Neurology Flashcards
Diastematomyelia
Spinal malformation where the spinal cord is split by bony/fibrous structure, resulting in symptoms of a tethered cord (limb weakness, back pain, scoliosis).
Often associated with vertebral anomalies
Dandy-Walker malformation
Brain malformation with hypoplasia of the cerebellum (esp vermis), with often marked enlargement of the posterior fossa. Present usually in the first year of life with hydrocephalus, “sun downing”, irritability and sleepiness
Meningocele
Meninges herniate through a defect in the posterior vertebral arches, usually normal spinal cord (but may be associated with syntax or riastematomyelia)
Myelomeningocele
Both the meninges and the spinal cord herniate through the spine, often resulting in weakness of the lower extremes and bladder/bowel dysfunction
Causes of Horner syndrome
Primary neuron lesion
Brainstem stroke/tumour
Trauma to the brachial plexus
Tumour/infection of lung apex
Postganglionic neuron lesion
Dissecting carotid aneurysm
Carotid artery ischeamia
Migraine
Middle cranial fossa neoplasm
Basis of triplet repeat studies?
Some genes have inherently unstable triplet repeat regions, with the number of repeats varying in mitosis and meiosis, if the number of repeats reaches a critical level it becomes methylated and therefore inactivated, resulting in phenotypic abnormalitis
Examples of triplet repeat expansion disorders?
Fragile X syndrome
Myotonic dystrophy
Huntington disease
Spinocerebellar ataxias
(caused by expansion in the number of 3-bp repeats)
High risk of latex allergy associated with which condition?
Spina bifida - allergy to latex products due to repeated exposures (e.g. frequent surgery e.g. abdo/genitourinary, IDCs, VP shunts)
Patients are sensitised through direct mucosal exposure to products from multiple surgeries early in life
Extensor plantar responses with absent lower limb deep tendon reflexes?
Friedrich’s ataxia
- also can have cerebellar signs
Methotrexate-related leukoencephalopathy
Presents as non-specific neurological dysfunction - seizures, encephalopathy, word finding difficulties, ataxia, weakness, blurred vision
Risk factors include high cumulative dose, IT methotrexate and prolonged methotrexate clearing times
MRI brain findings with methotrexate-related leukoencephalopathy
White matter changes (particularly in the centrum semiovale) which are usually reversible
Causes of posterior reversible encephalopathy syndrome (PRES)?
Medications - cyclosporin, tacrolimus, interferon, erythropoietin
Hypertension
Features of Panayiotopoulos syndrome
Usually nocturnal and prolonged seizures (more than 5 minutes, 50% last more than 30 minutes), with ictal vomiting the most characteristic sign.
Variant of benign childhood epilepsy with occipital spikes
Charcot-Marie-Tooth: effects on tone and reflexes?
Tone normal, reflexes absent
Unilateral equinovarus and diurnal variation in gait are classical presenting features of which disease?
Segawa disease (dopa-responsive dystonia)
Classically present with unilateral equinovarus, and diurnal variation (typically toe walking which worsens throughout the day)
Gait abnormalities in autism?
Toe walking, with normal neurological examination
Prolonged febrile seizures should raise concern for?
Dravet syndrome/SCN1A channelopathy
What are the typical seizures associated with Dravet syndrome?
Hemiclonic seizures and vaccine proximal seizures
EEG changes in Dravet syndrome in children >12 months?
Normal EEG in first 12 months usually
Antiepileptics most useful in Dravet?
Sodium valproate, topiramate, stiripentol
- caution with phenytoin (may exacerbate seizures)
Frequency of positive genetic testing in Dravet syndrome?
80%
EEG: large amplitude spikes or sharp waves maximal over centrotemporal region
Benign epilepsy with centrotemporal spikes (benign rolandic epilepsy)
EEG: frequent triphasic wave pattern
Hepatic encephalopathy
EEG: low voltage pattern evolving to seizure activity
Stage 2 HIE
EEG: multifocal spikes and sharp wave pattern
Infantile spasms (hypsarrhythmia)
EEG: burst suppression or isoelectric pattern
Stage 3 HIE
vCJD (variant Creutzfeldt-Jakob disease) is the human form of what infective disease?
Bovine Spongiform Encephalopathy (BSE)
From which brain vesicle do the two cerebral hemispheres arise?
Telencephalon - a secondary brain vesicle from the prosencephalon. It has bilateral segments which become the cerebral hemispheres
From which brain vesicle does the hypothalamus arise?
Diencephalon - a secondary brain vesicle from the prosencephalon. It becomes the thalamus and hypothalamus (note: evolving evidence suggesting possibly arising from the telencephalon)
From which brain vesicle does the cerebellum arise?
Metencephalon - secondary brain vesicle which arises from the rhombencephalon. It gives rise to the cerebellum and the pons
Medication to consider in Sturge-Weber syndrome?
Aspirin - may be beneficial in reducing the number of stroke like episodes and improving neurological outcomes
Alternate name for subaponeurotic haemorrhage?
Subgaleal haemorrhage
Presenting features of subgaleal haemorrhage?
Shock (seen with tachycardia, hypotension, slow cap refill), within 30 minutes of haemorrhage a Hb drop is seen
Boggy swelling - blood crosses suture lines compared with cephalohaematoma
Cause of subgaleal haemorrhage?
Trauma to blood vessels between the skull and the scalp, almost always in the context of instrumental delivery (particularly vacuum)
Typical progression to diagnosis of Rett’s syndrome?
Initially normal development, then regression with loss of speech and purposeful hand use, stereotypic hand movements and gait abnormalities.
Head growth deceleration
Later development of seizures, autistic features, ataxia, intermittent breathing abnormalities
Usually only affects girls
Main criteria for Rett’s syndrome diagnosis?
Partial/complete loss of purposeful hand movements
Partial/complete loss of acquired spoken language
Gait abnormalities: impaired (dyspraxia) or inability to walk
Stereotypic hand movements (wringing/squeezing, clapping/tapping, mouthing, washing/rubbing)
Diagnosis to exclude in child presenting with progressive ataxia and abnormal eye movements?
Neuroblastoma
- ataxia secondary to myoclonus, and abnormal eye movements (opsoclonus)
- opsoclonus develops after myoclonus
- only 5% of neuroblastoma patients have OM, but 50% of patients with OM have neuroblastoma
New classification of “complex partial seizure”
Focal seizure without retained awareness
Definition of vein of Galen malformation?
Intracranial arteriovenous shunts located in the midline
Consist of feeding arteries (choroidal artery and anterior cerebral artery) that drain into a large venous pouch (precursor to VoG)
Presenting features of Vein of Galen malformation?
Shortness of breath, feeding issues, failure to thrive, sweating, weight loss - due to elevated preload on the right heart
Some infants also have a large HC and prominent scalp veins
Management of VoG malformation?
Manage heart failure medically until 5-6 months of age, then embolisation procedure (less risk at this age)
Indication for embolisation of Vein of Galen malformation earlier than 5-6 months of age?
Severe heart failure
Neurological deficits
Seizures
When is the most common period for a brain insult to occur in children who develop cerebral palsy?
Antenatally in 80% of cases
Intrapartum insult in <10% of patients
Association with mutation in proline-rich transmembrane protein 2 (PRRT2)?
Self-limiting and familial infantile seizures
Association with GABRA1 gene?
Juvenile myoclonic epilepsy
Association with SCN1A mutation?
Dravet syndrome - up to 80% of patients with severe myoclonic epilepsy of infancy have de novo mutations in SCN1A
MRI findings of glioma?
Typically poorly-marginated, diffusely infiltrating necrotic masses, usually supratentorial
MRI findings of craniopharyngioma?
Hyperintense cysts with a solid component, typically suprasellar (above the sella turcica, under the hypothalamus and between the temporal lobes) i.e. near pituitary gland/optic nerves
Epilepsy type: partial motor seizures, often starting in the face, mostly happen during sleep, may be associated with drooling/trouble swallowing and difficulty speaking
Benign partial epilepsy of childhood
- myoclonic twitches, can have generalised seizures (in younger kids)
- EEG shows centrotemporal spikes
- may have facial numbness or weakness
- may have unilateral sensory symptoms in limbs
First pharyngeal arch?
