidence of vessel stenosis on angiography confirms large/medium cPACNs Brain biopsy: Not required
CNS vasculitis - rx/prognosis
- Treatment
a. Two aspects
i. Corticosteroids = the mainstay of treatment – IV pulse therapy usually given initially
ii. Antithrombotic therapy = particularly important for large/medium vessel cPACNs as high risk for recurrent events
b. Non-progressive cPACNs = monophasic inflammatory attack with the highest risk of poor outcome
i. Vessel wall inflammation causes several proximal stenoses and a high re-stroke risk
ii. High dose corticosteroids
iii. Second line immunosuppressives often given
iv. Antithrombotic therapy essential
c. Progressive cPACNs and SVcPACNs = considered chronic vasculitis
i. Long-term immunosuppression = high dose corticosteroids taper; other agents (eg. cyclophosphamide, mycophenolate) also used - Prognosis
a. Mortality for cPANS has significantly improved
b. Children presenting with status epilepticus and SVcPANS have the poorest prognosis
Encephalopathies - aetiology
HIV Lead Burns (5%, no cause identified, supportive) Hypertensive Radiation Acute necrotising Autoimmune Demyelinating (ADEM)
Hypertensive encephalopathy - general
a. Commonly associated with renal disease in children
b. Can sometimes be the initial manifestation of renal disease
c. Pathogenesis = marked systemic HTN produces vasoconstriction of cerebral vessels areas of focal edema and haemorrhage
d. Clinical features
i. Onset can be acute – seizures, coma
ii. Or more indolent onset – headache drowsiness and lethargy, nausea and vomiting, blurred vision, transient cortical blindness and hemiparesis
iii. Examination may show papilledema and retinal hemorrhage
e. Posterior reversible leukoencephalopathy syndrome (PRES) = MRI shows increased signal intensity in the occipital lobe on T2 weighted images
i. Can be seen in children without hypertension
ii. In all circumstances manifests with generalised motor seizures, headache, mental state changes, visual disturbances
Radiation encephalopathy - general
a. More likely in young patients who receive large daily doses
b. Acute
i. Pathogenesis = excessive injury damages endothelium enhanced vascular permeability, cerebral edema and hemorrhages
ii. Clinical features = Irritability and lethargy, c/o headache, focal neuro signs and symptoms or seizures
iii. Treatment = steroids are often helpful in reducing cerebral edema
c. Late
i. Characterised by headaches and slowly progressive neurologic signs including hemiparesis and seizures
ii. Exposure of the brain to radiation for treatment of childhood cancer increases the risk of later CV disease – stroke, Moyamoya disease, aneurysm, vascular malformation, mineralizing microangiopathy, stroke-like migraines
iii. Some children with ALL treated with intrathecal MTX develop neurologic signs months or years later
Acute necrotising encephalopathy - general
a. Rare, severe encephalopathy
b. More common in Asian countries
c. Triggered by viral infection – HHV6, influenza
d. Genetically susceptible host
e. Elevation of hepatic enzymes WITHOUT hyperammonaemia is a unique feature
f. Familial recurrent form associated with mutations in RANBP2 gene
g. MRI findings are characterised by symmetric lesions in the thalami
h. Prognosis is poor
i. Treated with steroids + IVIG
Autoimmune encephalitis - background
- Background/Overview
a. Encephalitis = inflammation of the brain parenchyma
b. Classification = infectious vs autoimmune
c. Autoimmune encephalitis should be suspected in any persons who present with an acute encephalopathy with behavioural change, seizures, dystonia or dyskinesia
d. Clinical manifestation = encephalopathy with persistent ACS, fever, seizures and/or focal neurological deficits
e. Early recognition and treatment with immunotherapy shortens illness duration and improves outcome - Pathogenesis
a. Autoimmune encephalitides = pathogenic autoantibodies target synaptic or cell-surface proteins expressed on neurons within the CNS, disrupting neurotransmission leading to the clinical features observed
b. Described syndromes of autoimmune encephalitis have been associated with autoantibodies against:
i. N-Methyl-D-Aspartate receptor (NMDAR)
ii. Voltage-gated-potassium-channel complex (VGKC), which includes: - Leucine-rich glioma inactivated 1(LGI1)
- Contactin associated protein 2 (CASPR2)
iii. Glycine receptor (GlyR)
iv. Glutamic acid decarboxylase (GAD)
v. AMPA receptor (AMPAR subunits GluR1/2)
vi. GABA type B receptor (GABABR1) - DDx
a. Infection = HSV, VZV, Enterovirus, Mycoplasma pneumoniae, Influenza, EBV, CMV, HHV6, Japanese B encephalitis
b. Demyelination = acute disseminated encephalomyelitis
c. Rheumatic/post-streptococcal movement disorder (Sydenham’s chorea)
d. Neurologic manifestations of systemic lupus erythematosus
e. Hashimoto’s encephalopathy (rare)
f. Cerebrovascular event (thromboembolic, haemorrhagic or vasculitic)
g. Intracerebral mass/structural lesion
Autoimmune encephalitis - manifestations (RCH guideline)
- Principles of diagnosis
a. Phenotypic features allow clinical suspicion but are not sensitive or specific
b. Detection of the autoantibody in serum or in CSF confirms diagnosis – CSF more sensitive - History and examination
a. Important aspects of history
i. Tempo and onset of symptoms
ii. Behavioural change - Younger children: tantrums, irritability, agitation
- Older children (>12): hallucinations, bizarre behaviour, acute psychosis
iii. Abnormal movements noted by parents/carers - Dystonic posturing
- Involuntary movements
a. Can persist through sleep
b. Can affect face (eg orolingual dyskinesia) or peripheries
c. Can be unilateral or bilateral
iv. Seizures = temporal lobe (HSV or limbic encephalitis), focal, generalised
v. Sleep disturbance = insomnia or hypersomnolence
vi. Speech or language difficulties
vii. Prodrome = fever, headache, N+V, diarrhoea, upper respiratory symptoms in the preceding 1-2 weeks
viii. Toxins exposure
ix. Immunodeficiency = at risk for infections including HSV, CMV, EBV, HHV6
b. Important aspects of examination
i. Mental state and signs of encephalopathy
ii. Movement disorder and dystonic posturing
1. Involuntary movements at rest and during activity
2. Apparent extensor plantar response without fanning of the toes (‘Striatal toe’)
iii. Language, speech and communication
1. Decreased spontaneous speech, perseverating speech
iv. Vital signs (Heart rate, blood pressure, respiratory rate)
v. Focal neurological deficits
vi. The presence of pyramidal signs (voluntary movement
Autoimmune encephalitis - ix
a. Bloods/other
i. Basic bloods: FBE, UEC, CMP, LFT, CRP, ESR, coagulation profile
ii. Serum oligoclonal bands (paired with CSF oligoclonal bands)
iii. Antibodies
1. Anti-NMDAR antibodies and anti-voltage-gated-potassium-channel (VGKC) antibodies
2. Anti-neuronal antibodies
3. ANA
4. Streptococcal serology (ASOT and Anti-DNase B) (follow-up serology required)
5. Other autoantibodies associated with encephalitis:
a. anti-GAD Ab, anti-GlyR Ab, anti-AMPAR Ab, Anti-GABABR1 Ab
b. Anti-dsDNA, anti-cardiolipin antibody (if ANA positive and lupus suspected).
