Neurology Flashcards
Carbemazepine
- MOA
- Indication
- SE
- Monitoring
- Na channel blocker
- Partial epilepsy and GTCS
-
SJS, DRESS
Hyponatraemia (siADH) and leukopaenia
Hepatotocic
Rash
Teratogenic -> spina bifida
GI and CNS effects
First sign of toxicity is diplopia - Monitor levels for compliance, FBE, LFTs
*Cyp450 inducer*
Sodium Valproate
- MOA
- Indication
- SE
- monitoring
- Na channel blocker, incr GABA
- Partial and generalised epilepsy incl absence seizures
- drug of choice for IDIOPATHIC epilepsy - CNS SE
Tremor with toxicity
Weight gain, obesity, insulin resistance
Pancreatitis
Thrombocytopaenia (dose-related)
Alopecia
Hepatotoxic
Teratogen - CYP INHIBITOR - can increase levels of other antiepileptics
- > if used in conjunction w other antiepileptics monitor their levels
Gabapentin
- MOA
- Indication
- SE
- monitoring
- GABA analogue, binds to voltage dependent Ca channels and prevents their delivery to cell membrane and thus prevents NT release into synapse
- Adjunct for partial seizures
*WORSENS myoclonic and absence seizures* - Weight gain
Hyperactivity
Aggression
Renal excretion virtually unchanged (not metabolised first)
Lamotrigine
- MOA
- Indication
- SE
- monitoring
- Na channel blocker
- Partial and generalised seizures
-
Rash
SJS (hypersensitivity)
CNS effects
-> tremor in toxicity
Hepatic dysfunction - No need to routinely monitor levels (unless w valproate = inducer)
Phenytoin
- MOA
- Indication
- SE
- monitoring
- Na channel blocker
-
Status epilepticus
AVOID in absence seizures - SE - incl weird endo and haem stuff
Rash
Hirsutism, acne
Gum hypertrophy
Serum sickness
Ataxia/ nystagmus
Megaloblastic anaemia
Peripheral neurop
Osteoporosis/ osteomalacia
Liver dysfunction
SJS
Movement disorders
-
Levels after dose change
CYP450 inducer
Most AEDs are lipid soluble and hepaticacally metabolised. What are the exceptions?
Renally excreted: Vigabatrin, gabapentin, levetiracetam (keppra)
excitatory neuron NT
glutamate
inhibitory neuron NT
gaba
neuronal transmission
Action potential travels along neuronal axon to synaptic terminal
Na causes depolarisation of presynaptic terminal which leads to vesicular release of NT into synapse (GABA - inhibitory or glutamate - excitatory)
Drugs with behavioural side effects
GABA ethic
Keppra
AEDS with SE of drowsiness, ataxia, tremor, diplopia, headache
Na channel blockers
RF for idiopathic IC HTN
- recent weight gain
- medications
Stronger evidence
• Growth hormone
• Tetracyclines – e.g. doxycycline
• Retinoids – e.g. isotretinoin
Weaker evidence
• Thyroxine
• Corticosteroid withdrawal
• Lithium
• Nalidixic acid
• Nitrofurantoin
Idiopathic Benign intracranial hypertension (otherwise known as pseudotumour cerebri)
Definition
Causes
Clinical features
Diagnostic ix
Major risk/cx
Tx
Definition
- Raised ICP in absence of obstruction to CSF flow and with normal CSF composition
- Normal neurology except for papilloedema and an occasional VI nerve palsy
- No other cause of raised ICP evident on imaging/investigation
Causes
- Idiopathic
- Steroid withdrawal
- OCP
- Isotretinoin
- Tetracyclines (doxycycline etc)
Clinical features
- Features of raised ICP: headache, papilloedema
- Visual changes: diplopia, transient obscuration, restricted visual field, uni or bilateral abducens palsy (VI)
- Often in teenage overweight girl (idiopathic aetiology)
Ix
- LP is diagnostic with elevated pressures >250mmhg and normal CSF composition
- MRIB or CTB (normal)
Prognosis
- Risk for vision loss as high as 25% (biggest risk is infarction of optic nerve)
Tx
- Avoid/stop causative agent
- Weight loss
- Acetazolamide (carbonic anhydrase inhibitor, reduces production of CSF)
- Steroids
- Repeated LPs
- Surgical shunting
What AEDs are levels therpaueitcally indicated?
Carbemazepine
Phenytoin and phenobarbitone
Both are cyp450 inducers so monitoring levels improves AEs
What common epilepsy syndrome tends to be sleep related/occurring at night or on waking
what phase of sleep is this increased
Benign partial epilepsy of childhood with Rolandic spikes (most common seizure of childhood, 15%)
Increased in NREM sleep
Sx
75% in sleep, 25% on waking
Twitching, numbness, or tingling of one side of the child’s face or tongue, drooling, without impaired awareness (called a focal aware seizure).
Often evolve into GTCS
Not for medication
‘Benign’ because children often outgrow these by adolescence
What epilepsy syndrome do you see Classic 3Hz spike and wave discharges on EEG
Provoked by hyperventilation
Childhood Absence seizures
10s profound impairment, abrupt onset/offset
+/- eyelid movement, automatisms
What epilepsy syndrome is this?
What is the typical age group
EEG findings?
Tx?
Prognosis?
Childhood absence epilepsy (seizures last <30s w no post-ictal phase); resemble ‘day dreaming’
4-10yo (peaking 5-6 years of age)
EEG - 3hz spike and wave
Tx - 1st line ethosuxamide -> Na valproate 2nd
Seizures remit in 80% with treatment (minority ~30% have GTCS in adolescence)
What is the classic presentation of benign epilepsy of childhood and what is the age range affected typically?
7-9yo age of onset
Presentation
- Sleep related (3/4 at night or on waking) with retained awareness
- Partial upper (face/arms)
- Facial twitching, guttural vocalisations, drooling, dysphasia, speech arrest
- Often with secondary GTC
- generally normal development
- universal regression by adolescence
- no tx required
EEG: spikes in centrotemporal region
What epilepsy syndrome has an EEG with Spikes in occipital region, activated on eye closure and normal background activity
How does it usually present?
Benign occipital epilepsy
2 types
Panayiotopoulos type
- Younger age: peak onset 3-5years
- Seizures are infrequent and < 10 minutes
- Typically occur at night, shortly after the child falls asleep.
- Head and eye deviation
- Autonomic sx: Vomiting, pallor, cyanosis, apnoea, mydriasis, HR changes
- Often evolve to GTCS (or infrequently status epilepticus)
- Triggers: turning off lights, going from lighted areas to dark ones, or from dark areas to light ones
Gastaut type
- Older age: Peak onset 8-9yo
- Visual hallucinations +/- clonic eye jerking/staring
- post-ictal headache/blindness
What EEG findings are assoc w benign epilepsy of childhood with rolandic spikes?
Centrotemporal spikes (Rolandic area)
- Biphasic, in repetitive bursts
- Increased in NREM sleep
- Normal background activity
What epilepsy syndrome is associated with 4-6Hz bilateral polyspike and slow wave discharges with frontal predominance and normal background
what is its classic presentation
Juvenile myoclonic epilepsy
- Presents around 12-15 (peak) *older age group than benign rolandic epilepsy*
- Myoclonic jerks (100%) in morning, preceding first GTCS
- GTCs (100%) also tend to be ON WAKING
- Absence seizures (20-40%), incomplete LOC
- No focal neurology
Excellent response to treatment but low remission so requires lifelong tx (Valproate 1st line)
Often fx epilepsy
Treatment of Juvenile myoclonic epilepsy
Valproate 1st line
- Lifelong tx (excellent response but low rates of remission)
Vigabatrin
MOA
AE
Non-competitive inhibitor of GABA transaminase
-> reduces the degradation of GABA, leading to increased neuronal GABA concentrations
Indicated
- partial/focal seizures
- infantile spasms
AE
- Retinopathy (30% adults)
- behavioural problems
- weight gain
- psychosis
- exacerbate myoclonic seizures
What is this condition?
8yo boy with viral infectino followed by fevers, headache, behaviour change and seizures. MRI shown.
ADEM - autoimmune disease (anti-MOG Ab in 30-40%) marked by a sudden, widespread attack of inflammation in the brain and spinal cord.
CSF: mild pleocytosis (<50 lymphocytes), oligoclonal bands uncommon
MRI - Produces multiple inflammatory lesions in the brain and spinal cord, particularly in the white matter.