Mandibular arch, associated with trigeminal nerve (CN V)
Second pharyngeal arch?
Hyoid arch, associated with facial nerve (CN VII)
Third pharyngeal arch?
Associated with glossopharyngeal nerve (CN IX)
Fourth pharyngeal arch?
Associated with the superior laryngeal branch of the vagus nerve (CN X)
Fifth pharyngeal arch?
Insignificant
Sixth pharyngeal arch?
Associated with the vagus nerve via the recurrent laryngeal branch
EEG: slow spike and wave
Lennox-Gastaut syndrome
May also be seen in atypical absence epilepsy (not typical)
EEG: generalised spike and slow wave, often with repetitive trains of discharges, and especially during hyperventilation
Absence seizures
EEG: hypsarrhythmia
Infantile spasms, usually have no clear normal background activity (helps to exclude if normal background)
EEG: bilateral centrotemporal spikes and sharp waves
Landau-Kleffner syndrome (usually spreads to generalised spike wave pattern, present in >80% of sleep)
Also seen in childhood epilepsy with centrotemporal spikes/BRE, epileptic encephalopathy with continuous spikes and waves during sleep (CSWS), also seen in normal children
Typical first features of Landau-Kleffner syndrome?
Language regression/aphasia
Why are depolarising muscle relaxants (succinylcholine) and volatile anaesthetic agents (halothane, sevoflurane, isoflurane) contraindicated in Becker muscular dystrophy?
Risk of rhabdomyolysis and ‘malignant hyperthermia-like’ events
- contraindicated in all myopathies and muscular dystrophies
EEG: diffuse beta frequency activity
Patients with anxiety, with benzodiazepine use, and as a coma pattern
EEG: periodic lateralised epileptiform discharges (PLEDs)
Refer to spikes or sharp waves occurring at a regular frequency in a regionalised location, these occur as a coma pattern and are associated with a high risk of seizures if found in patients with continuous EEG monitoring in ICU
Which anticonvulsant decreases the half life of lamotrigine in a clinically significant manner?
Carbamazepine
- lamotrigine may increase the concentration of carbamazepine (increasing adverse CNS effects of carbamazepine), and carbamazepine may decrease the concentration of lamotrigine and decrease it’s efficacy
Which anticonvulsant is most likely to cause a clinically important drug reaction with lamotrigine?
Sodium valproate - increases lamotrigine levels dramatically
Which flexure lies between the rhombencephalon and the spinal cord?
Cervical flexure
Limited space for the neural tube to develop lengthways, so it folds on itself at both the cervical and cephalic flexures
Which flexure separates the two regions of the rhombencephalon?
Pontine flexure
What is the genetic abnormality found on the dystrophin gene in Duchenne muscular dystrophy?
Deletion of several exons (the dystrophin gene is the largest in the human genome)
72% of dystrophin mutations are large insertions or deletions, 20% are point mutations
Leigh disease description
Neuropathologic description characterised by demyelination, gliosis, necrosis, relative neuronal sparing and capillary proliferation in specific brain regions (most severe in basal ganglia, then brainstem, cerebellum and cerebral cortex)
MRI findings in Leigh disease
Bilaterally symmetric areas of low attenuation in the basal ganglia and brainstem, with elevated lactic acid on MR spectroscopy
Early signs of Leigh disease
Poor suck, loss of head control and motor skills
(usually presents before the age of 2)
Progression of Leigh disease
Poor appetite, vomiting, irritability, seizures
Generalised weakness, hypotonia, episodes of lactic acidosis which lead to impaired respiratory and renal function
Metachromatic leukodystrophy (MLD) description
AR white matter disease
Deficiency of ASA (required for hydrolysis of sulphated glycosphingolipids)
Clinical manifestations of metachromatic leukodystrophy (MLD)
Late infantile (12-18 months) is most common, with irritability, inability to walk and hyperextension of the knee (causing gene recurvatum)
Progresses to give upper and lower morrow neuron signs, and cognitive and psychiatric signs
Deep tendon reflexes reduced/absent
Features of progression of metachromatic leukodystrophy (MLD)?
Gradual muscle wasting, weakness and hypotonia lead to debilitation
Nystagmus, myoclonic seizures, optic atrophy and quadriparxsis appear, with mortality within the first decade of life
Neuronal ceroid lipofuscinoses (NCLs) description
Also known as Batten disease
Group of neurodegenerative disorders, the most common of the neurogenetic storage diseases
Clinical features of neuronal ceroid lipofuscinoses (NCLs)
Begin around 6-24 months, progresses rapidly
Failure to thrive, microcephaly, short stature, myoclonic jerks
Usually die before 5 years of age
In a child with neuromuscular weakness, which is the best lung function test to assess respiratory muscle weakness?
Forced vital capacity (FVC)
The cavernous sinus contains which nerves?
Oculomotor nerve (CN III), the trochlear nerve (CN IV), the ophthalmic and maxillary nerves (part 1 and part 2 of the trigeminal nerve CN V), and the abducens nerve (CN VI)
Not the facial nerve - exits brainstem between pons and medulla
Holoprosencephaly overview
When the prosencephalon (forebrain) fails to develop properly, resulting in a single brain lobe rather than two.
Tends to cause facial abnormalities (midline), ID, seizures, pituitary abnormalities
Type of CP caused by MCA infarct?
Spastic hemiplegia
Lissencephaly overview
= ‘smooth brain’
Caused by defect in neuronal migration during week 12-14
Severe developmental impairments, can cause CP
Periventricular leukomalacia overview
Causes spastic diplegia
Usually secondary to IVH and is the commonest type of CP
Spinal dysraphism overview
Failure of development of spine and spinal cord
Can cause lower limb weakness with hypertonia and hyperreflexia
First line treatment for absence seizures?
Sodium valproate
Features of optic neuritis
Inflammatory and demyelinating condition
Acute (usually monocular), visual loss, pain
RAPD (if other eye is normal)
Often visual field defect (central scotoma)
Papillitis with hyperaemia and swelling of the disc, blurring of disc margins and distended veins is seen in 1/3
MRI findings in MS
Typical lesions are ovoid, periventricular, and larger than 3mm
Seen in deep white matter/corpus callosum/periventricular regions
Prevalence of optic neuritis in MS?
Presenting feature in 15-20%, and occurs in 50% at some time throughout their illness
Much more frequently unilateral in location
Progress of MS
Typically has recurrent/relapsing pattern
Acute disseminated encephalomyelitis (ADEM) overview
Non-vasculitis inflammatory demyelinating condition, similar features to MS
Prominence of cortical signs (mental status changes, seizures)
Brain lesions involve grey-white junction
Optic neuritis is usually bilateral (but one eye can have symptoms days to months earlier)
Subacute sclerosing panencephalitis (SSPE) overview
Persistent infection with measles virus within CNS
Develops 5-10 years after measles infection
Clinical features of SSPE
Gradual and progressive psychoneurological deterioration
- personality change, seizures, myoclonus, ataxia, photosensitivity, ocular abnormalities, spasticity and coma
Systemic lupus erythematosus (SLE) overview
Present with progressive deterioration in social/mental status
More dramatic presentations include seizures, chorea, stroke, dementia and coma, may be accompanied by cranial neuropathies and/or evidence of cerebritis
Headache is a frequent complaint
Usually no MRI abnormalities (or if present, are vague)
Features of cerebral toxoplasmosis
Headache, confusion and fever, can have focal neurological deficits or seizures
Location of extradural haematoma
Between skull and dura - usually develop from injury to the middle meningeal artery or one of the branches, and are usually temporo-parietal in location
Temporal bone fracture is usually the cause
Expanding haematoma strips the dura from the skull, strong attachment hence the well defined margin
Clinical features of extradural haematoma
Can present with reduced level of consciousness or following a lucid interval
Often significant mass effect with compression of the ipsilateral lateral ventricle and dilatation of the opposite ventricle due to obstruction of the foramen of Munro
A preference for using the left hand at 12 months is suggestive of what?