c. Anti-thyroid antibodies, anti-thyroglobulin antibodies, TSH
iv. Ammonia, lactate, pyruvate
v. Store serum
b. Neuroimaging
i. Imaging (MRI-brain) should be performed in ALL CHILDREN to exclude differential diagnoses
ii. MRI-brain is non-diagnostic in 50-80%
c. LP
i. Lymphocytic pleocytosis and increased protein is usually seen
ii. Also test for:
1. Oligoclonal bands
2. PCR: HSV, Enterovirus, Mycoplasma pneumoniae and others as clinically appropriate.
3. CSF autoantibody assay may be required, particularly if autoantibody not detected in serum
d. EEG
i. Should be performed if clinically encephalopathy or if seizures present
ii. May have no abnormalities at onset, progressing to widespread ictal and interictal epileptiform activity in the early stages generalised diffuse, dysrhythmic, high amplitude slowing with no clinical correlate
iii. An extreme delta brush pattern has been associated with this disorder
e. Other = pelvic and abdominal ultrasound = for girls if anti-NMDAR antibodies detected, to exclude presence of an ovarian teratoma (infrequently associated)
Autoimmune encephalitis - rx/prognosis
- Treatment
a. Specific treatments
i. Treatment for infectious encephalitis until proven otherwise (IV antibiotics and antivirals)
ii. Immunotherapy once diagnosis confirmed or strongly suspected: - IVIG 1 g/kg/day for two days, AND
- IV Methylprednisolone 30mg/kg/day (maximum 1g/day) for five days oral pred taper (3 mo)
- If no response after 10 days, consider:
a. IV Rituximab 375mg/m2 (round off to nearest 100mg) weekly for four weeks
b. Cyclophosphamide or another immune-modulatory treatment may be considered.
iii. Removal of ovarian teratoma if present (within 4 months of presentation)
iv. Anticonvulsants should be commenced to manage recurrent seizures
v. Sleep disturbance and agitation can be managed by use of melatonin or chloral hydrate
vi. Small doses of benzodiazepines and chloral hydrate can be considered for periods of extreme agitation, with consideration of risperidone if ineffective
b. General measures
i. Behavioural and environmental modification to minimise agitation.
ii. Consultation-liaison psychiatry may be involved for management of psychiatric features.
iii. Monitor oral intake and nutrition.
iv. Appropriate involvement of allied health and rehabilitation specialists.
v. Physiotherapy, occupational therapy, speech therapy, social work
- Outcome
a. Improvement can be slow, over months, but complete recovery can occur
b. Children should have regular follow up and tumour surveillance annually for 2 years
i. Small risk of relapse in 15-20%.
ii. Abdominal/pelvic imaging should be considered if there are features of relapse.
Anti-NMDA encephalitis - background
a. Pathogenies
i. IgG antibodies bind to the NR1 (or less commonly NR2) subunit of NMDAR, prompting the receptors to be internalised into the neuron
ii. As neurotransmitters glutamate and glycine can no longer bind to the receptor, the GABAergic neurons are functionally inactivated and excitatory pathways are disinhibited
b. Epidemiology
i. Most common autoimmune encephalitis affecting both adults and children
ii. Considered 2nd most common cause of encephalitis after ADEM
iii. Predominates in females (80%) and those >12 years (although in patients <12 years males more common)
f. Cause
i. Teratoma association
1. 40% of females >12 year have underlying teratoma of ovary (6% of children <12 years)
2. In boys the presence of underlying tumour exceptional
3. MRI abdomen + USS = to screen for teratoma
ii. Infections
1. In a small number of patients occurs simultaneously or after infections with a variety of pathogens, including Mycoplasma pneumoniae, HSV, enterovirus and influenza
Anti-NMDA encephalitis - manifestations
c. Clinical presentation – based on phase:
i. Prodrome in 50%
ii. Early phase
1. Frontostriatal features (psychosis, behavioural change, short term memory impairment)
2. Movement disorder (hyperkinetic choreoathetosis or catatonia)
3. Dystonia
4. Seizures
5. Sleep disturbance
iii. Late phase
1. Language disintegration (echolalia, mutism)
2. Autonomic instability
3. Breathing dysfunction, hypoventilation
4. Enuresis, urinary incontinence
5. Episodes of tachycardia, hyperthermia, hypertension
d. Clinical presentation – based on age:
i. Teenagers and young adults
1. Prominent psychiatric manifestations that may include rapidly progressive anxiety, agitation, delusional thoughts, bizarre behavior, labile affect, mood disturbances (mania), catatonic features, memory deficit, language disintegration, aggression, catatonic features, sleep disturbance
2. May be preceded by a few days of prodromal headache, fever or viral like symptoms
3. Can be mis-diagnosed as new onset psychiatric disorder
4. Further symptoms – decreased LOC, seizures (including status), limb or oral dyskinias, choreoathetoid movements, and autonomic instability (tachy, brady, BP fluctuation, hypoventilation, hypertherimia, and Sialorrhoea)
ii. Toddlers and infants
1. Motor or complex seizures and movement disorder
2. Psychiatric behavioural features may be missed – may have temper tantrum, agitation, aggression, reduced speech, mutism, autistic-like regression
3. Cerebellar ataxia and hemiparesis
4. Autonomic dysfunction milder and less frequent
Anti-NMDA encephalitis - ix/rx/prognosis
e. Investigations
i. MRI-B = abnormal in 35% of cases
ii. CSF = abnormal in 80%; moderate lymphocytic pleocytosis, less frequently increased protein synthesis and oligoclonal bands
iii. EEG = abnormal in all patients, focal or diffuse slowing, characteristic ‘extreme delta brush’
iv. NDMA receptor Ab present in CSF or serum – sensitivity higher in CSF compared with serum (100% vs 85%); level of autoantibodies in the CSF correlate to outcome – may remain detectable after the patient recovers
g. Treatment
i. Teratoma removal
ii. Corticosteroids IVIG, plasma exchange
iii. Rituximab – increasingly being used
iv. Cyclophosphamide – has also been used
h. Prognosis
i. Mortality rate 7%
ii. Full or substantial recovery in 75-80%
1. Slow recovery, can take as long as 2 years
2. Last symptoms to improve are social interactions, and language and executive function
3. Relapse occurs in 15-25% of patients – respond to immunotherapy
Hashimotos encephalitis
a. Defined by the detection of thyroid peroxidase (TPO) Ab in patients with acute or subacute encephalitis that responds to corticosteroids
b. 50% have normal thyroid function
c. Clinical features = stroke-like symptoms, tremor, myoclonus, transient aphasia, sleep and behavioral abnormalities, hallucinations, seizures, ataxia
d. Investigations
i. CSF = elevated protein, less frequent pleocytosis
ii. EEG = abnormal with generalised slowing
iii. MRI =usually normal
iv. TPO antibodies can occur in asymptomatic children
Opsoclonus myoclonus encephalitidies - general