- Triggered by viral infections or vaccines (sx onset 1-3 weeks post infection)
- Mean age 5-8yo. Sx resemble those of MS but marked with rapid fever
- Rapidly progressive encephalopathy
- Major symptoms include fever, headache, nausea and vomiting, confusion, behavioural change, altered consciousness, vision impairment, drowsiness, seizures and coma
- CN palsies, ataxia, hemiparesis, hemiplegia etc
DDx - viral encephalitis (treat w antivirals as can’t be distinguished clincally), mitochondrial disease, organic aciduria, CNS vasculitis, malignancy, MS
Tx - empiric abx/aciclovir and steroids
- 2nd line is IVIG
- Severe cases: plasmapheresis
- Need neurocognitive followup to ensure no deficits
If further recurring events, may acutally be MS
SE valproate
Weight gain
hair loss
pancreatitis
hepatic failure
embryopathy/teratogenic
SE phenobarbitone
rash
SE clonazepam
incr secretions
Malignant hyperthermia
Cause
Presentation
tx
Reaction to volatile anaethetics in susceptible individuals
Udnerlying mutation in RYR1 gene (ryanodine receptor (type 1), located on the sarcoplasmic reticulum (SR), the organelle within skeletal muscle cells that stores calcium) resulting in incr intracellular Ca levels
Presentation due to hypercatabolic state
- fever
- tachycardia
- tachypnoea
- mixed acidosis
- ridipid muscles
- rhabdomyolysis - elvated CK
Mx
- dantrolene - muscle relaxant that works on the same channel
Infantile botulism
Cause: infection by Clostridium botulinum, which is an anaerobic spore-forming, gram-positive bacillus.
- It can be found in the soil, water, and air pollution (often linked to consumption of raw honey)
- C. botulinum spore produces a neurotoxin that causes descending paralysis
Presentation
- peak age is 3-4 months
- floppy, poor feeding, lethargy, a weak cry, and constipation.
- ptosis in the face and eyes, dilated pupils
- excessive drooling due to weak suck reflex
- shallow breathing due to respiratory suppression
- descending B/L muscle weakness
tx
- intubation and ventilation if necessary
- BIG-IV
- antitoxin if available
SE vigabatrin
weight gain
retinopathy
psychosis
SE topiramate
nephrolithiasis
weight loss
acidosis
glaucoma
SE oxcarbazepine
hyponatraemia
Neural tube defects
What causes them?
Failure of neural tube to close on days 21-26 of intrauterine life (early T1)
Assoc - folate deficiency, sodium valproate, previous NTD
Ex:
- Spina bifida (failure of vertebral arch fusion
- Meningocoele (protrusion of meninges only through vertebral defect)
- Menigomyelocoele (protrusion of meninges and spinal cord/nerves)
- Encephalocoele (midline defect of skull w brain protrusion)
- Anencephaly (large defect in meninges and skull w rudimentary brain; incompatible w life)
Friedrich’s ataxia
Cause/inheritance
Presentation - (what other organ systems are involved?)
Diagnosis
Cause/inheritance
- AR condition
- mutation (triplet repeat) in FXN gene (makes a protein called frataxin)
- porgressive degeneration of cerebellar tracts and dorsal column (sensory tract, proprioception etc) in spinal cord
Sx onset 5-15yo (always <20)
-
Motor: Progressive ataxia
- __Broad based gait
-
Sensation: Loss of sensation in arms and legs
- Absent ankle jerk (LMN sign)
- UPGOING plantars (UMN sign)
- Speech: Progressive dysarthria
- Eyes: optic atroiphy, nystagmus
- MSK: pes cavus, scoliosis
-
Cardic : hypertrophic cardiomyopathy
- -> heart failiure and arrhythmias
- Endo: DM
Diagnosis
- Genetics: AR; FXA triplet repeat (expansion indirectly correlates w age of disease onset; directly correlates w severity of cardiac disease/mortality and diabetes)
- Clinical correlation
Prognosis
- Progressive disability
- Death ~ 40s from hypertrophic cardiomyopathy (CCF or arrhythmia)
Infantile spasms
Typical age of onset
Presentation
EEG findings
Causes
Mx
- Onset <1yo
- Peak 3-7mo
- Presentation
- Arrested development/developmental regression
- Spasms of neck, trunk and extremities - symmetric, synchronous, occurring in clusters
- EEG: hypsarrhythmia (chaotic and disorganized brain electrical activity with no recognizable pattern)
- Causes
- Idiopathic (20%)
- Structural
- Cortical dysplaia
- Cerebral dysgenesis
- Lissencephaly
- Congenital infections (TORCH)
- Tuberous sclerosis
- Birth injury (HIE, IVH)
- Postnatal brain trauma
- Meningitis
- Severe hypoglycaemia
- Metabolic disease (PKU most common)
Mx
- Vigabatrin
Tuberous sclerosis - what is the inheritance pattern/genetics of this condition?
How does this play into management?
Autosomal dominant (80% new mutations)
- mutations in TSC1 or TSC2, both tumour suppressor genes
TSC1 and TSC2 -> hyperactivation of the mTOR pathway, resulting in a downstream kinase signaling cascade that can consequently lead to abnormalities in numerous cell processes, including cell cycle progression, transcription, translation, and metabolic contro
- Use mTOR inhibitors as treatment = Sirolimus, everolimus
What is this condition?
How does it present?
Lissencephaly
Group of disordered characterised by the absence of gyrae (folds) in the cerebral cortex and an abnormally small head (microcephaly)
‘Smooth brain’
Type 1 (i.e. classic) - associated with facial dysmorphism and sometimes deletions of chromosome 17p (Miller-Dieker syndrome)
- Hypotonic at birth -> spastiticity
- Developmental delay
- Infantile spasms
Type 2 ‘cobblestoning’ = Walker-Warburg syndrome
- Autosomal recessive
- Most severe form of congenital muscular dystrophy -> death before age 3
- Brain (hydrocephalus, hypotonia, weakness, occasional seizures) and eye abnormalities (ocular dysplasia (cataracts etc))
- Caused by hypoglycosylation of α-dystroglycan.
- Serum CK elevated
- Myopathic/dystrophic muscle pathology and altered α-dystroglycan
Multiple sclerosis (MS)
- definition
- RF for MS in kids
- presentation
- Ix
- Tx
- Autoimmune, B and T cell mediated -> local inflammation in CNS that results in demyelination, gliotic scarring, and axonal loss
- Recurrent CNS demyelinating lesions (white matter) at different places , separated in time and space
- Presence of oligoclonal bands can be subsituted for separating events in TIME so as to make diagnosis as early as possible and start disease modifying treatment
- Classic remissions and relapses (acute onset)
- typically slowly progressive
- Age onset >10years (usually 20-35 however; childhood onset rare 0.2-2%)
- RF: low vit D levels, positive EBV serology, HLADRB1 gene positive
- Usually presents with central isolated syndrome (CIS) ie transverse myelitis or optic neuritis, rather than ADEM. Second event occurs in the next 2 years.
-
Clinical manifestations depend on location of lesions:
- Ataxia
- Weakness (hemiparesis)
- Headache
- Sensory changes
- bladder, bowel sx
- Unilateral blurred or double vision
- Optic neurotis (optic disk swelling)
- Optic atrophy
- *Ix**
- MRI spine and brain - plaques
- LP - oligoclonal bands (in 80%), incr IgG (60%), incr protein (60%) and cells
- *Treatment**
- Steroids help w acute attacks
- IVIG
- Disease modifying agents: IFNbeta 1a, capoxone, natalizumab
- Supportive
fragile x syndrome
inheitance
features
most common cause inherited intellectual disability
M > F
XL dominant: decr level or absent MFRP due to mutation in FMR1 gene
–> genetics: triple repeat analysis (not detected on micro array or sequencing)
Facial Features:
large head (macrocephaly) and ears
long face
prominent forehead and chin
sunken eyes
midface hypoplasia
Other:
Large testes after puberty
Behavioural problems - autism, anxiety, OCD
Eye problems
CV problems - MV prolapse, aortic root dilatation
Seizures 20%
Prader Willi phenotype (obesity, hyperphagia)
DMD vs Becker MD genetics and diagnosis
both X-linked recessive with mutation in dystrophin gene (codes for dystrophin protein in muscle)
- DMD: dystrophin ABSENT
- Becker: dystrophin REDUCED -> less severe form
diagnosis w whole exon sequencing, muscle biops (fat infiltration, no dystrophin on staining) and will have elevated CK levels
diagnostic criteria NF1
Inheritance = AD (50% sporadic mutation)
2 of 7
- cafe au lait macules >5mm
- leish nodules in eye
- axillary freckling
- neurofibromas 2 or more
- optic glioma (hamartoma in iris; normally normal vision)
- distinctive osseous lesions
- first degree relative w NF1
Features of NF2
- inheritance
- diagnostic features
- presentation
- management
AD
- more severe than NF1 (NF1 90% of cases, NF2 10% of cases)
Diagnosis req 1 or more of the following:
- B/L VIII nerve (vestibulocochlear nerve) acoustic neuromas
- Unilateral VIII nerve mass as well as any 2 of: meningioma, neurofibroma, schwannoma, glioma, cataracts
- Unitlateral VIII nerve acoustic neuroma or another brain or spinal tumour (2/3) AND first degree relative w NF2
Presentaton
- cerebellar ataxia
- hearing loss
- facial nerve palsy
- headache
- cataracts in 60-80%
Mx
- Genetic counselling
- Yearly assessment w neuro exam, auditory and visual screening and BP
- 4 eyarly opthal assessment
SMA
Genetics/cause
Presentation and age of onset
Types - which is most common and most severe?