Cerebral palsy - hand preference usually develops by 3 years of age, concerning if apparent before 18 months
Other early warning signs: delayed motor milestones, persistence of ‘infantile’ reflexes
Patients with NF1 who have a whole gene deletion are at an increased risk of?
Malignant peripheral nerve sheath tumours (MPNSTs)
- nearly always arise in pre-existing plexiform neurofibromas
Intellectual impact of NF1?
Learning difficulties, ADHD and ASD are more frequent in children with neurofibromatosis but severe ID is rare
Is imaging required to monitor for optic gliomas in patients with NF1?
Optic pathway gliomas are often asymptomatic and do not need treatment therefore baseline MRI not indicated
MRI is only indicated if symptomatic
What proportion of patients with NF1 have a de novo mutation?
50%
Light touch, pinprick and temperature sensations occur through which tract?
Spinothalamic tracts
Proprioception and vibration sensations occur through which tract?
Dorsal columns
Possible signs in a cortical lesion
- seizures
- encephalopathy
- involvement of higher cognitive functions (language, speech, reading)
- dysmorphic features
Possible signs in a brainstem lesion
- cranial neuropathies (double vision, facial numbness/weakness, dysphagia, hoarse voice)
- may have altered mental status
Possible signs in a spinal cord lesion
- presence of a sensory level or weakness
- involvement of bowel or urinary incontinence
Possible signs in a cerebellar lesion
Imbalance and incoordination of movements
Signs of anterior horn cell lesion
Presence of fasciculations
Possible signs in a peripheral nerve lesion
Motor or sensory loss consistent with a peripheral distribution of a nerve
Possible signs in a NMJ lesion
- can be difficult to distinguish from other peripheral causes
- may have a fatiguability characteristic, or waxing and waning pattern of motor weakness (esp ptosis or extra ocular muscles)
Possible signs in a muscle lesion
Usually more proximal than distal muscle involvement
Presence of fasciculations suggest?
Anterior horn cell lesion
CN I
Olfactory nerve
- sense of smell
CN II
Optic nerve
- visual acuity and visual fields
- afferent limb of pupillomotor action (with CN III, dilate or constricts the pupil)
CN III
Oculomotor nerve
- controls most eye movements (except those from CN IV and VI)
- efferent limb of pupillomotor action
CN IV
Trochlear nerve
- superior oblique muscle: depresses and introits the eye
- afferent limb of the corneal reflex
CN V
Trigeminal nerve
- facial sensation (divided into V1, V2, V3)
- muscles of mastication
CN VI
Abducens nerve
- lateral rectus muscle: abducts the eye
CN VII
Facial nerve
- muscles of facial expression
- efferent limb of the corneal reflex
- sense of taste in anterior two-thirds of tongue
CN VIII
Vestibulocochlear nerve
- sense of hearing
- vestibular organ: coordination of eye movements and equilibrium
CN IX
Glossopharyngeal nerve
- sense of taste and sensation in posterior two thirds of the tongue
- afferent limb of the carotid baroreceptor and gag reflexes
CN X
Vagus nerve
- muscles of the palate
- efferent limb of the baroreceptor and gag reflexes
- provides parasympathetics to most organs
CN XI
Spinal accessory nerve
- sternocleidomastoids and trapezius muscles: turn the head contralaterally and ipsilateral elevation of the shoulder, respectively
CN XII
Hypoglossal nerve
- muscles of the tongue
Upper motor neuron signs
Increased deep tendon reflexes
Babinski sign present (upping)
Increased tone, may have spasticity
No fasciculations
Lower motor neuron signs
Decreased deep tendon reflexes
Babinski sign NOT present
Decreased tone
Muscle fasciculations present
Grading of reflexes on examination
4+: hyperreflexic, presence of clonus
3+: hyperreflexic, crossed adductors may be present
2+: normal
1+: hyporeflexic
0: no reflexes
Normal Babinski reflex
Babinski is an upward extension of the big toe with stroking of the lateral to medial plantar surface of the foot
- normal in a neonate, but if present beyond 1 year of life may suggest central pathology
Location of UMN lesions?
Brain stem, spinal cord, cortex
Location of LMN lesions?
Anterior horn, plexus, peripheral nerve, NMJ, muscle
Appearances of tissues in T1 weighted MRIB
Water (CSF) = dark
Fat = bright
Brain = grey matter looks grey, white matter looks white
Appearances of tissues in T2 weighted MRIB
Water (CSF) = bright
Fat = bright
Brain = grey matter looks white, white matter looks grey
Appearances of tissues in T2 FLAIR MRIB
Water (CSF) = dark
Fat = bright
Brain = grey matter looks white, white matter looks grey
Appearances of tissues in DWI MRIB
DWI = diffusion weighted imaging
Water (CSF) = dark
Fat = dark
Brain = grey matter looks grey, white matter looks darker grey
Appearances of tissues in ADC MRIB
ADC = apparent diffusion coefficient maps
Water (CSF) = bright
Fat = dark
Brain = grey matter looks grey, white matter looks lighter grey
Clinical utility of T1 weighted MRIB
Best for visualising general anatomy
Clinical utility of T2 weighted MRIB
Best for visualising posterior fossa pathology and demyelinating lesions
Clinical utility of T2 FLAIR MRIB
Particularly useful for detecting changes in the periventricular area (as CSF shows up dark) and peripheral areas
Also good for visualising cerebral oedema
Clinical utility of DWI and ADC MRI
Low resolution images
The combination of DWI and ADC is useful for detecting acute pathology, particularly for ischaemic stroke (within a 7-10 day window) or in cases of certain tumours or infections (abscesses)
Advantages/disadvantages of CTB over MRIB
Advantages: quick, sensitive and reliable for acute changes (haemorrhage, large ischaemia, hydrocephalus, herniation), better option to look for fractures
Disadvantages: radiation, not sensitive for most CNS pathology (inflammation, periventricular leukomalacia, or ischaemia)
Intensity of multiple sequences on MRIB?
Hyperintense - refers to lighter areas
Hypointense - refers to areas that are darker
IV gadolinium is used after the above sequences obtained, if there are disturbances to the BBB then contrast will pass through and the area of pathology will enhance (such as in infection or tumours)
Definition of encephalopathy
Change in a patient’s cognitive, behavioural or mental baseline
Differentials of encephalopathy by system?
VITAMINS:
Vascular
Infectious/inflammatory
Traumatic/toxic
Autoimmune
Metabolic/malignancy
Iatrogenic/intussusception/idiopathic
Neoplastic/neurologic
Stroke/seizure/structural
What is Cushing’s triad?
Bradycardia
Irregular respirations
Wide pulse pressure
Suggests raised ICP (late sign)
Differences between lethargy, obtunded, stupor and coma?
Lethargy: can be wakened but easily falls asleep
Obtunded: similar to above but needs more stimulation to be roused
Stupor: able to be woken only with vigorous and painful stimulation but then promptly goes to sleep
Coma: unable to be awakened, even with vigorous and painful stimulation
Toxic/metabolic DDx for acute encephalopathy?
Hypoglycaemia
Hyper/hyponatraemia
Other electrolyte disturbances
Hepatic or uraemic encephalopathy
Hypercarbia
Endocrine disorders (DKA, thyroid dysfunction)
Toxic ingesion
Medication overdose
Environmental exposure (CO)
Inborn errors of metabolism
Vascular DDx for acute encephalopathy?
Diffuse anoxic (no O2) or hypoxic (low O2) injury
Arterial ischaemic stroke
Haemorrhagic stroke (subarachnoid, subdural, epidural)
Sinus venous thrombosis
Reversible posterior leukoencephalopathy syndrome
Infectious DDx for acute encephalopathy?
Sepsis
Shock
Meningitis
Encephalitis
HSV encephalitis
Neurological DDx for acute encephalopathy?
Acute demyelinating encephalomyelitis (ADEM)
Seizures (including postictal)
Status epilepticus
Complicated migraine
Structural DDx for acute encephalopathy?
Tumour or mass
Hydrocephalus
Cerebral oedema
Obstructed VP shunt
Herniation
Trauma DDx for acute encephalopathy?