a. Occurs in infants, teenagers and adults
b. Infants
i. Develops in the first 2 years of life (mean 20 months)
ii. 50% have neuroblastoma
iii. Clinical presentation = irritability, ataxia, falling, myoclonus, tremor and drooling
iv. Additional symptoms = refusal to walk or sit, speech problems, hypotonia, typical features of opsoclonus (rapid, chaotic, multidirectional eye movement without saccadic intervals)
v. May be diagnosed as acute cerebellitis
vi. CSF = B cell activation and antibodies against neuronal Ag
vii. Treatment = immunosuppressive (corticosteroids, IVIG, rituximab, cyclophosphamide)
viii. Prognosis
1. Eye movements improve with immunosuppression
2. Residual behavioral, language and cognitive problems
3. Relapse occurs in 50% of patients due to intercurrent infection or drug tapering
4. Removal of tumour should NOT delay immunosuppression
c. Teenagers and young adults
i. Often considered idiopathic or post-infectious
ii. Some patients do have underlying teratoma
iii. CSF = pleocytosis and elevated protein
iv. Treatment = immunosuppression
v. Prognosis = patients usually have a full recovery and if present, removal of teratoma
1. Better prognosis than neuroblastoma associated opsoclonus, OR the paraneoplastic opsoclonus of older patients related to breast, ovarian or lung cancer
Rasmussen encephalitis
i. Inflammatory encephalopathy characterised by progressive refractory partial seizures, cognitive deterioration and focal deficits that occur with gradual atrophy
ii. Frequently presents in 6-8 year old children, although adolescents and adults can be affected
iii. Etiology unknown
iv. Treatment = high dose steroids, IVIG, rituximab
v. Only definitive treatment is functional hemispherectomy
Rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHADD)
i. Affects children who had normal development until 2-4 years of age
ii. Develop Hyperphagia, weight gain, abnormal behavior, lethargy, outburst of euphoria and laughing, impaired concentration autonomic dysfunction (abnormal pupillary responses, thermal dysregulation, GI dysmotility) and central hypoventilation
iii. Cause unknown
Tethered Cord - general
- Key points
a. Beyond infancy the spinal cord ends at the level of L1
b. The position of the conus BELOW L2 is consistent with a congenital tethered spinal cord
c. If the spinal cord is fixed at any point the normal movement is restricted stretching of nerve roots
i. Usually caused from a thickened filum terminale which attaches to the sacrococcygeal region
ii. Can also result from occult spinal dysraphism (eg. lipomyelomeningocele, myelocystocele, and diastematomyelia)
d. Tethered cord syndrome = severe pain or neurological deterioration associated with fixation - Clinical manifestations
a. Occult spinal dysraphism
b. Asymmetry of feet – smaller foot has a high arch and clawing of toes, no ankle jerk, atrophic calf (neuro-orthopedic syndrome)
c. Acute deterioration manifested by urinary urgency, incontinence, deterioration in motor and sensory function, severe back pain - Investigations = MRI
- Treatment = neurosurgery
- Outcome = generally good outcome
Diastematomyelia - general
- Key points
a. Rare form of occult spinal dysraphism – spinal cord is divided into 2 halves
b. Type 1 = 2 spinal cords each with its own dural tube and separated by a spicule of bone and cartilage
c. Type 2 = 2 spinal cords are enclosed in a single dural sac with a fibrous septum - Clinical manifestations
a. May have subtle signs of neurological involvement – unilateral calf atrophy and a high arch to 1 or both feet
b. Manifestations of tethered spinal cord
c. May develop loss of bladder and bowel function, sensory and motor difficulties
d. Back pain is common
e. Cutaneous manifestations of dysraphism present in 90% - large, hairy, midline patch most common - Investigation = MRI
- Treatment = neurosurgical
Syringomyelia - general
- Key points
a. Cystic distension of the spinal cord caused by obstruction of the flow of spinal fluid from within the spinal cord
b. Classification
i. Communicating syringomyelia = ventricular CSF communicates with the fluid within the spinal cord
ii. Non-communicating syringomyelia = ventricular CSF does not communicate with the fluid within the spinal cord; occurs in the context of intramedullary tumours and obstructive lesions
iii. Post-traumatic syringomyelia = injury followed by softening of the spinal cord
c. Associated with Chiari anomalies in patients with EDS - Clinical manifestations
a. Insidious onset
b. Central cord syndrome: Damage to the central spinal cord and the orientation of spinal tracts from proximal to distal leading to selective involvement of upper rather than lower limb
i. Numbness beginning in the shoulder in a cape-like distribution
ii. Followed by atrophy and weakness of the upper extremities – with trophic ulcers of the hands in advanced cases
c. Scoliosis = rapidly progressive
d. Urgency and bladder dysfunction - Investigations = MRI
- Treatment
a. Determined by the underlying cause
Spinal Cord Tumour - general
- Key points
a. Rare in children - Classification
a. Intra-medullary
i. Arise within the spinal cord itself
ii. 10% are malignant astrocytic tumours
iii. Most are grade I or II tumours of glial or ependymal origin
iv. Ependymomas in children are frequently associated with NF-2
b. Extra-medullary
i. Intra-dural - Occur in NF-1 and NF-2
- Most are nerve sheath tumours – schwannomas (NF1) or neurofibromas (NF2)
- Intraspinal meningiomas are only found in patients with NF2
ii. Extradural - Primary tumour
a. Aneurysmal bone cyst
b. Langerhans cell histiocytosis
c. Giant cell tumours - In infants – neuroblastoma or ganglioneuroblastoma
- Clinical manifestations
a. Dependent on site and obstruction of CSF
CSF production
a. CSF is produced by the choroid plexus – present in lateral, 3rd + 4th ventricles
i. Most comes from the lateral ventricles
ii. 25% comes from extrachoroidal sources – eg capillary endothelium within brain parenchyma
b. Production regulated by nervous system
i. Adrenergic system stimulation CSF production diminishes
ii. Cholinergic system stimulation increases CSF production
c. Normal pattern of flow
i. Lateral ventricles
ii. Through the foramen of Munro into the 3rd ventricle
iii. Then goes via aqueduct of Silvius (very narrow) into 4th ventricle
iv. Exits from 4th ventricle through paired lateral foramina and midline foramen into basal cisterns
d. Reabsorption
i. Primarily resorbed via arachnoid villi
ii. To a lesser extent by lymphatic channels + choroid plexus
Hydrocephalus - general
Hydrocephalus is a disorder in which an excessive amount of cerebrospinal fluid (CSF) accumulates within the cerebral ventricles and/or subarachnoid spaces, resulting in ventricular dilation and increased intracranial pressure (ICP).