Prognosis
Rare AR condition
Lack of functional SMN protein (2x deletion of SMN1 gene ) -> progressive degeneration of anterior horn cell
Presentation
- Onset 2-3months: Progressive motor weakness and loss of function
- Infants are floppy and weak
- Diffuse symmetrical muscle weakness prox to distal
- more severe in lower > upper limbs
- absent or markedly decr tendon reflexes
- tongue fasciculations
- restrictive resp insufficiency, restrictive lung disease -> bell shaped chest
- bulbar weakness -> swallowing difficulties -> aspiration pneumonia
- follow you around with their eyes
- reduced facial expressions
- FTT (difficulty feeding)
- Scoliosis
Diagnosis
- Genetic testing is key ?SMN1 gene and # copies of SMN2 (protective; the more copies you have, the milder the disease)
- EMG: active denervation producing fibrillation potentials
4 types based on age of onset
- type 0 prenatal onset and very severe, death at birth if no resp support
- type 1 (Werdig-hoffman disease) is most severe but also most common (onset <6mo; never able to sit; death <2yrs)
- type 2 - sits independently but never stands or walks, usually survives until adulthood (onset >6mo; death 10-40yo)
- type 3- asymptomatic until early teens or adulthood then starts to regress, survival until adulthood (onset >2yo)
- type 4 is adulthood onset (20s/30s)
Prognosis poor- usually death in infancy from resp failure
Genetics of SMA
AR
- SMN 1 mutation
- Mutation in telomeric copy of the survival motor neuron gene (SMN1 produces full length SMN protein)
- Results in deficiency of SMN protein
- SMN 2 mutation
- Centromeric copy of the survival motor neuron gene (have to have this to survive until birth)
- Differns from SMN1 in that it LACKS exon 7 -> produces truncated version of SMN protein
- Incr copies (up to 8) of SMN 2 gene = less severe disease
SMA tx
chest/spinal pt
ot
ng/peg feeding for nutrition
resp
- early tx resp inf
- rsv prophylaxis (palivizumab0
- NIV, NOCTURNAL CPAP
spinal surgery
contracture mgmt
DMAs
- genetic tx
- incr smn2 gene levels/upregulation
(Nusinersin/Spinraza; viral vector genomes
Nusinersin/Spinraza
Indication
MOA
Treatment of SMA, disease modifying agent/genetic therapy
- increases SMN protein levels by inducing exon 7 insertion into SMN2 mRNA to produce full length RBA and thus SMN2 protein production
4 monthly LPs for injection
Has prolonged life expectancy in type 1 SMA from 2 to 5years of life and improved motor milestone achievement
Best results when treated pre-symptomatically
Viral vector genomes (‘Zolgensma’ = Onasemnogene Abeparvovec
)
Treatment of SMA
=gene therapy using viral vector
Single one off Injection of SMN gene
Main side effect is liver injury risk of fulminant liver failure
Risdiplam
Treatment of SMA
Oral medication
Modifies the splicing of SMN2 messenger RNA to include exon 7 resulting in an increase in the concentration of the functional SMN protein
Will be listed on PBS this year
causes of neuropathy in children in order of most common
CMT
Friedrichs ataxia/SCA
Guillon barre
Neurogeneneration
Leukodystrophy
Charchot Marię tooth disease
What is it?
Cause, genetics and classification
also known as hereditary motor and sensory neuropathy
- Group of inherited sensorimotor neuropathies (demyelinating and/or axonal degeneration) - most common cause of inherited neuropathy
- 1/2500
- *Classification**
1. Demyelinating - cmt1a most common form
2. Axonal - cmt2a
Genetic
- 90% are caused by mutations in CMT1A - loss of myelin on peripheral nerves; reduction in conduction velocity (sensory before motor)
- CMT2a - loss of peripheral neuron axons; reduction in amplitude (sensory before motor), normal conduction velocity
Sx onset late childhood
-
Peripheral neuropathy affecting most distal nerves first (glove and stocking distribution)
- Difficulty walking with frequent falls
- Contractures and weakness of ankles -> pain
- Calf (inverted champagne bottle legs), foot muscle wasting
- Reduced reflexes (ankles >knees)
- Difficulty heel walking
- Skeletal - scoliosis, pes cavus (high arched foot)
- Foot drop and toe walking
- Ears: sensorineural hearing loss
- Eyes: optic atrophy
ix
- genetics - microarray from CMT1A
- nerve conduction studies (delayed/slow motor and sensory)
- EMG
- nerve bx
TX - supportive
- orthopaedic and orthotic
- PT
- screening for DDH
- hearing, vision screening
- monitor for sleep disordered breathing in severe forms
Dejerine sottas disease
Form of charcot marie tooth (CMT3)
- Early onset (<2 years) with delayed motor development
Extremely slow motor nerve conduction velocity (<12m/sec)
Clinical features
- Developmental motor delay
- Hypotonia
- Areflexia
- DISTAL (sometimes prox) weakness
- foot deformity is common
Diagnosis
- Nerve biopsy: marked reduction in myelinated fibre density, thin myelin sheaths and onion bulb deformities
- CSF protein elevated
Seizure classification
Focal onset (unilateral)
- awareness can be intact or impaired
- can be motor (automatisms, atonic, clonic, spasms, hyperkinetic, myoclonic, tonic)
- or non motor onset (motor features aren’t the primary sx; autonomic, behaviour arrest, cognitive, emotional, sensory)
- focal can become bilateral tonic clonic
Generalised onset (bilateral involving both hemispheres)
- motor (tonic clonic or other motor ex: clonic, tonic, myoclonic, atonic, epileptic spasms)
- non motor (absence)
DDX for seizure
Jitteriness
Sleep jerks
Sleep walking
day dreaming
startle reflexes
Night terrors
Cataplexy/narcolepsy
Syncope
- vasovagal
- orthostatic
- reflex anoxic
- CHD (AS, TOF)
- arrhythmia
Breath holding
- cyanotic
- pallid (vasovagal)
CV
- stroke
- IC haemmhorage
migraine w aura
migraine variants
- torticollis of infancy
- benign paroxysmal vertigo
- acute confusional migraine
Metabolic disorders
- hypoglycaemia
- amino acidurias
Movement disorders
- tics
- motor/autistic stereotypy’s
- chorea
- dyskinesia
Triggers for syncope vs seizures
Prolongued standing
anything unpleasant
valsalva (cough, laugh, vomit, stretch, pee, breath holding,
sitting or standing from lying (orthostatic)
unusual to have trigger for seizure except in photosensitive patients
incidence of myoclonus in vasovagal/fainting
90% have myoclonus - arhythmic nad multifocal
occasional just a few twitches or symmetric and generalised
Syncope vs GTCS
- precipitating event
- falls
- convulsions
- eyes
- hallucinations
- incontinence
- tongue biting
- postictal confusion
- precipitating event
- syncope 50%
- GTCS none - falls
- syncope flaccid or stiff
- GTCS stiff - convulsions
- syncope 80%, usually <30sec, arrhythmic, multi-focal and/or generalised
- GTCS 1-2 min, rhythmic, generalised - eyes
- syncope: open, transient upwards or lateral deviation
- GTCS open, often sustained deviation - hallucinations
- syncope: late in attack
- GTCS: may precede seizure in focal epilepsy - incontinence
- syncope : common
- GTCS: common - tongue biting
- syncope: rare
- GTCS: common - post-ictal confusion
- syncope: <30sec with crying, upset lasting longer and may be fatigued, pale, clammy (are able to speak shortly after event)
- GTCS: 2-20min (are not really able to speak for some time after event)
WEst syndrome
- triad of presentation
- age onset
- most common cause
Triad of:
- Infantile spasms
- Clusters of 5-30sec apart
- Often just after waking
- Can be flexor, extensor or mixed
- Can be asymmetric or have focal features - Hypsarrhythmia (EEG) - high amplitude abnormal rhythms
- Arrest of psychomotor development (clinical)
Peak age of onset is 3-7mo
>95% onset before 2yo
60% of patients have identifiable cause
- Single most important cause is focal cortical dysplasia (surgical treatment)
Dravet syndrome
IE severe myoclonic epilepsy of infancy
Caused by mutation in SCN1a gene (Codes for neuronal VG Na channel)
- > results in premature stop codon and thus a non-functional protein
- > results in impaired Na passage and imaired GABAergic excitability
Features
- Onset of prolongued seizures triggered by fevers (vaccines -> cause fever -> seizure) in 1st year of life
- Subsequent appearance of afebrile focal, hemiclonic, myoclonic and generalised tonic clonic seizures; difficult to control w antiepileptic meds
- Environmental temp insensitivity (warm temps -> seizure)
- Developmental plateau or regression between 1-4 years
- Ataxia in childhood and adult onset crouch gait
Ix
EEG initially normal so have to test genetics (mutation in SCN1A gene)
Doose syndrmoe
IE epilepsy with myoclonic-atonic seizures
onset 1-8yrs of age in previously normal children
50% response to treatment
ketogenic diet is particularly effective in this condition
EEG: paroxysmal 4hz theta bursts, fast generalise spike and poly spike wave, photosensitivity
Doose syndrome/epilepsy with myoclonic-atonic seizures
Causes of epilepsy
Structural
Genetic
Infectious
Metabolic
Immune
Unknown
What is the commonest worldwide cause of epilepsy?