Concussion
NAI
Diffuse axonal injury
Immune mediated DDx for acute encephalopathy?
Autoimmune encephalitis
Paraneoplastic encephalitis
Psychiatric DDx for acute encephalopathy?
Catatonia
Conversion
Other DDx for acute encephalopathy?
Intussusception
Malignancy
Meningitis vs encephalitis
Encephalitis refers to inflammation of brain parenchyma
Meningitis refers to inflammation of the overlying meninges
Kernig sign
Hip and knee are flexed at 90 degree, and examiner is unable to extend one leg past 135 degrees due to pain, or patient flexes the opposite knee during the manoeuvre
Low sensitivity, reasonable specificity
Brudzinski sign
Active neck flexion causes subsequent hip and knee flexion
Low sensitivity, reasonable specificity
Contraindications for LP
Patient instability
Severe coagulopathy
Skin infection over the site of the LP
Concern for impending herniation
When to consider imaging prior to LP?
Immunocompromised/immunosuppressed
History of CNS disease
New onset seizures
Presence of a focal neurological deficit or papilloedema
CSF findings in bacterial meningitis
Very high WCC count (1000-5000), usually neutrophils >80%
Low glucose
High protein
CSF findings in viral meningitis
WCC 50-1000, predominantly lymphocytes on differential (exceptions are TB and Lyme)
CSF: serum glucose ratio in viral vs bacterial meningitis?
Normal is >0.5
Bacterial: <0.5
Viral: >0.5
Clinical features of encephalitis
Fever >38 within 72 hours of presentation
Generalised/partial seizures
New onset of focal neurological findings
CSF WCC >5mm
Abnormality of brain parenchyma on imaging
Abnormality on EEG consistent with encephalitis
Complications of bacterial meningitis
Hearing loss (esp with meningococcal and Hib)
Cognitive and developmental disability
Epilepsy
Hydrocephalus
Weakness
Endocrine dysfunction (diabetes insipidus, hypothalamic dysfunction)
Overview of reversible posterior leukoencephalopathy syndrome (RPLS)
Also referred to as posterior reversible encephalopathy syndrome (PRES)
Pathogenesis thought to be multifactorial, in part due to failure of cerebral regulation of the BBB in the setting of hypertension and endothelial dysfunction with subsequent vasogenic oedema
Clinical presentation of reversible posterior leukoencephalopathy syndrome
Headaches
Encephalopathy
Visual disturbances
Seizures
Any of the above in the setting of hypertension
Risk factors for reversible posterior leukoencephalopathy syndrome
Chemotherapy or cytotoxic drugs (tacrolimus commonly)
Kidney disease
Post organ transplantation
Autoimmune disease
Eclampsia
MRI findings in reversible posterior leukoencephalopathy syndrome
Symmetrical white matter changes in the posterior cerebral hemispheres
Other Ix - consider EEG if concerned for seizures
Treatment and prognosis for reversible posterior leukoencephalopathy syndrome
Hypertension should be urgently treated
Treat any underlying aetiology, and anti epileptic agents are used to treat symptomatic seizures
Prognosis: generally favourable with full recovery
Overview of ADEM
= acute disseminated encephalomyelitis
Characterised by acute presentation of encephalopathy, presumed to be due to a single demyelinating/autoinflammatory event
Commonly triggered by infection (classically a virus 1-8 weeks prior to presentation), or less commonly, immunisations
Clinical presentation of ADEM
May include several focal neurologic deficits, including motor (hemiparesis), sensory deficits, brainstem dysfunction (e.g. oculomotor palsies, dysphagia, dysarthria) or ataxia, seizures may also be present
- can present with/without a fever
- may have other nonspecific symptoms (headache, vomiting, changes in behaviour)
- CANNOT be due to infection
- LP may show mild lymphocytosis
MRI findings in ADEM
Diffuse lesions primarily in the cerebral white matter, but may also be in the grey matter
Diagnosis of ADEM
Diagnosis of exclusion
- requires that no new clinical or MRI findings emerge three months or more after the initial episode of ADEM
Management and typical course of ADEM
- Steroids
- IVIG
Complete recovery in 60-90%, tends to only occur once (monophonic illness)
ADEM vs MS
ADEM can present similarly to first episode of paediatric MS
- MS usually will not have features of fever or encephalopathy
- MS will have multiple episodes of symptoms, ADEM is a single episode by definition
- neuroimaging in MS tends to show more discrete white matter changes, and will not involve grey or deep brain matter as seen in ADEM
Overview of anti-NMDA receptor encephalitis
An autoimmune syndrome that can present acutely or subacutely, with a wide range of symptoms
Associated with the presence of anti-N-methyl-D-aspartate (NMDA) receptor antibodies in serum and CSF
80% of cases are female
Presenting features of anti-NMDA receptor encephalitis
Neuropsychiatric, catatonia
Encephalopathy
Refractory epilepsy
Autonomic instabilities
Speech disorder
Movement disorder
Investigation for anti-NMDA receptor encephalitis
Serum and CSF for anti-NMDA receptor antibodies (sensitivity is 15% higher from CSF than from serum)
CSF: mild increase in WCC and increased protein can be seen, may have oligoclonal bands
MRI: normal in 50%, transient abnormalities otherwise
EEG: characteristic pattern called “delta brush”, and may show seizures
Consider workup for possible neoplasm
Most common neoplasm associated with anti-NMDA receptor encephalitis in women?
Ovarian teratoma
Treatment and prognosis of anti-NMDA receptor encephalitis
Treat seizures with AEDs as required
IV steroids and IVIG
Immunosuppressants such as rituximab
Treatment of any underlying neoplasm
Most have good recovery (but can be prolonged), can be associated with severe disability, mortality 4%
Risk of recurrence is present
Physical examination for suspected brain death
Must be in a coma (completely unconscious, no vocalisation or volitional activity)
Determine absence of brainstem reflexes
Flaccidity with no spontaneous movements (excluding reflex withdrawal or spinal myoclonus)
Apnoea test (complete absence of respiratory effort by formal testing, demonstrating PaCO2 >60 and >20 above baseline)
Assessment of brainstem reflexes for suspected brain death
- Pupils unreactive to light in the absence of drugs influencing pupillary activity
- No spontaneous or induced (oculocephalic, oculovestibular) eye movements
- No bulbar (facial or oral pharyngeal) muscle movement
- Absence of the following reflexes: corneal, gag, cough, sucking, rooting
Role of ancillary testing in suspected brain death
Not required if patient fulfils criteria for irreversible cessation of brain function
Indicated if examination not possible (due to injuries etc) or unable to exclude confounding factors (sedation etc)
Can use EEG or cerebral blood flow assessment
Indications for neuroimaging in a child with headaches
- abnormal neurological examination or development of focal neurological symptoms/signs
- seizures
- an acute secondary headache
- headache in children <6 years or in any child who cannot describe their headache
- headache worst on waking, or waking child from sleep
- migrainous headache in child with no family history of migraines
Causes of headaches in occipital region
Cervicogenic
Arnold-Chiari malformation
Brain tumour
Vertebral artery dissection
Causes of headaches precipitated by valsalva/worse when lying down
Arnold-Chiari malformation
All causes of increased CSF pressure
Causes of headaches worse when upright
Intracranial hypotension (e.g. CSF leak)
Postural orthostatic tachycardia syndrome
Migraine
Causes of sudden onset headache
Intracranial haemorrhage
Cerebral venous sinus thrombosis
Ischaemic stroke
Cervical artery dissection
Colloid cyst
Spontaneous intracranial hypotension
Sinusitis
Meningitis/encephalitis
Most common type of primary headache in children?