- Aetiology + Classification
a. Obstructive = non-communicating
i. Narrowed aqueduct of sylvius – has some rare associations - May be sex linked recessive trait
- May be associated with neurofibromatosis
- Occasionally have minor neural tube defects
ii. Aqueductal gliosis
iii. Neonatal meningitis (interrupted ependymal lining gliosis which obstructs)
iv. Intrauterine viral infection
v. Vein of Galen malformation
vi. Posterior fossa lesions (brain tumours, Chiari malformation, Dandy-Walker syndrome)
b. Non-obstructive = communicating (obliteration of cisterns/ arachnoid villi)
i. Subarachnoid haemorrhage
ii. Pneumococcal/ tuberculous meningitis (may produce exudate that obstructs basal cisterns) - Clinical manifestations
a. Infants
i. Enlarged head
ii. Open, bulging anterior fontanelle
iii. Dilatation of scalp veins
iv. Sunsetting eyes – due to impingement of dilated suprapineal recess on the tectum (midbrain)
v. Disruption of corticospinal tracts -> brisk tendon reflexes, spasticity, clonus
b. Older children
i. Headache, irritability, lethargy
Headaches - background
- Classification
a. Primary headaches
i. Migraine
ii. Tension type headaches
iii. Trigeminal autonomic cephalgias
b. Secondary
i. Sinus
ii. Raised ICP - Headache red flags
a. Acute and severe
b. Progressive chronic
c. Focal neurology
d. Age < 3 years
e. Headache/vomiting on waking
f. Consistent location
g. Unusual location/pattern
h. Presence of VP shunt
i. Hypertension - Consider intracranial imaging in
a. Abnormal neurology
b. Meningism (consider LP)
c. Marked changes in behaviour
d. Symptoms of raised intracranial pressure
e. Increasing frequency of undiagnosed headaches
f. Onset of severe headache - Recurrent headaches
a. Tension type (~50% incidence)
i. Non-pulsatile band
ii. Often end of day
iii. Few associated symptoms
b. Migraines (~25%):
i. Pulsing pain
ii. Nausea
iii. Photophobia
iv. Phonophonia
v. Often unilateral - Red flags
a. ‘Unusual headaches’
i. Occipital
ii. Atypical auras
iii. Trigeminal autonomic cephalgia
b. Abnormal/ focal signs or symptoms
c. Seizures or very brief auras
d. Early morning vomiting
e. Migraine present on waiting
f. Change with posture / occur with cough/ bending over
g. Migraines without a family history
Migraine - background
- Epidemiology
a. 10.6% of children between 5-15, 28% of older adolescents
b. Without aura more common in children
c. 90% have family history - Differences in children
a. May be shorter (1-72 hors)
b. If child falls asleep, this sleep period is considered part of the duration
c. More commonly bilateral
d. Nausea and vomiting may be more prominent, associated with:
i. Recurrent abdominal pain
ii. Cyclic vomiting
iii. Abdominal migraine
iv. Note – children with these syndromes have a propensity to develop migraine
Migraine - diagnosis
- Diagnostic criteria
a. Migraine without aura
i. At least 5 attacks
ii. Headaches lasting 4-72 hours (untreated or unsuccessfully treated)
iii. Headaches with at least 2 characteristics – unilateral, pulsating, moderate-severe, aggravated by or causing avoidance of physical activity
iv. During the headache at least 2 of
1. Nausea and/or vomiting
2. Photophobia or phonophobia
v. Not attributed to another disorder
b. Migraine with aura, typical
i. At least 2 attacks
ii. Aura consists of at least 1 of the following, but no motor weakness
1. Fully reversible visual symptoms
2. Fully reversible sensory symptoms
3. Fully reversible dysphasic speech disturbance
iii. At least 2 of the following
1. Homonymous visual symptoms and/or unilateral sensory symptoms
2. At least 1 aura symptom develops gradually over >=5 minutes and/or different aura symptoms occur in succession over >= 5 minutes
3. Each symptom lasts >=5 and <=60 minutes
iv. Headache as for migraine without aura – begins during aura or follows within 60 minutes
v. Not attributed to another disorder
- Other clinical features:
a. Photophobia/ phonophobia may develop as the child ages
b. Triggers may be present – skipping meals, dehydration, weather change
c. Aura
i. Typically lasts 5-60 minutes
ii. Occurs within 60 minutes of headache starting
iii. Most common aura in children is photopsia (flashes of light)
iv. Sensory, dysphasic and atypical (hemiplegia/ vertical/ cranial nerve symptoms and distortion) symptoms are less common
Migraine - types
a. Hemiplegic migraine
i. Rare form of aura; transient unilateral weakness lasting for few hours-days
ii. Associated with at least 3 identified genes
b. Basilar type migraine
i. Associated with vertigo, tinnitus, diplopia, blurred vision, scotoma (blind spot), ataxia and occipital headache
ii. Pupillary dilatation and ptosis
c. HaNDL ‘pseudomigraine’ – transient headache with neurologic deficits + CSF pleocytosis
d. Childhood periodic syndromes
i. Recurrent GI symptoms, sleep disorders
ii. May be treated with migraine therapies
Migraine - ix/rx
- Investigations
a. MRI = best sensitivity for posterior fossa lesions - Management
a. Acute
i. Supportive = hydration, dark room
ii. Pharmacological = most effective if given earlier
1. NSAIDs = ibuprofen, naproxen, aspirin (older children)
2. Triptans (if >12 years)
3. Chlorpromazine 0.15 mg/kg IV in 1L normal saline
a. Monitor for hypotension
4. Anti-emetics
b. Preventative
i. Indicated for frequency (> 1 / week) or disabling symptoms
ii. Other indications
1. Frequent or long lasting migraine headaches
2. Migraine attacks that cause significant disability or diminished quality of life despite appropriate acute treatment
3. Contraindication to acute therapies
4. Failure of acute therapies
5. Serious adverse effects of acute therapies
6. Risk of medication overuse headache
7. Menstrual migraine
iii. Aim is to reduce frequency to < 2 / month
iv. Give prophylactic medications for at least 4-6 months then wean:
- Flunarizine – only agent proven to be effective in trials
a. Calcium channel blocker - Beta blockers
a. Propranolol = the most common choice
b. Contraindicated – asthma/ allergy/ depression , particularly effective in basilar type migraine with POTS - Cyproheptadine
a. Antihistamine and serotonin antagonist with anticholinergic and calcium channel blocking properties
b. Often used in young children who cannot take tablets – syrup - Amitriptyline
- Anti-epileptics – few studies in children, Topiramate + valproate in adults
v. Biofeedback therapy has been shown to be effective
Tension Type Headaches - general
50% of recurrent headaches
- Clinical manifestations
a. Mild to moderate in nature
b. Diffuse in location “non-pulsatile band”
c. Not affected by activity, often at the end of the day
d. Tend to be ‘constant pressure’, less associated with nausea/photophobia/phonophobia
e. CAN be recurrent – needs at least ten, lasting 30 minutes – 7 days - Management
a. Acute
i. Paracetamol
ii. Nurofen
b. Prevention
i. Amitriptyline
ii. Biobehavioural intervention
Ptosis - differentials
Congenital abnormality of the levator muscle
- Levator function: Reduced
- Eyelid crease margin: Crease often absent
- Often unilateral
- Many patients also have amblyopia, strabismus
Aponeurotic ptosis
- Levator function: Normal
- Eyelid crease margin: Often increased
- Uni- or bilateral
- Isolated finding of ptosis
Cranial nerve 3 palsy
- Levator function: Reduced
- Eyelid creases: Normal
- Usually unilateral
- Impaired extraocular movement in ipsilateral eye
- If ipsilateral pupil dilated, urgent evaluation for aneurysm is required.