- *Neurocysticercosis**
- parasitic tissue infection caused by larval cysts of the tapeworm Taenia solium
- causes hippocampal sclerosis
- tx: praziquantel or albendazole
Grey matter disorders
What area of brain does this affect
What signs
Affecting cortex
Encephalopathy
Seizures
White matter disorders
What area of brain does this affect
What signs
Affects tracts
Spasticity
Cerebellary signs
Other motor
Progression over time, will eventually affect grey matter
Leucoencephalopathy
what is it?
REd flags for this
term that describes all of the brain white matter diseases
Red flags
- MOTOR stagnation or régression
- sudden regression with intercurrent illness or head injury
- mixed UMN and cerebellar signs
- Mixed central and peripheral motor signs
- Acquired macrocephaly
- Deterioration in school performance, personality, visual/auditory problems, new onset hyperactivity in an adolesc2ent
Leukodystrophies
Group within leukoencephalopathies
problem in myelin sheath
- Demyelinating (myelin is formed normally but is broken down)
- Dysmyelinating (abnormally formed)
- Hypomyelinating (never formed to begin with)
- Spongioform (cystic)
4 month old with developmental regression, spasticity, seizure, incr reflexes.
Galactosylceramide beta-galactosidase (GALC) activity was found to be low
What is this conditin?
Cause/genetics
Presentation
Ix and tx
Krabbe disease - Type of leukodysrophy
- lisosomal storage disorder
- AR Mutations in the GALC gene cause a deficiency of an enzyme called galactosylceramidase
- buildup of unmetabolized lipids -> degeneration of myelin sheath
Rapidly progressive in infancy
- > rapidly progressive (3-4mo) painful spasticity
- regression with irritability, spasticity/stiffness, seizures, myoclonus, visual loss
- hyperrefleixa ?absent deep tendon reflexes (peripheral neuropathy)
- death in 2-5 years
- AR genetic condition
- Diagnosis clinical, imaging and lysosomal studies
- Genetics
No treatment for this condition
HSCT
Metachromatic leukodystrophy (MLD)
Cause/genetics
pREsentation
tx
Most common leukodystrophy affecting both central and peripheral myelin (demyelation/white matter loss)
- AR Mutation in ARSA gene (arysulfate A gene)
- lysosomal sotrage disorder -> sulfatides build up in many tissues of the body -> demyelination (PNS and CNS)
80% are ‘infantile’ type
- onset of sx in 2nd year of life
- regression, ataxia and optic atrophy
- death within months to years
MRI - bilateral symmetrical confluent areas of periventricular deep white matter signal change, in particular around the atria and frontal horns with sparing of subcortical U fibres leading to a “butterfly pattern”
there is a ‘late onset’ type with normal early development and sx onset in 3rd year of life with death by 5-10years
Tx - gene therapy and BMT in early disease/prior to sx onset
Adrenoleukodystrophy
Cause/genetics
Presentation
Ix/tx
X-linked condition
Boys affected most but girls can have sx that onset later in life
Progressive peroxisomal disorder of the CNS associated with adrenal cortical failure
Clinical features variable
- onset sx 5-10yo
- behaviour change (ddx adhd) is most common initial complaint, followed by poor school performance
- disturbance of gait and coordination, loss of vision and hearing and progression to a persistent vegetative state is the typical clinical pattern if not treated early
- can be assoc w adrenal insufficiency
Dx
- Clinical features
- CSF protein elevated
- MRI evidence of white matter abnormalities
= Elevated levels of very long chain FAs
- Genetics: ABCD1 gene mutation (ATP-binding cassette subfamily D) -> ALDP protein
Tx - early tx is key!
- Steroids for adrenal insufficiency
- Lower VLCFA
- Immune modulation
- Gene therapy if caught early enough
- > Gene tx replacement
- > BMT
Zellweger syndrome
Cause
Presentation
Tx/prognosis
=cerebro-hepatorenal syndrome
AR condition - mutation in multiple PEX genes associated with peroxisome biogenesis -> unable to import proteins into peroxisomes efficiently
Clinical features
- *- dysmorphic** features (macrophephaly, flat/round face, high forehead, micrognathia, low, posterior ears, hypertelorism, cataracts, high arched palate)
- *- Liver:** cirrhosis and jaundice
- *- Renal:** PCKD
- *- Neuro**logical
- -> mental retardation, regression
- -> seizures
- -> hypotonia
- -> SNHL
- -> retinal dystrophy
- -> structural abnormalities
- MSK: Stippled epiphyses patella
Ix: elevated VLCFA + genetics
Tx - none. poor prognosis, often death within 6 months.
Alexander disease
Progressive white matter disorder (infnatile onset ~2yo, juvenile onset 4-10yo) with early onset macrocephaly+/- hydrocephalus, psychomotor retardation/regression (incl speech, swallowing) , spasticity, seizures
Death by 6yo
Anterior white matter affected first (early onset motor problems due to early involvement corticospinal tracts)
Clinical diagnosis
Brain bx on post mortem
Mutation in GFAP (glial fibriallary acidic protein gene
No treatment yet ?gene tx in future
Canavan disease
White matter disorder
Developmental regression i infancy with visual loss
Progressive head enlargement
Seizures
Spasticity
Optic atrophy
Death in childhod
Clinical diagnosis (macro-healy)
- Imaging (MRI) with white matter abnormalities, macrocephaly
- N acetylaspartic aciduria
- mutation in ASPA gene
No treatment yet ?gene tx in future
Pelizaeus Merzbacher disease
Myelin protein disorder
Hypomyelinating leucoencephalopathy (don’t form myelin sheaths at all)
Begin life with developmental delay
Slow progression
Psychomotor retardation, nystagmus, choreoathetosis, ataxia
Death in second decade
MRI - ‘tigroid’ appearance in white matter
Genetics - X-linked, mutation in PLP1 gene
Niemann pick disease
Lysosomal AR condition - accumulation in cholesterol and lipids
Acute form - rapid progression hepatosplenomegaly and neurological deterioration with death by 6yo
Subacute form - slower progression, death in 2nd/3rd decade
-cherry red spot macula
Dx - clinical
Vacuolated histiocytes
Sphingomyelinase deficiency
Genetics
Tay Sachs disease
Severe regressive disorder
AR, higher in jewish population
Abnormal startle response to noise and light is first sx
Regression at 4-6mo
Cherry red spot macula
Macrophephaly and seizures in 2nd year of life
Death in early years
Diagnosis - hexosaminadase A deficiency (lysosomal enzyme)
Mutation in HEXA gene
Wilson disease
Inherited AR disorder of copper metabolism
Leads to EXCESSIVE copper accumulation and buildup in multiple organ systems
Becomes toxic
- liver -> failure w haemolysis
- brain (basal ganglia, thalamus) -> neurological/psychological sx (parkinsonism, pseudo sclerotic, dystonia, chorea)
- eyes -> kaiser-flesher rings (present when there is neurological involvement)
Tx
- copper chelators ( D-penicillamine (DPA) or trientine (TETA), acting to increase copper excretion)
- zinc salts (ZS), which reduce copper uptake.