Migraine
Clinical presentation of migraine
History of >5 episodes
Pain lasts 2-72 hours
Have at least 2 of the following features: bilateral (can transition to unilateral), pulsating/throbbing character, moderate to severe intensity, aggravated by routine activities
May be associated with nausea or vomiting, photophobia, phonophobia
Treatment of migraine
Healthy habits/headache hygiene
NSAIDs (avoid aspirin in children)
Triptans (e.g. sumatriptan) - avoid in hemiplegic migraine, CI in patients with CVS disease
Anti-emetics
Preventative treatments if frequent recurrence (amitriptyline, beta blockers etc)
Migraines with aura
Up to 20% of children with migraines can have auras
Most common aura is visual changes
Second most common auras are sensory changes (paraesthesias, numbness)
Lower threshold for imaging than migraines without auras
Aura must resolve spontaneously and not last longer than 60 minutes, should precede headache onset by <20 mins
Clinical presentation of hemiplegic migraine
(Can be sporadic or familial)
Present with not only motor weakness, but also without their sensory, language or visual changes concurrently preceding their headaches
During episodes, may have motor deficits, Babinski sign and unilateral hyperreflexia
[Diagnosis of exclusion after workup excluding other causes]
Hemiplegic migraine genetic panel
Most commonly CACNA1A mutation (calcium channel)
Other genes such as ATP1A2, SCN1A or PRRT2
Treatment of hemiplegic migraines
Acetazolamide for acute attacks
Beta blockers and triptans are avoided due to theoretical risk of stroke
Clinical presentation of tension headache
10 attacks in a month, 30 mins to 7 days duration
Have at least 2 of the following features:
- bilateral
- pressing or tightening quality
- mild to moderate in severity
- not aggravated by routine activity
- may have photophobia OR phonophobia
- nil nausea or vomiting
Examination and investigation of tension headache
Normal neurological examination
May have tenderness at sites of greater and lesser occipital nerves located in the posterior cranium
No investigations indicated
Treatment of tension headaches
Similar to that of migraines in the acute setting
Less evidence for preventative treatment
- if required, amitriptyline is usual first line
Behavioural interventions
Overview of pseudotumour cerebri
Previously called idiopathic intracranial HTN or benign intracranial HTN, but these terms no longer used due to risk of irreversible visual loss (i.e. not benign)
Can be divided into primary or secondary pseudotumour cerebri (PTC)
Clinical presentation of psuedotumour cerebri
Obesity is a significant risk factor
Symptoms are similar to those of raised ICP - throbbing headache, nausea/vomiting, worsens with Valsalva manoeuvre
- other symptoms include transient decreased vision, pulsatile tinnitus, flashes of light (photopsia) and double vision
- if untreated, can lead to irreversible vision loss
Criteria for diagnosis of PTC
- Opthalmological examination revealing papilloedema (OR cranial nerve VI palsy)
- Normal neurological examination
- Normal neuroimaging (including MRI brain)
- Normal CSF composition
- Elevated opening pressure on LP >25cm in non-obese children, >28cm in obese children
If papilloedema or CN VI palsy not present, probable diagnosis of PTC can be made based on what features?
If at least 3 of the following neuroimaging criteria are found:
- empty sella
- flattening of the posterior aspect of the globe
- distention of the perioptic subarachnoid space with or without a tortuous optic nerve
- transverse venous sinus stenosis
Treatment of pseudotumour cerebri?
Discontinue provoking medications
Acetazolamide is a first line treatment
Close ophthalmologic surveillance
Surgery - if symptoms refractory to treatment, if visual loss worsens, if visual fields decrease or if intractable headache is present (optic nerve fenestration or CSF shunt)
Treat headaches as per their phenotype
Prognosis of pseudotumour cerebri?
Can have permanent visual loss if not diagnosed and treated
- risk factors include higher grade papilloedema and presenting symptom of visual loss
Cerebral venous anomalies that are secondary causes of pseudotumour cerebri?
Cerebral venous sinus thrombosis
Bilateral jugular vein thrombosis or surgical ligation
Middle ear or mastoid infection
Increased RH pressure
SVC syndrome
AV fistula
Decreased CSF absorption from previous intracranial infection or subarachnoid haemorrhage
Hypercoagulable states
Medications/exposures that are secondary causes of pseudotumour cerebri?
Antibiotics: tetracycline, minocycline, doxycycline, sulfa drugs
Vitamin A and retinoids
Hormones: human growth hormone, thyroxine, anabolic steroids, levonorgestrel
Withdrawal from chronic corticosteroids
Lithium
Medical conditions that are secondary causes of pseudotumour cerebri?
Endocrine: Addison disease, hypoparathyroidism
Hypercapnia: sleep apnoea, Pickwickian syndrome
Anaemia
Renal failure
Turner syndrome
Down syndrome
Diagnostic criteria for simple febrile seizure
Ages 6 months to 6 years in developmentally normal children, with no history of afebrile seizures
One seizure in 24 hours that lasts less than 15 minutes, with no focal features
Fever of >38 within 24 hours of seizure
Complex febrile seizures
> 15 minutes, any focal features present, more than one in 24 hours, or in developmentally abnormal child
Benign Rolandic epilepsy
Self-limited childhood epilepsy with centrotemporal spikes
Childhood onset (4-8 years)
Rolandic seizures (frontal operculum): hemifacial clonus with potential spread to arm or leg, typically from sleep, prominent postictal drooling
EEG: centrotemporal spikes that are active with sleep
Treatment optional, usually carbamazepine or oxcarbazepine
Typically outgrown by 16 years
Juvenile myoclonic epilepsy
Juvenile onset (8-20 years)
Morning myoclonus, absence seizures, eventually GTCs
EEG: 4-Hz generalised spike and polyspike and wave, photosensitivity
Treat with broad spectrum AEDs: levetiracetam, valproate
Typically lifelong
Features of West syndrome
Combination of infantile spasms, hypsarrhythmia on EEG and developmental regression
Considered an epileptic encephalopathy - causes include T21, TS, HIE
Peak incidence is 4-6 months of age
Spasms are cryptogenic (if no metabolic abnormality found) or symptomatic
Management and prognosis of West syndrome
75% develop ID if untreated, and 50% with lifelong epilepsy
Improved long term outcomes if cryptogenic spasms are treated urgently (within 10 days), less clear outcomes with symptomatic spasms (and treatment is highly variable)
Treat with ACTH or steroids
- use vigabatran if due to TS
Childhood absence epilepsy
Childhood onset (4-7 years)
Absence seizures only
Normal development, cognition, examination
EEG: 3-Hz generalised spike and wave pattern
Ethosuximide usually, can also treat with valproate or lamotrigine
Lennox-Gastaut syndrome
Severe, refractory, lifelong epilepsy
Associated with significant intellectual impairment
Multiple seizure types, usually daily
- tonic seizures while asleep, also myoclonic/atonig/GTCs
Difficult to treat - clobazam, rufinadmide and CBD oil used
First afebrile seizure workup
Rule out provoked seizure
Establish risk of further unprovoked seizures
Outpatient MRI and EEG
Typically do not need AED after first seizure
Definition of status epilepticus
5 minute GTC seizure
10 minute complex partial or seizure cluster
10-15 minute absence
Treatment of status epilepticus
Buccal/intranasal midazolam
Load with levetiracetam/phenytoin
Overview of nonconvulsive status epilepticus
Typically presents with lack of return to baseline after convulsive seizures
Requires urgent EEG to diagnose
Treat with the same regime as convulsive status epilepticus
Causes of neonatal seizures
Most common: HIE, infection
Less common: IVH, stroke, hypoglycaemia, hypocalcaemia, metabolic disorders, cerebral malformations
Rx: phenobarbital, levetiracetam or phenytoin
Overview of ketogenic diet
High-fat, high-protein diet with almost no carbohydrates
Mechanism poorly understood
Avoid giving dextrose in fluids, and avoid liquid forms of medications
Overview of VNS
Provides electrical stimulation to vagus nerve
May be used in refractory epilepsy
Must be shut off before any MR imaging
Mechanism of efficacy is poorly understood (and has variable results)
AED: ACTH
Indication: West syndrome
SE: HTN, hyperglycaemia, gastric ulcers, insomnia, irritability, immune suppression
AED: clonazepam
Indication: all epilepsy types
SE: somnolence, irritability, ataxia, withdrawal seizures
AED: ethosuximide
Indication: absence seizures
SE: nausea and vomiting
AED: lacosamide
Indication: focal epilepsy
SE: dizziness, tremor, diplopia, PR INTERVAL PROLONGATION
AED: lamotrigine
Indication: generalised epilepsy, absence seizures, focal epilepsy, safe in pregnancy
SE: STEVENS-JOHNSON SYNDROME, tremor, ataxia, insomnia
Can use for bipolar or migraines
May WORSEN myoclonic seizures
AED: levetiracetam
Indication: all epilepsy types, safe in pregnancy
SE: AGGRESSION, behaviour changes