Horner’s syndrome
- Levator function: Normal
- Eyelid creases: Normal
- Usually unilateral
- Ipsilateral miotic pupil
Myasthenia
- Levator function: Reduced
- Eyelid creases: Normal
- Uni- or bilateral
- Variable and fatigable
- Diplopia and extraocular movement abnormalities often present
Muscle disease
- Levator function: Reduced
- Eyelid creases: Normal
- Usually bilateral
- Orbicularis oculi, other extraocular or bulbar muscles may be affected
Congenital Ptosis
• Most often associated with absence or reduction of striated levator palpebrae superioris muscle
• Unilateral (75%), neurologically and non-progressive
• Can have a familial association – autosomal dominant trait
BPPV - general
- Key points
a. Benign paroxysmal (positional) vertigo (BPV) is a disorder of early childhood manifested by recurrent episodes of brief disequilibrium
b. A family history of migraine headaches is frequently present
c. The neurologic examination is normal between episodes - Clinical manifestations
a. During the attacks, the child appears frightened and off balance, often reaching out to steady him or herself
b. The events may be associated with nystagmus, diaphoresis, nausea, and vomiting
c. Older children will grab nearby persons or furniture for support to prevent falling and may complain of vertigo or dizziness
d. Episodes usually last less than a minute and are not associated with an altered consciousness
e. They usually recur in clusters, occurring daily for several days in a row, then remitting for several weeks, and recurring again - Natural history
a. The disorder typically remits spontaneously by five years of age
b. Many patients subsequently develop typical migraine headaches
Telencephalon
Embryologic structure that becomes the cerebral hemispheres, gyri and sulci
Diencephalon
Embryologic structure that becomes the thalamus and hypothalamus
Mesencephalon
Becomes the midbrain
Metencephalon
Becomes the cerebellum and pons
Myeloncephalon
Becomes the medulla
Brain lobes - function and impairment
FRONTAL LOBE Function • Planning, executive function, inhibition • Precentral gyrus: motor cortex • Broca’s area (expressive speech) Impairment • Primitive reflexes • Anosmia • Gait apraxia • Dysphasia (expressive)
PARIETAL LOBE Function • Postcentral gyrus: sensory cortex • Secondary sensory cortices • Speech = fluent, amnestic nominal Impairment • Dysphasia • Acalculia, agraphia, left right disorientation , finger agnosia • Neglect , inattention
TEMPORAL LOBE Function • Auditory processing • Wernicke’s area (posterior temporal) • Semantic memory • Relationship to the hippocampus Impairment • Memory loss
OCCIPITAL LOBE Function • Vision Impairment • Homonymous hemianopia
CEREBELLUM Function • Coordination Impairment • Ataxia • Nystagmus • Dysdiadokinesis
Subcortical structures - function and impairment
HYPOTHALAMUS
Function
• Connects with the midbrain, limbic system (via anterior and medial temporal cortex) and autonomic nuclei
• ‘Regulator’ hormones
Impairment
• Imbalances in temperature, sleep, salt/ water
THALAMUS (Bunch of nuclei: Latera geniculate nuclei, Medial geniculate nuclei, Ventral anterior nucleus, Ventral lateral nucleus)
Function
• Largest part of the diencephalon
• Projects to the cortex: receives input from basal ganglia -> motor cortex
• Connect limbic areas of the cerebral cortex
Impairment
• Mixed
• Loss of sensation in contralateral face and limbs
BASAL GANGLIA Function • Corpus striatum, substantia nigra (pars compacta and par reticularis), putamen, caudate nucleus • Output: medial globus pallidus, substantia nigra pars reticularis • Posture and movement Input zone Impairment • Choreathetosis • Dystonia, parkinsonism
PINEAL GLAND
Function
• Melatonin
• Onset of puberty
Internal capsule
Sheet of nerve fibres that extend between the cerebral cortex and subcortical stages
Diencephalic syndrome - general
Cause: Tumour in the hypothalamic optic chiasmatic region (low grade glioma or astrocytoma)
Features:
- FTT, severe emaciation
- Normal or increase caloric intake
- Locomotor hyperactivity and euphoria
- May have optic atrophy, nystagmus, tremor
Parinaud syndrome - general
Cause: pineal tumour
Features:
- vertical gaze nystagmus
- pupils constrict poorly to light but react to examination
Cranial nerves - general background
- Key points
a. Supply somatic and visceral motor and sensory information to head
i. CNIX and X also supply visceral sensory and motor innervation to neck, chest and most abdominal organs
b. Each cranial nerve is associated with a specific function or set of functions
c. 12 pairs of cranial nerves listed I-XII - Anatomy
a. Cranial nerve nuclei associated with brainstem are cranial nerves III to XII (I and II are not in brainstem)
b. Exit brainstem in order (rostro-caudal)
i. Most exit ventral surface except IV - Function
a. Motor
i. CNIII, IV, VI – control eye movements
ii. CNXI, XII
b. Sensory
i. CNI, II, VIII
c. Mixed
i. CNV, VII, IX, X - Rule of 4
a. 4 cranial nerves exit medulla = CNIX, X, XI, XII
b. 4 cranial nerves next the pons = CNV, VI, VII, VIII
c. 4 exit above the pons = CNI [not in midbrain], II [not in midbrain], III, IV
Cranial nerves - general function summary
CNI
- olfactory
- sensory
- smell
CNII
- optic
- sensory
- vision
CNIII
- oculomotor
- motor
- external eye muscles / eye movement muscles (except superior oblique and lateral rectus)
- parasympathetic fibres to ciliary muscle of eyeball for constriction and accommodation
CNIV
- trochlear
- motor
- superior oblique eye muscle
CNV
- trigeminal
- mixed
- sensory of the face, scalp, nasal/oral cavities
- muscles of mastication
- tensor tympani muscle
CNVI
- abducens
- motor
- lateral rectus muscle of eye
CNVII
- facial nerve
- mixed
- sensation: anterior 2/3 tongue taste
- motor: muscles facial expression, stapedius
- parasympathetic: salivary and lacrimal glands
CNVIII
- vestibulocochlear
- sensory
- hearing (cochlea)
- proprioception and balance (vestibular apparatus)
CNIX
- glossopharyngeal
- mixed
- sensation: eustachian tube/middle ear, carotid body and sinus, pharynx and posterior 1/3 tongue
- motor: styropharyngeus (swallowing)
- parasympathetic: salivary glands
CNX
- vagus nerve
- mixed
- sensory: general thoracic/abdominal viscera + pharynx, larynx, external ear
- motor: speech and swallowing -> soft palate, larynx, pharynx, oesophagus
- parasympathetic: cardio/resp/GI
CNXI
- accessory
- motor
- sterno(cleido)mastoid, trapezius -> shoulder shrug
CNXII
- hypoglossal
- motor
- intrinsic/extrinsic muscles of tongue
Brain imaging - general
- Structural = aim to define anatomical abnormalities USS/ CT/ MRI
- Functional = aim is to define areas of normal and abnormal brain (cortical function) PET, SPECT, fMRI, MRS
- USS
a. Useful until 15 months – anterior fontanelle open
b. Quick, easy, portable, no anaesthetic
c. Can exclude major abnormalities - CT
a. Picks up different tissue density
b. Use contrast
c. CT angiography – image vessels
d. Better than MRI for bone - MRI
a. Magnetic resonance imaging
b. Advantage
i. Best modality for - Structural injury