Relatively common (1/90 are carriers)
Mutation in ATP7B gene which transports copper across membrane
Menckes disease
X linked defect of copper transport and metabolism with abnormal intracellular copper utilisation (LOW total body Cu stores)
Carriers don’t have any sx
Motor delay
Early myoclonic seizures
Hair - brittle, abnormally shaped
Temp instability and feeding difficulties in neonatal period
Prematurity common
Shrinking of brain over time w formation of subdural haemmhorages and progressive neurological deterioration
Death by 3 yo
diagnosis based on clinical hx
decr serum Cu and caeruloplasmin levels
mutation in ATP7A gene
tx supportive
IM copper injections not evidence based
Rett syndrome
- inheritance
- presentation
- diagnosis
- prognosis
X linked condition (MECP2 gene on x chromosome)
Presentation
- Boys: lethal (FDIU) or neonatal encephalopathy
- Girls: normal early development but over time (onset >1yo) they begin in loose speech and purposeful hand movements
- Stereotyped hand movements - hand wringing
- Acquired microcephaly
- Develop seizures (GTCS)
- Autism
- Hyperventilation, apnoea, ‘sighing’ resps
Diagnosis
- clinical + genetic (MECP2 gene)
Prognosis
- Mat be non-ambulant w severe handicap for many years (survive into 30s, 40s)
- Usually death from cardiac arrthmias
Neuronal ceroid lipofuscinosis/batten disease
Presentation
Group of genetic disorders w lipopigment deposition in neurone and some visceral tissues
Normal early development
Developmental regression starting from age 2-5
- Ataxia and choreoathetosis
- Dementia
Retinal degeneration
Seizures
Diagnosis - genetic; AR
Features of mitochondrial disorders
Suspect in multisystem involvement
Ataxia,
seizures, neuropathy
Sx and signs that come and go
MRI lesions that change over time (grey and white matter)
Ix
- liver nad muscle bx
- blood and CSF lactate can be elevated (but not always)
- genetics
Tics
Definition
Causes - prim vs sec
Tx
- Sudden stereotyped and repetitive, non rhythmic
- May be quick and jerky but may also be slow
- May be simple, seemingly purposeless, or complex
- KEY - Premonitory urge or discomfort which is relieved following carrying out the tic
- Briefly suppressible but build up of tension whilst it is suppressed
- Evolves/changes over time, waxes and wanes, intermittent nature
- Reduced when distracted with active mental tasks (passive tasks ie playing on iPad, watching tv etc doesn’t count)
- most kids grow out of this by adolescence/adulthood
Must consider undiagnosed/untreated co-morbidities (ADHD, OCD, anxiety)
Causes
- idiopathic
- transient (<12mo)
- chronic (>12mo)
- Tourette syndrome (waxing and waning motor and verbal tics > 12mo) - secondary (rare)
- sydenham chorea
- post HIE
- medications
Treatment
- Education
- Clonidine
- Risperidone
- Behavioural treatments
- Treat comorbidities (ADHD w stimulant, OCD, anxiety w SSRI)
Stereotypies
- Sudden, stereotyped, repetitive movements
ex: hand flapping, twirling at wrists, hand opening, finger wiggling, body rocking, facial grimace, may be more complex sequence of multiple actions (jumping, pacing) - Predictable, commonly with excitement, stress, engrossed
- DO NOT evolve over time, persists (don’t grow out of this) but over time reduce with increased social awareness
- Give child enjoyment/positive gain
- Can have vocalisations associated (hissing, muttering etc)
Causes
- primary (normal development)
- secondary (assoc w neurodevelopment issues)
Dystonia
Twisting type movements w abnormally sustained muscle contraction
- ‘unbalanced’ co-contraction of agonist and antagonist muscles
- not rhythmic
- twisting/distortion of body posture is key
- does NOT occur during sleep
- worse with attempted movement (looks normal when not moving/sitting etc)
- task specificity (ie only when walking forwards, or only when watching tv)
- sensory trick: light touch to a specific body part reduces dystonia
Dystonia vs spasticity
Dystonia
- TONIC contraction of muscles, occurs at all speeds
- Increases with TYPE of movement
- Involuntary activation from CNS
Spasticity
- QUICK passive movement -> sudden increased resistance
- slow movement -> decr resistance
- increases with SPEED of movement
- Reflex stretch activation of muscle related to corticospinal tract injury
They can co-exist (ie in CP)
Causes of dystonia
Benign/transient
- Benign paroxysmal torticollis of infancy
Acquired or secondary to innjury
- term HIE
- kernicterus
- metabolic conditions
- neurodegen conditions
Genetic forms
Treatments for dystonia
L-DOPA trial
Baclofen
Anticholinergics (ex - artane/ benzhexol/ trihexyphenidyl, clonidine)
Benzodiazepines
Gabapentin
Benztropin
Botulinum toxin injections for focal dystonia
Deep brain stimulation if medically refractory
Myoclonus
Shock like rapid movement/twitches
Not suppressible, no premonitory urge
May be rhythmic or arrhythmic
May be physiologic (physiological sleep jerks)
May be epileptic in aetiology (need to do EEG)
Causes
- physiologic
- HIE
- autoimmune/paraneoplastic (opsoclonus myoclonus ataxia syndrome)
- metabolic (tay sachs, wilsons, mitochondrial)
- medication
Tx
- bentos
- valproate
- keppra
Tremor
Oscillating, rhythmic, involuntary
Usually single joint/fixed point but can also be an axis
Causes
- physiologic
- Metabolic
- Medicaitons
- thyroid
Chorea
Irregular, non rhythmic jerky movements
Often distal muscles or face
appears as random, purposeless
NOT suppressible (vs tics are suppressible)
Continuous, present at rest, flows from one part of body to another
Can’t maintain a fixed posture (stick out tongue - can’t maintain this position etc)
Causes
- acute - sydenham’s chorea OR SLE
- genetic
- metabolic (wilsons)
- post cardiac bypass
- Hyperthyroid
- medications/drugs (antipsychotics)
- psychogenic/functional
Treatment
- valproate
- benzo
- tetrabenazine
- haloperidol
Dyskinesia
- Nonspecific term describing an excess of movement
- Sudden abnormal movements that happen episodically
3 types:
- paroxysmal kinesigenic dyskinesia: short duration frequent events, triggered by specific movements
- paroxysmal non-kinesigenic dyskinesia: infrequent but may last hours-days
- paroxysmal exercise induced dyskinesia: after several minutes of activity/exercise
Neuroaxis and what signs does a lesion produce?
- Upper Motor Neurons
- Lower Motor Neurons
- Cerebellum
UMN
- Brain and SC
- Lesion: Increased tone (spasticity), hyperreflexia, upgoing plantar response, weakness but no wasting
LMN
- Anterior horn cell, peripheral nerve, NMJ, Muscle
- Lesion: hypotonia, reduced/absent reflexes, downgoing/equivocal plantars, weakness and wasting with fasciculations
Cerebellar
- Signs: ataxic broad-based gait, dysdiadokinesis, intention tremor, head tremor, imprecise movements in force and distance
- Horizontal nystagmus towards affected side
- Dysarthria
Floppy baby - weak vs strong
causes
Central/UMN causes (floppy STRONG, normal/brisk reflexes)
- HIE
- Congenital infections, sepsis
- Genetic/syndromal (T21, PWS, fragile x syndrome)
- Metabolic (hypothyroid, peroxisomal, prader-willi)
- Cerebral malformations
- Dysmyelinating disorders
- Spinal cord disorders
- Benign congenital hypotonia (diagnosis of exclusion)
Neuromuscular/peripheral/LMN causes (floppy WEAK, areflexic, RFM in utero, feeding and breathing difficulties)
- Anterior horn cell
- –> SMA
- Neuropathies
- –> Demyelinating and axonal infantile neuropathies
- NMJ
- –> Transient autoimmune neonatal myasthenisa
- –> Congenital myasthenic syndromes
- Muscle
- –> Congenital muscular dystrophies
- –> Congenital myopathies
- –> Congenital myotonic dystrophy
Clues to a central cause for floppy baby
- Global delay (vs isolated motor)
- Dysmorphic features
- Malformations other organs
- Reduced alertness
- Seziures
- Macro/microcephaly
- Hx difficult delivery
- Normal or brisk tendon reflexes
- Fisting of hands, scissoring on vertical suspension
Central/UMN causes (floppy STRONG, normal/brisk reflexes)
- HIE
- Congenital infections, sepsis
- Genetic/syndromal (T21, PWS, fragile x syndrome)
- Metabolic (hypothyroid, peroxisomal, prader-willi)
- Cerebral malformations
- Dysmyelinating disorders
- Spinal cord disorders
- Benign congenital hypotonia (diagnosis of exclusion)
Clues to a peripheral cause for floppy baby
Areflexia
Weakness
Reduced in utero movements, polyhydramnios
Myopathic face
Fasciculations
Muscle atrophy
Ptosis
Impaired extra ocular movements
Contractures
DDH
Orthopaedic abnormalities
Family hx
Neuromuscular/peripheral/LMN causes (floppy WEAK, areflexic, RFM in utero, feeding and breathing difficulties)
- Anterior horn cell
- –> SMA
- Neuropathies
- –> Demyelinating and axonal infantile neuropathies
- NMJ
- –> Transient autoimmune neonatal myasthenisa
- –> Congenital myasthenic syndromes
- Muscle
- –> Congenital muscular dystrophies
- –> Congenital myopathies
- –> Congenital myotonic dystrophy
Conditions in which CK is elevated
- Muscular dystrophies (markedly elevated, >1000)
- DMD
- Myotonic dystrophy
- Myopathies (normal to 300s)
- SMA (normal or mildly elevated)
- Pompe disease (glycogen storage disorder type II)
ix for floppy baby
CK level
Nerve conduction and EMG
Muscle biopsy
DMD muscle bx features
- Abnormally shaped muscle cells
- Fatty infiltration
- Nuclei are central rather than peripherally located within muscle cell
what condition is a triplet repeat disorder
myotonic dystrophy
freidrich ataxia
Disorders of the anterior horn cell
- SMA (spinal muscular atrophy)
- non 5q sma
- polio
- enterioviral infections
- Hopkins’ syndrome
- ALS (motor neuron disease)
Non-5q SMAs
Spinal muscular atrophy with resp distress
Riboflavin transporter deficiency neuronopathy - responsive to riboflavin
SMA investigation results
CK
NCS
EMG
Repetitive nerve stimulation
Genetics
CK - N/mildly elevated
Nerve conduction studies - low amplitude motor responses, sensory responses normal
EMG - active denervation of muscle
–> fibrillation, fasciculations
–> residual motor units have high amplitude
Repetitive nerve stimulation: normal
Genetic testing - SMN1 gene deletion/mutation
Guillan Barre syndrome
clinical features
complications
Ix
DDX
Tx
Prognosis
Post-infectious acute demyelinating polyneuropathy (affects peripheral nerves)
GBS features
- Onset 1-2 weeks post respiratory or gastro illness (campylobacter)
- Progressive symmetrical lower limb weakness, ascending to involve UL
- Loss of reflexes (LMN)
- Pain is common, neuropathic aetiology, poorly localised, irritability (consider in kids who are irritable and NWB)
- Can involve sensory fibres as well (tingling, dysthaesias)
- Urinary retnention or incontience
Cx
- Miller Fischer syndrome: rare severe variant involving EOM (opthalmoplegia), ataxia and Areflexia with PROXIMAL muscle weakness
- Bickerstaff encephalitis: encephalitis, ataxia, opthalmoparesis (subacute onset over ~1 week). BRISK reflexes.