Pyridoxine (vitamin B6) may help behavioural side effect
AED: oxcarbazepine
Indication: focal epilepsy only
SE: HYPONATRAEMIA, somnolence, dizziness, diplopia, leukopenia
AED: phenobarbital
Indication: neonatal seizures, all types
SE: sedation, cognitive changes, behaviour changes, irritability
Strong P450 enzyme inducer, induces own metabolism
AED: phenytoin/fosphenytoin
Indication: mostly severe focal epilepsy or severe neonatal seizures
SE: CEREBELLAR DEGENERATION, GINGIVAL HYPERPLASIA, Stevens-Johnson syndrome, ataxia, dysarthria
Phenytoin is highly toxic if IVC extravasates (PURPLE GLOVE SYNDROME), which is why fosphenytoin is often used
AED: topiramate
Indication: all epilepsy types, 3rd line in West
SE: RENAL STONES, METABOLIC ACIDOSIS, word finding difficulties, weight loss, anhidrosis, fatigue, limb and perioral paraesthesias
AED: valproate
Indication: all epilepsy types, absence seizures
SE: HYPERAMMONAEMIA (+/- transaminitis), HEPATOTOXICITY (if <2 years), POLYCYSTIC OVARIAN SYNDROME, tremor, weight gain, lethargy, alopecia, N/V, decreased carnitine levels, pancreatitis, neutropenia
Contraindications: liver failure, mitochondrial disease and pregnancy
AED: vigabatran
Indication: West syndrome, severe focal epilepsy
SE: IRREVERSIBLE VISUAL FIELD DEFICIT (controversial), sedation, diplopia, ataxia
AED: zonisamide
Indication: all epilepsy types
SE: same side effects as topiramate, only are less frequent
Arterial ischaemic stroke
Usually presents with acute onset of unilateral face/arm or face/arm/leg weakness, often with associated aphasia or neglect
Overview of CP
Group of disorders, due to a static insult to the developing brain, leading to abnormal tone, posture and movement
The disorder is NOT progressive, but the clinical manifestations may change over time as the child develops
Types of CP
Spastic: most common (>50%), present with UMN signs and contractures
- hemiplegia, diplegia, quadriplegia
Dyskinetic: involuntary movements (think hypoxic/ischaemic injury to basal ganglia)
- choreoathetotic, dystonic
Ataxis: uncoordinated, clumsy, slow/jerky speech
CP: spastic hemiplegia
One side of the body is affected, typically an arm moreso than a leg
Often due to perinatal stroke
CP: spastic diplegia
Bilateral legs more affected than arms
Often associated with periventricular leukomalacia
CP: spastic quadriplegia
All limbs involved
Choreoathetotic CP
Chorea: dance like movements
Athetosis: writhing movements
May also be caused by kernicterus (high bilirubin leading to brain dysfunction)
Dystonic CP
Abnormal posturing
Conditions associated with CP
Intellectual disability in up to 50% of patients
Epilepsy, vision and hearing problems, speech disorders, orthopedic problems
Investigations in CP
Diagnosis predominantly based on history/exam
MRI may show evidence of prior stroke, hypoxic ischaemic injury, PVL or cortical malformations
May consider additional metabolic/genetic testing
Treatment for CP
Supportive
OT, speech therapy
Ortho: serial casting, muscle-tendon surgery
For spasticity: botox, oral antispasmodics (e.g. baclofen, benzos), intrathecal baclofen
Typical weakness pattern in brain lesion (motor cortex or internal capsule)
Often unilateral (on the CONTRALATERAL side), typically face/arm or face/arm/leg
= UMN
Other clues: if cortical - may have other cortical signs (e.g. left brain: aphasia, right brain: neglect)
Typical weakness pattern in brainstem lesion
Crossed findings: ipsilateral face, contralateral arm/leg
= UMN
Other clues: the “d” symptoms: diplopia, dysarthria, dysphagia, dysphonia
Typical weakness pattern in spinal cord lesion (corticospinal tract)
Often bilateral arm and/or leg weakness, spares the face
= UMN
Other clues: may have sphincter dysfunction - bowel/bladder incontinence, often with associated sensory level
Typical weakness pattern in spinal cord lesion (anterior horn cell)
Often bilateral arm and/or leg weakness, spares the face
= LMN
Other clues: typically no sensory changes
Typical weakness pattern in nerve root/plexus/peripheral nerve lesion
May see unilateral arm or leg weakness in a particular distribution
= LMN
Other clues: often sensory changes in same distribution, nerve root lesions (radiculopathies) are often painful
Typical weakness pattern in NMJ lesion
Bilateral proximal, fatigable weakness
Other clues: may also involve bulbar symptoms (dysarthria, dysphagia) and respiratory insufficiency, no sensory changes
Typical weakness pattern in muscle lesion
Bilateral proximal weakness
Other clues: no sensory changes, high CK
Overview of transverse myelitis
Neuroinflammatory problem of the spinal cord with rapid onset of weakness, sensory changes and bowel/bladder dysfunction
Causes of transverse myelitis
- Post-infectious (e.g. West Nile virus, herpes viruses, HIV, Lyme disease, mycoplasma, syphilis)
- CNS demyelinating disorder (MS, neuromyelitic optica, ADEM)
- associated with systemic autoimmune diseases (SLE, Sjogren, sarcoidosis)
- idiopathic
Clinical presentation of transverse myelitis
Rapidly progressing bilateral weakness over hours to days (usually legs and sometimes arms if C-spine is involved)
Most patients have a sensory level
Bowel/bladder dysfunction (often retention)
UMN signs: initially low tone and deep tendon reflexes that progress to increased tone and hyperreflexia
If C spine affected, may have respiratory arrest (if diaphragm involved)
Investigations in transverse myelitis
MRI with contrast of spinal cord: inflammatory spinal cord lesion not due to compression, vascular process, nutritional deficiency or neoplasm
- also check brain for lesions suggestive of MS
CSF: lymphocytosis with elevated protein
Treatment and prognosis of transverse myelitis
IV glucocorticoids - typically for 3-5 days
Usually at least partial recovery, may take months to years
Overview of spinal muscular atrophy (SMA)
Degeneration of the anterior horn cells (LMNs) of the spinal cord and motor nuclei (also LMNs) of the brainstem, resulting in symmetric flaccid weakness
Clinical presentation of SMA
Diffuse symmetric weakness that is more proximal than distal, typically more prominent in the lower limbs
Restrictive, progressive, respiratory insufficiency
LMN signs: reduced muscle bulk, low tone, fasciculations (including tongue), minimal to absent deep tendon reflexes
Types of SMA
Type 1: Werdnig-Hoffman disease, most severe (neonatal onset)
Type 2: sitters
Type 3: walkers
Type 4: adult onset
SMA type 1
Most severe, neonatal onset
- decreased fetal movements in utero
- weak cry, poor suck and swallow, aspiration and tongue fasciculations
- typically alert expression and normal eye movements
- majority die before 1 year of age due to respiratory insufficiency
SMA type 2
“Sitters”
Able to sit without support when placed in seated position
SMA type 3
“Walkers”
Begins after child has started walking
Typically survive into adulthood and walk until 30s to 40s
Investigation and management of SMA
Nerve conduction studies and muscle biopsy
Mutation in SMN1 gene
Supportive treatment: respiratory, nutrition, physical therapy, spinal bracing
Nusinersin - increases level of SMN protein, delays progress of disease
Overview of acute flaccid myelitis
Unknown aetiology, but suspected to be caused by enterovirus (D-68) - related to polio
Affects anterior horn cells (as in SMA and polio)
Clinical presentation of acute flaccid myelitis
Acute onset of focal limb weakness progressing over hours to days
- typically after respiratory illness 1-2 weeks prior
Respiratory failure requiring mechanical ventilation (depending on spinal level involved)
Typically NO change in mental status or seizures
Investigation, treatment and prognosis of acute flaccid myelitis
MRI of spinal cord: non-enhancing lesions largely restricted to the grey matter
CSF: usually pleocytosis
Supportive treatment, no benefit with steroids/IVIG
Recovery is generally limited
Neonatal brachial plexopathy
Cause: stretch of shoulder during birth (brachial plexus injury), RF: shoulder dystocia
Unilateral arm weakness from birth, asymmetric Moro reflex
Can have Erb palsy or Klumpke palsy
No treatment, most spontaneously resolve by 3 months (role for surgery if not)
Erb palsy
C5 and C6 injury (sometimes also C7)
“Waiter’s tip” - arm hangs by the side and is rotated medially, forearm is extended and pronated
Klumpke palsy
C8 and T1 palsy
= hand paralysis (claw hand +/- weak forearm)
Guillain-Barre syndrome
Acute paralysing illness, thought to be due to an immune response against peripheral nerves leading to demyelination
Causes: infections (especially Campylobacter), less commonly immunisations, surgery, trauma
Polyradiculoneuropathy: multiple nerve roots and peripheral nerves are affected
Clinical presentation of Guillain-Barre syndrome
Progressive, symmetric weakness that typically starts in the legs, and ascends upward with loss of deep tendon reflexes
Can have severe respiratory muscle weakness
Pain and paraesthesias are common
Dysautonomia is also common
Symptoms usually progress over 2 weeks
Alternative: Miller Fisher variant
Miller Fisher presentation of Guillain-Barré syndrome?