- Inflammation
- Ischaemia/ infarction
ii. No bony artefact - Cerebellum
- Brainstem
- Spinal cord
iii. No radiation
c. Limitations
i. Needs to be immobile
ii. Takes longer than CT
iii. Inferior to CT for – acute blood, calcium
iv. Problems with ferromagnetic radiation
d. Specific points
i. <3 month – feed and wrap
ii. 3m-6y – need anaesthesia or sedation
iv. Paediatric brain not fully myelinated until 2 years - PET
a. 3D image based on positron-emitting Radionucleotide biologically active trace
b. FDG = fludeoxyglucose is the most commonly used racer in child neurology – seizure focus hypometabolic
MRI sequences
a. T1
i. Best sequence to see anatomy and structure
ii. CSF black / water dark
iii. Grey matter grey/white matter white
b. T2
i. Best sequence to see areas of inflammation/ edema
ii. CSF white / water bright
iii. Grey matter grey/white matter black (when myelinated)
c. FLAIR
i. Fluid attenuated inversion recovery
ii. T2 with CSF signal suppressed – black
iii. Best sequence to see inflammation/ edema close to CSF (eg. near ventricles, sulci)
d. Diffusion
i. Best sequence to see acute tissue injury
ii. Describes in terms of restriction of diffusion
iii. Changes within hours
iv. Lasts for 10 days
v. DWI = qualitative
vi. ADC = quantitative
f. MR angiography
i. Best sequence to see major vessel (MR angio MR veno)
ii. INFERIOR to conventional angiography
iii. Best sequence to see blood products (but CT superior for acute blood)
g. MR spectroscopy
i. Metabolites
h. Functional MRI
i. Echo planar rapid imaging
ii. Relies on assumption that neural activity is coupled to blood flow
iii. Functional vs rest
iv. Signal produced by differences between oxy and Hb and deoxy Hb as deoxy Hb more magnetic than oxy Hb
v. BOLD (Blood Oxygen Level Dependent Contrast)
Eye movement muscles and nerves
CNIII (oculomotor)
Superior rectus: Elevation (maximal on lateral gaze)
Inferior rectus: Depression (maximal on lateral gaze)
Medial rectus: Adduction
Inferior oblique: Excyclotorsion (up+in)
CNIV (trochlear)
Superior oblique: Incyclotorsion (down+in)
CNVI (abducens)
Lateral rectus: Abduction
Diplopia - general/background
Double vision
Impairment of movement of one eye results in projection of image to one side of the macula in the paretic eye (normally projects onto macula, and does in good eye) -> two images perceived
If side by side: lateral or medial rectus
If one on top of other: obliques/superior/inferior recti
False image is ALWAYS outer most (either vertically or horizontally, also usually paler and less distinct
At the point of maximal separation, cover one eye:
- if lateral image disappears, covered eye is responsible
- if medical image disappears, covered eye is normal
Occulomotor Nerve Palsy - background
- Anatomy
a. Can result from lesions anywhere along its path beween the occulomotor nucleus in the midbrain and the extra-ocular muscles within the orbit
b. Third nerve begins in the midbrain – consists of several subnuclei that innervate the individual extraocular muscles, the eyelids and the pupils - Function
a. Motor
i. Levator muscle of eyelid
ii. Four extra-ocular muscles – MR, SR, IR, IO
b. Parasympathetic = constrict - Aetiology
a. Usually congenital in paediatrics – associated with developmental anomaly or birth trauma
b. Intracranial lesion eg. compressive lesion, aneurysm
c. Orbital disease eg. fracture, tumour, infiltration
d. CN fibrosis
e. Myasthenia gravis – may mimic CNIII palsy
Occulomotor Nerve Palsy - manifestations and complications
a. History
i. Sudden onset binocular, vertical or oblique diplopia
ii. Droopy eyelid
iii. Children with congenital CNIII palsy – no diplopia as they ignore or suppress the second image or there is superimposed amblyopia (reduced vision in one eye caused by abnormal visual development early in life, AKA lazy eye)
b. Examination
i. Key features
1. Partial or complete ptosis – more marked than Horner’s syndorme (as supplies levator palpebrae superioris)
2. Eye in a ‘down and out’ position (if complete)
3. Pupil – failure of pupil to constrict with light (parasympathetic)
ii. Pupil may be of normal size and normally reactive, dilated and poorly reactive, or dilated and non-reactive to light and near stimulus
iii. Defects in
1. Ipsilateral adduction (medial rectus)
2. Elevation (superior rectus, inferior oblique)
3. Depression (inferior rectus)
iv. Consider CNIII palsies to be complete if impairment of the majority of function of all the somatic branches is present and ptosis is complete or almost near
1. If the deficit of adduction is significant, a primary position exotropia (eye turned out) worse in gaze toward the paretic medial rectus muscle occurs
2. If the elevator muscles (eg, superior rectus or inferior oblique muscles) are involved, an ipsilateral hypotropia (eye is turned down) occurs
3. If the inferior rectus muscle is more involved, an ipsilateral hypertropia (eye is turned up) occurs
4. Complete third nerve palsies usually are associated with a large-angle exotropia and hypotropia (eye is down and out)
c. Lesions of CNIII in cavernous sinus
i. Lesions of CNIII in the cavernous sinus and superior orbital fissure often involve other cranial nerves and have the following clinical manifestations
1. Fourth cranial nerve – Vertical diplopia
2. Sixth cranial nerve – Horizontal diplopia; esotropia (inward deviation)
3. First (ophthalmic) branch of the trigeminal nerve — Pain or numbness
4. Oculosympathetic fibers – Horner syndrome
- Complications
a. Amblyopia is the major complication = 50-75% of children
i. Caused by ptosis (deprivation amblyopia), loss of accommodation and strabismus
Trochlear Nerve Palsy - background
- Anatomy
a. Longest intracranial course – prone to injury from blunt head trauma or compression from changes in intracranial pressure
b. Only cranial nerve that has a dorsal exit from the brainstem
c. Begins in the midbrain - Function
a. Pure motor – superior oblique
i. Primary action = intorsion of the eye in the primary position
ii. Secondary action = depression of the eye in an adducted position
iii. Tertiary action = abduction (especially in the abducted position) - Aetiology
a. Congenital = most common, even those presenting in adulthood
b. Acquired
i. Trauma = can occur with mild head injuries (cf. CNIII and CNVI)
ii. Microvascular disease
c. Idiopathic
Trochlear Nerve Palsy - manifestations
a. History
i. Binocular vertical diplopia and/or subjective tilting of objects (torsional diplopia)
ii. Difficulty focusing, blurred vision , dizziness
iii. Conscious or unconscious head tilt – torsional and vertical diplopia improve with head tilting to the side OPPOSITE the paralysed muscle
b. Examination
i. Ipsilateral hypertropia (deviation upward) + excyclotorsion (rotation outward) of the involved eye (as the function is intorsion and depression)
ii. Upward deviation greater when gaze is in the direction of the weak muscle (downgaze and contralateral horizontal gaze)
iii. Deviation greater in ipsilateral head tilt
c. 3 step test
i. Which is higher (hypertropic) eye?