- Facial nerve palsy common
- Resp failure
- Aspiration from bulbar involvement
- Autonomic sx are rare: HTN, bladder dysfunction, tachycardia
Ix
- 2/3 of following
1. CSF: raised protein and oligoclonal bands after 48 hrs of sx; WCC normal
2. Nerve conductions studies (delay/slow) - abnormal within 1st week of sx - Conduction block and reduced conduction velocity
- Sensory nerves also affected in 50%
- MRI - Nerve root enhancement
Ddx
- Tick paralysis
- Poliomyelitis (asymmetrical; pain precedes weakness; no sensory sx or ANS involvement)
Tx
- IVIG 2g/kg over 2 days or plasma exchange (equally effective)
- NOT steroids - can delay the recovery
- Tx neuropathic pain (NSAIDs, gabapentin, CS)
- Monitor for cx, may need resp support in ICU
Prognosis
- 90% recovery in children - almost all regain ability to walk
- 5% will turn out to have CIDP (chronic disease, lots of relapses) and will require long term tx
Chronic inflammation demyelinating polyneuropathy CIDP
Chronic inflammatory polyneuropathy
2 types -
Relapsing/remitting or slowly progressive course
Features
- initially looks like GBS but continue to have ongoing episodes
- Weakness - proximal and distal
- Sensory - distal, less prominent than motor involvement
- Cranial nerve and bulbar involvement in a minority
- reduced/absent reflexes
Ix
- diagnosed on nerve conduction studies
Tx
- Recurrent IVIG or plasma exchange
- steroids
- immunosuppression
CSF passage
CSF secreted by choroid plexus in lateral ventricles -> through into 3rd ventral -> cerebral aqueduct -> 4th ventricle -> SA space, bathing and coating external brain and spinal cord -> reabsorbed in dural venous sinuses via arachnoid villi
(this is why subarachnoid haemmhorages have frank blood from LP that DOES NOT CLEAR)
Hydrocephalus causes
- Obstruction to CSF drainage
- Blocked shunt
- Mass: Tumour/haematoma/cyst/abscess
- Congenital aqueduct stenosis
- Dandy-Walker cyst - cyst -> occlusion to exit of 4th ventricle and subsequent dilatation of 4th ventricle
- Arnold-chiari malformation: downward displacement of cerebellar tonsils and brainstem +/- spina bifida
- Increased secretion (by choroid plexus)
- Choroid plexus papilloma (v rare)
- Impaired absorption by arachnoid villi in dural venous sinuses
- dural venous sinus thrombosus cuasing venous hypertension
- Infection (toxo, CMV, Tb meningitis)
- IV or IC bleed
Anti-NMDA receptor ab are characteristic of what condition?
How does this classically present
What additional risks do these patients have?
What infection is associated with this condition as a complication?
Tx
Autoimmune encephalitis - elevated IgG +/- oligoclonal bands in CSF and elevated WCC
AntiNMDA R antibodies in CSF (15% serum neg) - directed against GluN1 subunit of NMDA Receptor
Presentation - subacute to insidious onset of sx
- prodrome in 50% of fever, headache, urti sx
- early encephalitis: seizure or movement disorders (PD-like), psychosis, cognitive and memory disturbances
- late encephalitis (1-2 weeks): language deterioration/mutism -> autonomic dysfunction
Risk of associated ovarian teratoma in 10-20% (need imaging to screen for this) or 2/3 of post-pubertal children
Associated with previous HSV encephalitis (20% of these relapse with AI encephalitis)
Tx- IVIG and streoids +/- immunosuppression (ritux is 2nd line)
What nerve is commonly affected in raised ICP
4th CN (Trochlear) - SO muscle
6th CN (abducens) - lateral rectus muscle -> outwards gaze
Due to their long pathway in CSF, get squished w incr ICP
Ddx for ring enhancing lesions on CTB
Tumour
Abscess
Causes of cerebral abscesses
- Embolisation – cyanotic congenital heart disease with R to L shunts (TOF)
- Immunodeficiency
Spread of infection from
- Endocarditis
- Meningitis
- Chronic otitis media and mastoiditis
- Sinusitis
Soft-tissue infection of face or scalp
- Orbital cellulitis
- Dental infections
- Severe complicated pneumonia
- Penetrated head injury
- VP shunt infection
EEG basics
Even - right side
Odd - left side
Space between lines is 1 sec
- (how many spikes in 1 sec = hz)
generalised - all the leads
focal - just a few leads affected
First line Treatment for most epilepsies (and exceptions)
valproate
treatment juvenile absence epilepsy
Ethosuximide is first line
Sodium valproate or lamotrigine
treatment infantile spasm
Steroids
vigabatrin
Treatment benign rolandic epilepsy
Nothing
Low dose CBZ
Treatment symptomatic focal epilepsy in infants
phenobarbitone
treatment for symptomatic focal seizure (temporal lobe or frontal lobe epilepsies)
carbamazepine
Which anticonvulsant isn’t teratogenic
lamotrigine
A 6yo child wakes from sleep with involuntary mouth movements and unable to speak. He subsequently has a GTCS
Benign rolandic epilepsy
A 2yo child initially presents with with febrile status <1y. She continues to have further febrile and afebrile seizures including myoclonic jerks. Her development is moderate-severely delayed
Dravet syndrome
A 7 month old child presents with epileptic spasms occurring in clusters, mainly on waking. She has hypsarrhythmia on EEG.
infantile spasms
A 5 year old girl presents following weeks of sudden profound impaired consciousness without loss of body tone. EEG shows a generalized 3 Hz spike wave and the seizures are induced by hyperventilation.
childhood Absence epilepsy
A 3yo M previously healthy presents with a history of daily seizures of different types including tonic, atonic, atypical absence and myoclonic. He has been commenced on multiple AED which have not improved his symptoms .
Lennox-Gastaut syndrome
(often structural/genetic and refractory to tx)
severe form of epilepsy that typically becomes apparent during infancy or early childhood.
Affected children experience several different types of seizures most commonly atonic, tonic and atypical absence seizures. Children with Lennox-Gastaut syndrome may also develop cognitive dysfunction, delays in reaching developmental milestones and behavioral problems.
Lennox-Gastaut syndrome can be caused by a variety of underlying conditions, but in some cases no cause can be identified. Lennox-Gastaut syndrome can be difficult to treat because it is resistant (refractory) to many kinds of antiseizure medications.
3 findings are necessary for the diagnosis:
- Multiple generalized seizure types
- A slow spike-and-wave pattern (less than 2.5 Hz) on EEG
- Cognitive dysfunction.
Nerve supply to urethra/genitalia/anus
Pudendal nerve S2-4
How is the perineal nerve generally injured?
vs L5 nerve root injury?
Peroneal - Fibular head -> prolonged squatting or leg crossing
L5 - Back -> disc herniation, spinal stenosis
Both present similarly
- motor: dorsiflexion
- sensory lateral calf and dorsal foot
Optic neuritis
What is it
Causes
Presentation
An inflammatory demyelinating disorder of the optic nerve that causes acute visual loss
Can be unilateral or bilateral
Causes
Can be isolated or can be due to other underlying pathologies e.g. ADEM, MS, NMO or MOG (myelin oligodendrocyte glycoprotein) optic neuritis
Presentation
- visual loss, uni or bilateral which occurs over hrs or days, peaking at 1-2 weeks
- colour desaturation
- eye pain w movement
- often occurs para/post infectious or post vaccination
Mx
- steroids
Prognosis
1/3 go on to develop MS
What is the main difference between Beckers and Duchennes muscular dystrophy
Both mutations in dystrophin gene
Duchenne - out of frame gene change (the whole gene is stuffed up) -> absent protein
- -> more severe sx
- gower’s sign 3-6 years
- waddling trendelenburg gait
- calf muscle pseudohypertrophy (replaced w fat) as a toddler
- scoliosis
- pharyngeal weakness
- resp failure
- dilated cardiomyopathy
- -> age onset 2-3 yo (normal early motor development)
- -> time to wheelchair age 13
- -> CK more elevated
Beckers - in frame gene change (only affects a portion of gene) -> reduced protein
- -> less severe
- -> age onset 5-60 yrs
- -> dilated cardiomyopathy often predominant feature in presentation
- -> time to wheelchair adulthood
What is this condition?
How might they present?
Porencephaly
Cysts or cavities within the brain that often result from infarct or haemmhorage
Sypmtoms
- Focal neurology depending on location
- Spastic hemiparesis or quadriparesis
- Optic atrophy
- Seizures
- Developmental delay
Band heterotopia
Double cortex syndrome
Type of Neuronal heterotopia (ectopic)
MRI: band of grey matter located deep to and roughly paralleling the cortex
Intractible seizures common
Women only
Schizencephaly
Clefts
Unilateral or bilateral slits or clefts within the cerebral hemispheres due to abnormal morphogenesis
Cleft may be fused or unfused – if unilateral and large can be confused for porencephalic cyst
Present with seizures, microcephaly, severe ID and partial or complete paralysis
What syndrome?