- ophthalmoplegia with ataxia and areflexia
- may or may not have weakness
- associated with GQ1b antibodies (ganglioside component of the nerve)
Investigations in Guillain-Barré syndrome?
Albuminocytologic dissociation: elevated CSF protein with normal CSF white blood cell count
Nerve conduction studies: features of demyelination
Buzzword = increased F wave latency
Treatment and prognosis of Guillain-Barré syndrome?
Supportive care - respiratory support, treat autonomic dysfunction, pain control, rehabilitation
IVIG hasten recovery
Note: glucocorticoids are NOT effective
Prognosis: recovery over weeks to months, most (up to 85%) recover with minimal or no disability
Most common CNS tumour to cause precocious puberty?
Hypothalamic hamartoma
Spinal myelomeningocele, beaked midbrain on neuroimaging and downward displacement of the cerebellar vermis and tonsils is also known as?
Arnold-Chiari malformation
Also known as Chiari II malformation
Description of Chiari II malformation?
Also known as Arnold Chiari malformation
Spinal myelomeningocele, beaked midbrain on neuroimaging and downward displacement of the cerebellar vermis and tonsils
Cerebellar tonsils which are misshapen and displaced below the level of the foramen magnum?
Chiari I malformation
Small posterior fossa with cerebellar structures displaced into an occipital encephalocele?
Chiari III malformation
(the encephalocele can be high cervical or occipital, and often occurs with downward displacement of the brainstem into the spinal canal)
Term for haemorrhage between the aponeurosis and periosteum?
= subgaleal haemorrhage
The space between the aponeurosis and the periosteum is a potential space, can hold about 250ml of blood
Term for fluid between the periosteum and the scalp?
= caput succedaneum
Localised oedematous swelling of the scalp which can cross suture lines, usually benign and resolves spontaneously
Term for haemorrhage between the periosteum and the skull?
= cephalhaematoma
Haemorrhage is contained within the suture lines (therefore not usually associated with large loss of blood volume)
Moderate to severe headache, drowsiness, visual blurring, history of Crohn’s disease with a recent viral illness/poor oral intake?
Venous sinus thrombosis
Miller-Fisher syndrome
Variant of Guillain-Barre syndrome
Presents with areflexia, ataxia, opthalmoplegia that commonly affects vertical gaze (especially upward gaze)
Rapid onset of ataxia with nystagmus on lateral gaze?
Post infectious cerebellitis
Usually 2 weeks after illness
Situation where APGAR scores are most helpful?
In cases of severe and sustained neonatal depression, Apgar scores become more reliable predictors of outcome
- overall are poor predictors of long term outcome, and are not designed to predict neurologic outcome
Predictors of neurodevelopmental outcome in term infants with HIE?
- seizures at <12 hours of age
- abnormal EEG at 7 days of age
- anuria or oliguria for more than 24 hours
- neurological examination at 10 days of age
NOT Apgar scores
What is CMT1a?
Most common inherited neuropathy
Demyelinating disorder, due to duplication in PMP22 gene, AD inheritance
Presents with weakness and loss of sensation in the hands and feet
Nerve conduction: slowed conduction velocity, demyelination
Decreased CMAP amplitude as a finding on nerve conduction studies?
Suggestive of axonal loss
Standards of care in DMD management
Annual ophthal review (for boys on glucocorticoids due to risk of cataracts and raised intraocular pressure)
Annual DEXA scan once on steroids
ECG/echo 2 yearly, more frequent if symptomatic
Annual sitting spirometry
Overview of benign paroxysmal vertigo in toddlers
Rare beyond 3 years
Attacks develop suddenly: ataxia (causing child to refuse to walk), appear frightened and pale, may have N/V, may have horizontal nystagmus
Vary in duration, frequency and intensity
In what scenario is sodium valproate relatively contraindicated?
Children under 2 years - risk of fatal hepatotoxicity is highest in this age group
Which antiepileptic drug is excreted predominantly unchanged in the urine?
Gabapentin - renal elimination, half life of 5-7 hours, no significant pharmacokinetic drug interactions, not significantly protein bound
Cause of botulism?
Neuroparalytic syndrome due to the action of a neurotoxin from Clostridium botulinum (gram positive rod, spore forming, anaerobe, found on vegetables/fruit/soil)
- blocks presynaptic cholinergic transmission, affecting skeletal and smooth muscle and autonomic function
Infant botulism
Rare but potentially life-threatening neuroparalytic syndrome due to the action of a neurotoxin from Clostridium botulinum
Majority: 2-8 months old
Clinical features of botulism
- acute onset of bilateral cranial neuropathies a/w symmetric descending weakness
- typically present with constipation and poor feeding, then hypotonia and weakness +/- loss of deep tendon reflexes
- autonomic signs: decreased tears/saliva, fluctuating HR and BP, flushed skin
- CN dysfunction causes decreased gag, eye ROM, pupillary paralysis, ptosis
Can progress to respiratory failure
Diagnosis of botulinum toxin
Serum assays usually negative
Dx confirmed by isolation of C. botulinum spores from the stool
Treatment for botulinum?
Antitoxin - equine antitoxin in children >1 year, human derived immunoglobulin in infants <1 year (American answer)
Good prognosis in uncomplicated cases, mortality in hospitalised cases is <1%, recovery may take months
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Rare, acquired disorder of peripheral nerves and nerve roots
Usually symmetric, and motor > sensory
Weakness in proximal and distal muscles
Usually diminished/absent reflexes
Cardiac risk factor for brain abscesses?
Haematogenous spread is most common in children with cyanotic congenital heart disease (especially right to left shunts)
Unilateral facial nerve palsy involving the forehead?
LMN problem, therefore possibly Bell’s palsy
- BP and femorals should be checked due to a/w coarctation of the aorta
- otoscope: due to acute media as possible cause of Bell’s palsy, or may show lesions seen in Ramsay-Hunt syndrome
Primary brain vesicles?
Prosencephalon = forebrain
Mesencephalon = midbrain
Rhombencephalon = hindbrain
Auditory verbal agnosia and speech regression suggest which epilepsy syndrome?
Landau-Kleffner syndrome
- EEG: electrical status epilepticus in sleep
What is India ink staining used for?
Quick test to identify cryptococcal disease, previously first line
Now can do CSF dipstick for cryptococcal antigen (quicker)
Trigonocephaly?
Caused by premature closure of metopic suture (metopic synostosis)
Narrow, triangle shaped forehead with prominent midline ridge
Lesion in hippocampal region of mesial temporal lobe results in?