1. The determination of the more hypertropic eye narrows the paretic possibilities to four extraocular muscles (the ipsilateral superior oblique or inferior rectus or the contralateral inferior oblique or superior rectus)
ii. Is the hypertropia worse in right or left gaze?
1. The determination of which horizontal gaze worsens the hypertropia narrows the possible muscles involved from four to two because only two muscles act in right gaze and two in left gaze
2. The hypertropia is worse in contralateral gaze because that movement is controlled by the paretic muscle
3. Thus, worsening of the hypertropia in right gaze in a patient with left hypertropia implicates either the left superior oblique or the right superior rectus
iii. Is the hypertropia worse in right or left head tilt?
1. The determination of which head tilt worsens the hypertropia (Bielschowsky head tilt test) identifies the involved muscle
2. Hyperdeviation is worse in ipsilateral head tilt in a fourth nerve palsy because the intorsion ability of the ipsilateral superior oblique is weak and is compensated for by the other ipsilateral intorter (the superior rectus)
3. Activation of the superior rectus causes elevation of the eye and increases the hypertropia.
4. The deviation improves in contralateral head tilt, the position that typically is adopted by the patient to reduce diplopia
5. Thus, left hypertropia that worsens with right gaze and left head tilt is consistent with a left superior oblique (or fourth nerve) palsy
Abducens Nerve Palsy - background
- Anatomy
a. Sixth nerve nucleus in the dorsal pons contains all of the neurons responsible for ipsilateral horizontal gaze
b. They include the motor neurons for the ipsilateral lateral rectus muscle and the interneurons to the contralateral third nerve medial rectus muscle subnucleus in the midbrain
i. The interneurons travel through the MLF fasciculus to the contralateral third nerve subnucleus
c. It enters the substance of the cavernous sinus lateral to the internal carotid artery and medial to the ophthalmic division of the trigeminal nerve
d. The sixth nerve enters the orbit via the superior orbital fissure to innervate the lateral rectus muscle, which abducts the eye - Function
a. Abduction - Aetiology
a. MANY causes
b. Congenital
c. Demyelinating
d. Neoplastic
e. Traumatic
f. Metabolic
Abducens Nerve Palsy - background
a. History
i. Binocular horizontal diplopia
ii. Worsens with gaze toward the paretic lateral rectus muscle
iii. Early – strabismus may be present only in the gaze toward the paralysed side; with time the esotropia (a form of strabismus (eye misalignment) characterized by an inwards turn of one or both eyes) may be present with gazing straight ahead (primary position)
iv. Degree of esotropia and abduction deficit are markers of severity
b. Examination
i. Nuclear lesions
1. Result in an ipsilateral horizontal gaze palsy rather than an isolated abduction deficit alone because of involvement of the interneurons of the medial longitudinal fasciculus
2. These interneurons control contralateral medial rectus function (adduction) during attempted ipsilateral horizontal gaze
3. Ipsilateral facial nerve palsy may occur because of the close proximity of the facial and abducens nerves in the pons
4. Nuclear and fascicular lesions usually are associated with other brainstem signs (eg, hemiparesis, hemisensory loss, central Horner syndrome)
ii. Lesions of the subarachnoid space can result in unilateral or bilateral sixth nerve palsies
1. A sixth nerve palsy can occur in these patients as a nonlocalizing sign of increased intracranial pressure (ICP), due to traction of the sixth nerve
2. The sixth nerve is particularly susceptible to this phenomenon because of its long course within the subarachnoid space
3. Other neurologic symptoms (eg, headache, nausea, vomiting) and signs (eg, dorsal midbrain syndrome, papilledema) of increased ICP also may be present
Bells Palsy - key points
a. CNVII
i. Motor = control of all muscles of facial expression (including platysma)
1. Chorda tympani branch of facial nerve stapedius muscle to dampen sound
ii. Sensory = taste sensation to anterior 2/3 of the tongue
iii. Other = lacrimation and salivation
b. Bell’s palsy = acute unilateral facial nerve palsy
i. NOT associated with other cranial neuropathies or brainstem dysfunction
c. Usually develops 2/52 post viral infection – HSV, VZV, EBV, Lyme disease, Mumps
d. Active or reactivation of HSV or VZV most common cause
e. Age of onset
i. Idiopathic or post-viral facial palsy uncommon in very young children – especially infants
ii. All children <2 years with atypical features should be discussed with neurologist
f. Ramsay-Hunt = herpes zoster oticus
i. Associated with vesicles in the external auditory canal or auricle and an ipsilateral facial palsy
Bells Palsy - manifestations
- History and examination
a. Ask about the evolution of weakness. Bell’s palsy usually comes on very quickly (over hours, no more than days)
b. Ask about preceding viral infections or trauma to the head or face
c. Ask about hyperacusis (increased sensitivity to sound) and altered taste. Both are common in Bell’s palsy.
d. Ask about facial pain. Mild pain in the face or behind the ear is common in Bell’s palsy
i. Severe pain suggests that the lesion may be caused by the varicella zoster virus (VZV).
e. Confirm that all facial nerve branches are involved diffusely (with particular reference to the muscles of the upper half of the face, which are spared in upper motor neuron lesions).
f. Perform a thorough neurological examination (rest of cranial nerves, peripheral power, tone, reflexes and coordination)
g. Examine for signs of otitis media, mastoiditis or parotitis.
h. Look for skin lesions or blisters on the face or in the ear canal.