- Developmental delay + intellectual disability
- Self-injurious behavior – bite lips
- Movement disorder
- Hyperuricaemia
Lesch Nyhan Syndrome
- Metabolic disorder
- deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme, responsible for recycling purines by converting guanine and hypoxanthine into guanosine monophosphate and inosine monophosphate, respectively.
- Lack of the enzyme causes an increase in guanine and hypoxanthine, which eventually gets converted into uric acid.
- HPRT deficiency results in a spectrum of clinical presentations depending on the severity of enzyme deficiency. With an enzyme activity of less than 1.5%, Lesch Nyhan falls towards the severe end of the spectrum.
- The characteristics defining the disease are hyperuricemia (gout, kidney stones, renal failure etc), neurodevelopmental abnormalities with global developmental delay, involuntary movements, and self-injurious behavior.
NF type 1 features
Type 1
- Cutaneous = café au lait macules, axillary or inguinal freckling
- Eyes = Lisch nodules
- Tumours = peripheral neurofibromas (neurofibroma, plexiform), optic pathway glioma, CNS neoplasms, other sarcomas
- Bone abnormalities = long bone dysplasia, pseudoarthrosis, short stature, scoliosis
- Neurological = cognitive, autism, seizures
- Hypertension
NF Type 2 features
Type 2
- Vestibular schwannomas – bilateral
- Meningioma
- Schwannoma at other locations
- Glioma
- Neurofibroma
- Posterior subcapsular lenticular opacity
What syndrome/disease?
- Spinal or cerebellar haemangioblastoma
- Retinal angiomata
- Cystic lesions of kidney/pancreas/iver/epididymis
- Renal carcinoma – results in death
Von-hippel-Lindau Disease
- abnormal growth of both benign and cancerous tumors and cysts in many parts of the body
- autosomal dominant genetic condition resulting from a deletion or mutation in the VHL gene
- may experience tumors and/or cysts in up to ten parts of the body, including the brain, spine, eyes, kidneys, pancreas, adrenal glands, inner ears, reproductive tract, liver and lung:
Brain/Spinal Hemangioblastoma
Headaches, ataxia, nystagmus, back pain, numbness, hiccups
Retinal Hemangioblastoma
Floaters, retinal detachment
Endolymphatic Sac Tumor
Hearing loss, tinnitus, vertigo
Pancreatic Cysts/Tumor/Cancer
Pancreatitis (from blockage of bile ducts), diabetes (from blockage of insulin
delivery), digestion irritability, malabsorption, jaundice
Pheochromocytoma, Paraganglioma
High blood pressure, panic attacks (or post-operative adrenal insufficiency)
Kidney Cysts, Renal Cell Carcinoma
Lower back pain, hematuria, fatigue
Cystadenomas (males and females)
Pain: consider rupture, hemorrhage, torsion (possible ovarian cancer)
What syndrome/disease?
- Neuropathic limb pain
- Telangiectasias and angiokeratomas
- Corneal opacities
- Renal manifestations
Fabry disease
absent or markedly deficient activity of the lysosomal enzyme, α-galactosidase A (α-Gal A). This disorder belongs to a group of diseases known as lysosomal storage disorders.
Features of tuberous sclerosis
- Eyes = multiple retinal lesions (hamartomas; rarely affect vision)
- Neurological
- Sub-ependmyal glial nodules (SEN) - project into venticles and calcify w ‘candle dripping apperance on CT
- Sub-ependymal giant cell astrocytomas (SEGAS)
- Cortical tubers - hard nodules. may calcify
- Epilepsy, infantile spasms -> use vigabatrin for seizures
- Autism
- cognitive impairment
- Skin lesions
- Angiofibromas cheeks, nose (85%)
- hypomelanotic lesion/ash leaf macules (80%) - need woods lamp
- Shagreen patch (‘orange peel skin’ over spine),
- ungal or periungal fibromas
- fibrous plaques to forehead/scalp
- Other organ involvement = ->
- CARDIAC: rhabdomyosarcoma (40-50%, mostly benign and regress)
- RENAL: Angiomyolipoma, single or multiple cysts, hamartomas, angiomyolipoma
- LUNG: lymphangioleiomyomatosis
- DENTAL: pits in dental enamel
- GIT: hamartomatous rectal polyps
- Bone: cysts
What is a hemiplegic migraine?
Triggers
Treatment
- Unilateral weakness that accompanies a migraine headache
- Cause by a motor aura (cortical spreading depression across the motor cortex)
- Can occur in families or in one individual (sporadic)
- The hemiplegia does not have to occur with all migraine attacks
- Triggers include stress, sleep deprivation, bright lights
- Same treatments as for typical migraine, however the use of triptans for hemiplegic migraine is controversial
- No clinical trials regarding specific treatments
What AED medications are relatively CI in childhood absence epilepsy
avoid carbamazepine, gabapentin, vigabatrin and tigabine as aggravate seizures
Features of simple vs complex febrile seizures
Simple = generalised, tonicclonic seizure lasting <15 minutes that do not recur within the same illness
Complex = have one or more of the following features
o Focal features at onset or during seizure
o Duration of >15 minutes
o Recurrence within the same febrile illness
o Incomplete recovery in an hour
Risk of epilepsy following febrile seizure
Risk of future afebrile convulsions (epilepsy) is increased by
o Family history of epilepsy
o Any neurodevelopmental problem
o Atypical febrile convulsions (prolonged or focal)
Based on number of risk factors
o No risk factors: risk of subsequent epilepsy approx. 1% (similar to population risk).
o 1 risk factor: 2%.
o More than 1 risk factor: 10%.
Congenital Myotonic dystrophy
- what is it/genetics
- presentation
- diagnosis
- mx
Progressive distal muscle weakness
- Conenital/Type 1 is childhood onset (type 2 is adult onset)
Genetics
- AD
- Expansion of CTG trinucleotide repeat (DM1) and CCTG tetra nucleotide repeat in DM2
- Anticipation occurs: more severe w each generation
- Worse if inherited from mother
Presentation
- resp failure (req ventilation from birth), facial muscle weakness, feeding difficulty, hypotonia may be present from birth
- progressive distal skeletal muscle weakness and myotonia (inability to relax muscle after contraction (ie grip)
- cardiac conduction abnormalities (cardiomyopathy, arrhythmias)
- cataracts
- learning diability 50%
- Endo - hypogonadism, diabetes
ix - genetic testing for trinucleotide repeat (dm1) + clinical (shake hands w child and parent - they can’t let go quickly due to myotonia)
Mx - phenytoin or carbamazepine can help w myotonia
Prognosis - death from arrhithmia
what conditions does the NST detect?
- Cystic fibrosis
- Fatty acid oxidation defects
- organic academias
- amino acidaemias
- maternal B12 deficiency
- congenital hypothyroidism (incr TSH)
Management of raised ICP
- acute vs chronic
Acutely raised ICP
- Nurse head in midline at 45deg angle
- IV mannitol or hypertonic saline
- Normoventilation (low Co2 causes cerebral vasoconstriction w risk of hypoperfusion and elevated CO2 will worsen ICP)
- Minimise cerebral metabolism: sedation, analgesia, muslce paralysis, low:normal temp etc
- Treat the cause (steroids for cerebral oedema, surgery for blocked shunt or acute bleed etc)
Chronic
- Acetolamide: reduce cerebrospinal fluid (CSF) secretion via its action on the choroid plexus (CP)
- Steroids (for inflammatory aetiolgoy)
- Shunt insertion
- Treat underlying cause
*
Causes of intracranial calcification
- Infection
- CMV
- Toxoplasmosis
- Tb
- HIV
- Syndromes (phakomatoses)
- Tuberous sclerosis (scattered nodules)
- NF (angiomas, gliomas)
- Sturge Weber syndrome (plaques)
- Von Hippel–Lindau disease
- Tumours
- craniopharyngomas
- pituitary adenoma etc
- Intracranial bleed/haemmhorage or post trauma
Cranial nerves
- Olfactory - smell
- Optic - vision
- Oculomotor - all EOM except superior oblique and lateral rectus
- Trochlear - Superior oblique (intorsion)
- Trigeminal - Massetor muscles and sensation to face and taste ant 2/3 tongue
- V1 - opthalmic branch
- V2 - maxillary branch
- V3 - mandibular branch
- Abducens - lateral rectus
- Facial - Facial muscles, submand/subling/lacrimal glands, taste to posterior 1/3 tongue
- Vestbulocochlear - hearing nad balance
- Glossopharyngeal - Parotid gland; gag afferent, sensation to pharynx
- Vagus - Gag efferent, vagal stuff
- Accessory - Sternomastoid, trapezius muscles
- Hypoglossal - tongue musclecs
Types of craniosynostoses and resulting cranial deformities
Causes of premature vs delayed closure of fontanelles
Premature closure
- Hyperthyroid
- Craniosynostosis
- Microcephaly
Delayed closure
- Hypothyroid
- Malnutritin
- Rickets
- Hydrocephalus
- Osteogenesis imperfecta
- Down syndrome/T13 other syndrome
Spina bifida
What is it/what causes it
What sx/signs might you appreciate
Neural tube defect caused by failure of vertebral arch fusion (L5, S1)
Can be open (spinal or cranial) or closed (skin overlying defect is intact)
Overlying spinal skin defects include: hair tuft, sinus, lipoma, pigmented lesion
Sx
- Mostly asymptomatic but neural tethering can cause cauda equina synd rome:
- motor weakness
- sensory loss
- reflex changes
- abnoral plantar response
- neurogenic bladder
- scoliosis
Lissencephaly
- Type 1 vs Type 2
Type 1 (i.e. classic)
- Associated with facial dysmorphism and sometimes deletions of chromosome 17p (Miller-Dieker syndrome)
- Hypotonic at birth -> spastiticity
- Developmental delay
- Infantile spasms
Type 2 ‘cobblestoning’ = Walker-Warburg syndrome
- Autosomal recessive
- Most severe form of congenital muscular dystrophy -> death before age 3
- Brain (hydrocephalus, hypotonia, weakness, occasional seizures) and eye abnormalities (ocular dysplasia (cataracts etc))
- Caused by hypoglycosylation of α-dystroglycan.