Automatisms in 60% of mesial temporal focal seizures involving the hands (fidgeting) and mouth (lip smacking)
Cause of congenital myotonic dystrophy type 1?
Expansion of a CTG trinucleotide repeat in the non-coding region of DMPK
- diagnosed with triplet repeat studies
Key neurophysiological findings in Guillain-Barre syndrome?
Slowed conduction velocities and conduction block (correlates with demyelination)
Both motor and sensory nerves are affected
Use/AEs of CBD oil in seizure management?
Effective in reducing seizures in Dravet syndrome and Lennox-Gastaut syndrome
Associated with liver enzyme derangement (particularly transaminitis)
Specific virus associated with development of ADEM?
Varicella
Features of malignant hyperthermia?
Sudden onset of extreme fever, muscle rigidity, and metabolic and respiratory acidosis, with marked CK elevation, myoglobinuria may occur due to tubular necrosis and acute renal failure
- in the setting of GA or LA exposure
Overview of periventricular leukomalacia
End stage lesion that results from hypoxic-ischaemic injury to the white matter of the developing brain
Seen in 32% of premature infants
Most commonly involves optic radiations adjacent to the trigone of lateral ventricle, and the anterior corticospinal fibres adjacent to the intraventricular foramen
Clinical features of periventricular leukomalacia
Decreased visual acuity, inferior visual field constriction, visual cognitive impairment, ocular motility disturbances, and spastic diplegia
- often preterm infants with respiratory distress requiring ventilation, feed intolerance and apnoeas etc
Which AED should be avoided in Dravet syndrome?
Sodium channel blockers such as lamotrigine and phenytoin should be avoided due to their potential to worsen seizures
Metachromatic leukodystrophy
Most common hereditary leukodystrophy, AR, lysosomal storage disorder
Most common subtype is late infantile form, presents <3 years:
Gait abnormality, muscle rigidity, vision loss, impaired swallowing
MRI: bilateral symmetrical confluent areas of periventricular deep white matter signal change (hyperintense T2) around frontal and posterior horns
Adrenoleukodystrophy
Usually presents >3 years with progessive impairment to motor and cognitive function, vision, and hearing
MRI typically involves deep white matter in parieto-occipital lobes and splenium of corpus callosum
SCN1A associated with?
Dravet syndrome
SCN1B associated with?
GEFS+ (generalised epilepsy with febrile seizures plus)
Impact of topiramate half life by other AEDs?
Increases half life: valproate
Decreases half life: phenytoin, phenobarb, carbamazepine
Visual symptoms such as scotoma or fortifications (brightly coloured spots or lines) or amaurosis (blindness or impaired vision), followed by headache or convulsions?
Benign occipital seizures
Overview of tick paralysis?
Due to a neurotoxin released by a tick, causing both decreased nerve conduction (peripheral nerve affected) and presynaptic decrease in acetylchoine release (neuromuscular junction)
Presentation and investigation of tick paralysis
Typically starts with lethargy and weakness, followed by acute ataxia, progressing to ascending flaccid paralysis
NO SENSORY INVOLVEMENT
CSF studies and neuroimaging typically normal
Rx: remove the tick, patients recover within hours
Overview of Charcot-Marie-Tooth disease
Hereditary neuropathy affecting motor and sensory nerves
Most common: type 1, caused by PMP22 gene duplication (PMP = peripheral myelin protein), AD inheritance
Presentation of Charcot-Marit-Tooth disease
Slowly progressive, symmetric distal weakness
- foot drop causing frequent tripping
Atrophy of distal muscles
Contractures of hands and feet due to weak distal muscles
- pes cavus (high arched feet)
- hammer toes
Gradual loss of distal sensation
Investigation/treatment of Charcot-Marie Tooth
Ix: EMG/NCS
Rx: supportive care (stretching, orthotics), may need surgery on feet
No disease modifying treatment or gene therapy at this stage
Overview of myasthenia gravis
Due to autoantibodies directed at acetylcholine receptors at the neuromuscular junction
Associated with thymic hyperplasia or thymoma in some patients
Presentation of myasthenia gravis
Fluctuating, fatigable weakness in proximal limb, neck, ocular, bulbar and respiratory muscles
“Fatigable” weakness: worsens with activity, improves with rest
Ocular symptoms - ptosis, binocular diplopia
Bulbar symptoms - dysarthria, dysphagia
Respiratory muscle weakness
Investigations in myasthenia gravis
Tensilon (edrophonium) test
- tensilon = acetylcholinesterase inhibitor
- positive test if after giving tensilon, immediate improvement in ptosis, opthalmoparesis or strength is observed
Acetylcholine receptor antibody testing
EMG/NCS
Treatment of myasthenia gravis
Supportive: oral acetylcholinesterase inhibitors (pyridostigmine)
Immunomodulatory therapies
- acute: IVIG or plasma exchange
- chronic: steroids or steroid-sparing agents
Some patients may benefit from thymectomy
Overview of congenital myasthenic syndromes
Due to genetic defects in the NMJ, no immune system involvement
Presentation and investigation of congenital myasthenic syndromes
Onset at birth or early childhood (lifelong)
Fatigable weakness mainly affecting the ocular and bulbar muscles
Ix: EMG/NCS, genetic testing
Treatment of congenital myasthenic syndromes
Pyridostigmine (treatment for myasthenia gravis) can WORSEN some subtypes
Albuterol or fluoxetine may be beneficial for some subtypes
Overview of transient neonatal myasthenia gravis
Due to maternal acetylcholine receptor antibodies being transferred to the fetus
Only occurs in about 10-20% of infants born to mothers with myasthenia gravis
Presentation and investigation of transient neonatal myasthenia gravis
Present with generalised weakness and hypotonia at birth, with intact deep tondon reflexes
Bulbar weakness is common, eye involvement (ptosis and opthalmoplegia) is less common)
Can be diagnosed on history, but if no known maternal myasthenia gravis then can assess response to acetylcholinesterase inhibitor (e.g. neostigmine)
Treatment and prognosis of transient neonatal myasthenia gravis
Rx: supportive - neostigmine
Prognosis: must recover within a few weeks
Mutations causing Duchenne muscular dystrophy and Becker muscle dystrophy?
- gene encoding for dystrophin, on X chromosome (largest gene identified in humans)
- dystrophin is on the cell membrane of muscle fibres
- DMD: mutation disrupts reading frame (truncated protein)
- Becker: mutations maintain reading frame (semifunctional protein)
Presentation of DMD
Onset of weakness at 2-3 years
Proximal > distal, lower > upper extremities
Cals pseudohypertrophy (replacement with connective tissue and fat)
Gowers’ sign
Systemic signs: cardiomyopathy (~15yo), ortho (fractures, scoliosis), impaired pulmonary function, decreased gastric motility
Presentation of Beckers muscular dystrophy
Semifunctional dystrophin
Later onset and milder symptoms than DMD
Still has significant cardiac involvement
Ix in DMD and BMD
CK elevated
Genetic testing: for dystrophin gene mutations
Consider NCS and muscle biopsy if diagnostic uncertainty
Treatment of DMD/BMD
Glucocorticoids - used for DMD patients (improves motor and pulmonary function, reduces scoliosis, possibly delays cardiomyopathy)
MDT supportive management - cardiac, pulmonary, orthopaedic
Prognosis of DMD/BMD
DMD - typically in wheelchair by 12, often die in late teens to 20s from respiratory insufficiency or cardiomyopathy
BMD - walk past age 16, usually survive beyond 30 years
Overview of myotonic dystrophy
Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG trinucleotide repeat, AD
Anticipation: trinucleotide repeat count increases over successive generations (next generation presents earlier, more severely)
Presentation of DM1
Congenital - hypotonia, arthrogryposis, poor feeding and respiratory failure in the neonatal period
Childhood - first symptoms include cognitive and behavioural problems by 10 years, then develop respiratory muscle weakness, myotonia, cataracts, arrhythmias
- typical pattern of weakness: facial muscles, hand intrinsic muscles, ankle dorsiflexors
CK only mildly elevated, can do genetic testing and NCS