i. Confirm that blood pressure and temperature are normal. Hypertension may rarely be associated with Bell’s palsy. - Clinical manifestations
a. Upper and lower portions of the face are paretic corner of mouth droops, unable to close eye involved
b. Other features
i. Mild acute pain
ii. Hyperaccusis
iii. Altered taste (anterior 2/3 of tongue – lost in 50%)
c. Features NOT consistent with Bell’s palsy
i. Numbness and paraesthesia do NOT usually occur – ipsilateral numbness can reportedly occur with viral (especially herpes) or postviral immunological impairment of the trigeminal and the facial nerves
Bells Palsy - treatment and prognosis
- Treatment
a. Supportive = eye care
i. Lubricating ocular drops TDS
ii. Pad eye shut at night
b. Steroids = unclear role in children, beneficial in adults
i. Prednisolone (1 mg/kg/day PO) considered if within 72 hours
c. Antivirals = only if vesicular rash present - Prognosis
a. Most children recover completely; >85% of patients recover spontaneously with no residual weakness
b. 10% have mild weakness as sequelae
c. 5% have permanent facial weakness
d. Other diagnoses should be considered if no recovery
Facial palsy at birth - general
• Usually a compression neuropathy from forceps application – recovers spontaneously
• Congenital absence of the depressor angularis oris muscle causes facial asymmetry – often associated with other congenital anomalies especially of the heart
o Cosmetic defect that interferes with feeding
• Mobius syndrome = rare neurological disorder characterise by weakness or paralysis of multiple facial nerves (most commonly CNVI and CNVII)
o Can have bilateral or unilateral facial palsy
o Usually caused by symmetrical calcified infarcts in the tegmentum of the pons and medulla during mid-gestation or late fetal life
Cavernous Sinus Thrombosis - general
- Anatomy
a. Centre aspect of the brain, between sphenoid bones and sella turcica
b. Receive blood from cerebral veins and ophthalmic veins + emissary veins
c. Contents
i. Cranial nerves = CNIII, CNIV, CNV (V1, V2), CNVI
ii. Internal cerebral artery - Aetiology
a. Late complication of an infection of the central face and paranasal sinuses
b. Bacteraemia
c. Trauma
d. Infections of ear and maxillary teeth - Clinical presentation
a. Headache +/- vomiting, papilloedema
b. Focal neurological deficit
c. Seizures
d. Encephalopathy
e. CN palsies
i. Fourth cranial nerve – Vertical diplopia
ii. Sixth cranial nerve – Horizontal diplopia; esotropia (inward deviation) - Most commonly affected
iii. First (ophthalmic) branch of the trigeminal nerve — Pain or numbness
iv. Oculosympathetic fibers – Horner syndrome
f. Visual disturbance = orbital pain, chemosis, proptosis - Investigation
a. MRI brain – abnormal signal in venous sinus
Horner Syndrome - background
- Neuroanatomy
a. Horner syndrome can result from a lesion anywhere along a three-neuron sympthathetic (adrenergic) pathway that originates in the hypothalamus
b. 1st order = descends caudally from the hypothalamus to the first synapse located in the cervical spinal cord (C8-T2)
c. 2nd order = travels from the sympathetic trunk brachial plexus over the lung apex ascends to the superior cervical ganglion, located near the angle of the mandible and the bifurcation of the common carotid
d. 3rd order = ascends with the internal carotid artery through the cavernous sinus (in close proximity with CNVI); oculosympathetic pathway joins V1 division of CNV
i. Oculosympathetic fibers innervate - Iris dilator muscle
- Muller’s muscle (small smooth muscle in the eyelids responsible for a minor portion of the upper lid elevation and lower lid retraction)
- Classified based on position
a. First order = lesions of the brainstem of cervicothoracic spinal cord
b. Second order
i. Trauma or surgery involving the spinal cord, thoracic outlet or lung apex
ii. Malignancy resulting in compression
c. Third order = lesion of the internal carotid artery eg. arterial dissection, thrombosis, cavernous sinus thrombosis - Aetiology
a. ‘Congenital’ = diagnosed within 4 weeks
i. Birth related trauma
ii. Congenital infections
iii. Neuroblastoma
iv. Idiopathic
b. Acquired
i. Malignancy - Neuroblastoma
- Rhabdomyosarcoma
- Brainstem tumous (glioma)
ii. Brainstem vascular malformation
iii. Demyelination (brainstem)
iv. Carotid artery thormbosis
v. Neck trauma
vi. Post-surgical
vii. Idiopathic
Horner Syndrome - manifestations
a. Classic triad
i. Ptosis = minor (<2mm)
1. Results from paralysis of Muller’s muscle innervated by sympathetic pathway
2. Lower AND upper eyelid affected
3. Levator palpebrae is UNAFFECTED – weakness of this muscle results in more profound upper lid ptosis seen in CNIII palsies
ii. Miosis = pupil constricted
1. Degree of anisocoria more marked in dark than light
2. Associated dilation lag – asymmetry in pupillary redilation between the two eyes when the light source is moved away from the eye
iii. Anhidrosis
1. Present in central and pre-ganglionic lesions (first or second order)
2. Anhidrosis NOT a feature of post-ganglionic or third-order lesions
3. Sympathetic fibers are responsible for facial sweating and vasodilatation branch off at the superior cervical ganglion from the remainder of oculosympathetic pathway
b. Other features
i. In infants and children impaired facial flushing (Harlequin sign) often more apparent than anhidrosis
ii. Acute features of sympathetic disruption can also include ipsilateral conjunctival injection, nasal stuffiness, and increased near point of accomodation
c. Associated neurolgical signs – to identify site of lesion
i. Brainstem signs (diplopia, vertigo, ataxia, lateralized weakness) suggest a brainstem localization
ii. Myelopathic features (bilateral or ipsilateral weakness, long tract signs, sensory level, bowel and bladder impairment) suggest involvement of the cervicothoracic cord.
iii. Arm pain and/or hand weakness typical of brachial plexus lesions suggest a lesion in the lung apex.
iv. Ipsilateral extraocular pareses, particularly a sixth nerve palsy, in the absence of other brainstem signs localize the lesion to the cavernous sinus.
v. An isolated Horner syndrome accompanied by neck or head pain suggests an internal carotid dissection.
Optic Tract and Visual Fields
Optic Tract
- Optic nerve (a purely sensory outpouching of the brain)
- Optic chiasm – crossing of temporal fibres
a. Upper bitemporal hemianopia = lower fibres
i. Usually pituitary tumour
b. Lower bitemporal hemianopia = upper fibres
i. Usually craniopharyngioma - Optic tract (after optic chiasm)
- Lentigeniculate nucleus (in the thalamus)
- Optic radiation
a. Inferior fibres (superior VF) through temporal lobe (Meyer’s loop)
b. Superior fibres (inferior VF) through parietal lobe
Visual Fields
• ‘Nasal’ and ‘temporal fields’ are perceived by different halves of the eye
o Fibres perceiving the ‘temporal fields’ cross at the optic chiasm (i.e. nasal retina)
o Fibres perceiving the ‘nasal fields’ do not cross (i.e. temporal retina)
• This results in the right field of vision being perceived by the left side of the brain, and the left field of vision being perceived by the right side of the brain
• Fibres travel via the optic tract to the lateral geniculate body
• After the lateral geniculate body, the optic radiation forms
o Superior fibres (carrying the inferior visual field) pass through the parietal lobe
o Inferior fibres (carrying the superior visual field) pass through the temporal lobe
Tunnel vision - ‘concentric diminution of the field’ - cause
Glaucoma, retinal abnormalities (chorioretinitis), papilloedema, acute ischaemia