- Serum CK elevated
- Myopathic/dystrophic muscle pathology and altered α-dystroglycan
Types of CP
Spastic - intial hypotonia progressing to spasticity w UMN signs
- hemiplgia - one side of body (arm > leg)
- diplegia - usually both legs
- quadriplegia - all limbs involved (arms > legs)
Ataxic hypotonic - hypotonia, poor balance and incoordination
Dyskinetic - involuntary movements ++ with fluctating tone
What is this condition? what is it caused by and what is the end result/prognosis?
Aldolescent with decreased school performance and behaviour change - small involuntary movements at this stage
Further intellectual decline with onset of myoclonic jerks
History of measles as a child
SSPE = subacute sclerosing panencephalitis
- neurodegenerative condition secondary to altered host response to measles virus
- develops 5-7 years agter measles virus
- end result is myoclonus, choreoathetosis -> dementia and death
What is this condition?
5 year old male with normal development until sudden abrupt deterioration in speech -> mutism
And seizures (partial or generalised)
Lendau-Kleffner syndrome
Progressive vision loss and seizures
Developmental regression around age 2-5 age
Ataxia and choreoathetosis ( involuntary twitching or writhing)
What is this condition?
What is the vision loss due to?
Batten disease (Ceroid lipofiscinosis)
- Vision loss = retinitis pigmentosa
- AR condition
Main cause of CP
- 80% Antenatal insult (congenital infection, cerebral dysgenesis or malformation)
- 10% Intrapartum (HIE)
- 10% PN (IVH, hydrocephalus, head trauyma NAI, kernicterus, cerebral ischaeemia etc)
Transverse myelitis
- What is it?
- Causes
- Presentation
- Tx/prognosis
- Acute inflammation of cord -> paraplegia
- Causes
- viral infection: EBV, HSV, Mymps, rubella, influenza
- MS
- Radiotx
- Anterior spinal artery occlusion
- Presentation (note affects LEGS predominantly with clearly definited motor/sensory levels)
- Acute onset: weakness (flaccid -> spastic)
- Sensory loss: pain, temp, light touch
- Sphincter disturbance
- Back pain
- Fever
- Nuchal rigidity
- Prognosis - often complete spontaneous recovery; supportive tx
Myasthenia Gravis
Ix, what ab are assoc?
Presentation
Mx
What is the risk to babies born to mothers w MG?
Antibodies
- IgM and IgG Ab to AcH receptors at the NMJ (type II HS)
- only 50% Ab positivity in children (95% in adults)
15% of MG patients have thymomas
- Titin and ryanodine receptor (RyR) antibodies are found in 95% of thymoma MG
Age of onset generally ~30yo
Sx
- EOM involvement -> diplopia, ptosis
- Dyspahgia (bulbar muscles)
- Muscle fatigueability: progressive weakness with use *key*
- Proximal limb weakness
- Sad facial expression (facial muscle weakness)
Ix
- Serum AchR antibiodies
- Positive tensilon test: administer anticholinesterase w transient relief (edrophonium IV)
- Nerve stimulation test: fatiguability w repititon
Mx
- Anticholinesterase drugs (neostigmine, pyridostigmine)
- Thymectomy (role of thymus is unclear but removal can iomprove sx or cure disease)
- Steroids
- IVIG
- plasmapheresis
- Immunosuppression
Risk to babies in mothers w MG is
- Transient neonatal MG: maternal antiAcHR Ab cross placenta and cause transient neonatal disease lasting 2-3wks (similar to graves)
- weak cry, opthalmoplegia, weak facial and bulbar muscles
What is the most severe form of congenital muscular dystrophy?
what is it caused by?
Type 2 Lissencephaly (smooth brain) = Walker-Warburg syndrome
- Autosomal recessive
- Most severe form of congenital muscular dystrophy -> death before age 3
- Brain (hydrocephalus, hypotonia, weakness, occasional seizures) and eye abnormalities (ocular dysplasia (cataracts etc))
- Caused by hypoglycosylation of α-dystroglycan.
- Serum CK elevated
- Myopathic/dystrophic muscle pathology and altered α-dystroglycan
Diagnosis?
Infantile hypotonia progressing to ataxia
Developmental delay
MRIB:
Joubert syndrome
Associated later in life:
Retinal dystrophy, renal (kidney) disease, ocular colobomas, occipital encephalocele (protruding tissue at the back of the skull), fibrosis of the liver
MELAS
Acute stroke-like episodes that result in hemiparesis, hemianopia, or cortical blindness. MRI changes show non-static stroke-like lesions that don’t classically correspond to vascular territories.
Triad of features in sydenham’s chorea?
- Chorea and dysarthria
- Emotional lability (also OCD/psych illnesses assoc)
- Hypotonia
- Positive Milkmaid’s sign is when you ask the patient to grip your finger. They are able to do so but cannot sustain the contraction because of chorea and hypotonia so repeatedly release and grip again – making a “milking” motion. This sign, along with “spooning”, “touchdown” and “darting tongue’ are all signs that support the diagnosis of SC.
Stroke management
• Initial treatment is with heparin or LMWH until cardiac embolization
or dissection excluded
• If dissection excluded change to anti-platelet agent for 2 years
• If disxsection confirmed then oral anti-coagulation for at least 3 months
• Thrombolysis within 3 hours of onset of stroke is not routinely used or
recommended
Raised CSF WCC, protein, oligoclonal bands
Presentation of transverse myelitis and optic neuritis
What is this condition and what ab would you expect to be positive
WHat is the prognosis?
What is the treatment?
NMO syndrome
- Inflammatory demyelinating disease of optic nerves, brainsteam and spinal cord
- Presents post pubertally (median age 39)
Antibodies
- MOG positive 58%
- AQP4 antibodies 11% - assoc w agressive disease and 80% risk relapse and
- 50% chance of bilndness and wheelchair bound by 5 yrs after onset
- Serum Ab levels correspond w disease activity
MRI can be normal initially, develop cerebral white matter lesions over course of the disease
Treatment w
- steroids (long taper) +/- IVIG or plasma exchange
- High risk relapse so follow up with immunomodulatory tx (mycophenolate or ritux)
Role of streoids in treatment of MOG vs AQP4 Ab assoc disease (Optic Neuritis /Neuromyelitis optica spectrum disorder/ADEM)
MOG assoc is more responsive than AQP4 Ab disease
Longer steroid tail wean with MOG assoc disease due to higher risk of relapse
Opsoclonus myoclonus
Ataxia
Irritable child
Age 1-3yo
What is this condition and what are the causes and ix findings?
Opsoclonus myoclonus ataxia syndrome
- Autoimmune inflammatory reaction targeting CNS tissues
- Triggered by neoplasm or infectious event
- 50% occult neuroblastoma (more common in 1-2 yo group)
Ix
CSF: normal or mild pleocytosis; 30% oligoclonal bands
Urine catecholamines (HVA, VMA) + in 95%
MIBG
MRI full body
Treatment: resection of any tumour then steroids, IVIG -> ritux is second line
GQ1B antibodies are assoc w which neuro conditions?
Bickerstaff encephalitis - triad:
- Ataxia
- Opthalmoparesis (subacute onset over ~1 week)
- Encephalitis
- BRISK reflexes.
Miller Fischer syndrome - triad:
- Opthalmoplegia
- Ataxia
- Areflexia with PROXIMAL muscle weakness
Both rare variants of GBS
What infection is associated with GBS?
Campylobacter
What vitamin deficiency is associated with MS?
vitamin D deficiency
Distribution of weakness of
- CMT
- SMA II
- Congential myopathy
- SMA III
- LGMD (duchennes)
- FSHD
- CMT - distal
- SMA II - generalised, tongue fasciculations
- Congential myopathy - generalised
- SMA III - proximal
- LGMD (duchennes) - proximal, will have scapular winging and gower’s sign and waddling gait
- FSHD - shoulders, face, outer calves
