Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FRACP > Neurology > Flashcards

Neurology Flashcards

1
Q

Carbemazepine

  1. MOA
  2. Indication
  3. SE
  4. Monitoring
A
  1. Na channel blocker
  2. Partial epilepsy and GTCS
  3. SJS, DRESS
    Hyponatraemia (siADH) and leukopaenia
    Hepatotocic
    Rash
    Teratogenic -> spina bifida
    GI and CNS effects
    First sign of toxicity is diplopia
  4. Monitor levels for compliance, FBE, LFTs

*Cyp450 inducer*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Sodium Valproate

  1. MOA
  2. Indication
  3. SE
  4. monitoring
A
  1. Na channel blocker, incr GABA
  2. Partial and generalised epilepsy incl absence seizures
    - drug of choice for IDIOPATHIC epilepsy
  3. CNS SE
    Tremor with toxicity
    Weight gain, obesity, insulin resistance
    Pancreatitis
    Thrombocytopaenia (dose-related)
    Alopecia
    Hepatotoxic
    Teratogen
  4. CYP INHIBITOR - can increase levels of other antiepileptics
    - > if used in conjunction w other antiepileptics monitor their levels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Gabapentin

  1. MOA
  2. Indication
  3. SE
  4. monitoring
A
  1. GABA analogue, binds to voltage dependent Ca channels and prevents their delivery to cell membrane and thus prevents NT release into synapse
  2. Adjunct for partial seizures
    *WORSENS myoclonic and absence seizures*
  3. Weight gain
    Hyperactivity
    Aggression

Renal excretion virtually unchanged (not metabolised first)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Lamotrigine

  1. MOA
  2. Indication
  3. SE
  4. monitoring
A
  1. Na channel blocker
  2. Partial and generalised seizures
  3. Rash
    SJS (hypersensitivity)
    CNS effects
    -> tremor in toxicity
    Hepatic dysfunction
  4. No need to routinely monitor levels (unless w valproate = inducer)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Phenytoin

  1. MOA
  2. Indication
  3. SE
  4. monitoring
A
  1. Na channel blocker
  2. Status epilepticus
    AVOID in absence seizures
  3. 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

  1. Levels after dose change
    CYP450 inducer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Most AEDs are lipid soluble and hepaticacally metabolised. What are the exceptions?

A

Renally excreted: Vigabatrin, gabapentin, levetiracetam (keppra)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

excitatory neuron NT

A

glutamate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

inhibitory neuron NT

A

gaba

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

neuronal transmission

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Drugs with behavioural side effects

A

GABA ethic
Keppra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

AEDS with SE of drowsiness, ataxia, tremor, diplopia, headache

A

Na channel blockers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

RF for idiopathic IC HTN

A
  1. recent weight gain
  2. medications
    Stronger evidence
    • Growth hormone
    • Tetracyclines – e.g. doxycycline
    • Retinoids – e.g. isotretinoin

Weaker evidence
• Thyroxine
• Corticosteroid withdrawal
• Lithium
• Nalidixic acid
• Nitrofurantoin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Idiopathic Benign intracranial hypertension (otherwise known as pseudotumour cerebri)

Definition

Causes

Clinical features

Diagnostic ix

Major risk/cx

Tx

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What AEDs are levels therpaueitcally indicated?

A

Carbemazepine
Phenytoin and phenobarbitone

Both are cyp450 inducers so monitoring levels improves AEs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What common epilepsy syndrome tends to be sleep related/occurring at night or on waking
what phase of sleep is this increased

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What epilepsy syndrome do you see Classic 3Hz spike and wave discharges on EEG
Provoked by hyperventilation

A

Childhood Absence seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

10s profound impairment, abrupt onset/offset
+/- eyelid movement, automatisms

What epilepsy syndrome is this?

What is the typical age group

EEG findings?

Tx?

Prognosis?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the classic presentation of benign epilepsy of childhood and what is the age range affected typically?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What epilepsy syndrome has an EEG with Spikes in occipital region, activated on eye closure and normal background activity

How does it usually present?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What EEG findings are assoc w benign epilepsy of childhood with rolandic spikes?

A

Centrotemporal spikes (Rolandic area)

  • Biphasic, in repetitive bursts
  • Increased in NREM sleep
  • Normal background activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Treatment of Juvenile myoclonic epilepsy

A

Valproate 1st line
- Lifelong tx (excellent response but low rates of remission)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Vigabatrin

MOA

AE

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is this condition?

8yo boy with viral infectino followed by fevers, headache, behaviour change and seizures. MRI shown.

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

SE valproate

A

Weight gain
hair loss
pancreatitis
hepatic failure
embryopathy/teratogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

SE phenobarbitone

A

rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

SE clonazepam

A

incr secretions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Malignant hyperthermia

Cause

Presentation

tx

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Infantile botulism

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

SE vigabatrin

A

weight gain
retinopathy
psychosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

SE topiramate

A

nephrolithiasis
weight loss
acidosis
glaucoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

SE oxcarbazepine

A

hyponatraemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Neural tube defects

What causes them?

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Friedrich’s ataxia

Cause/inheritance

Presentation - (what other organ systems are involved?)

Diagnosis

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Infantile spasms

Typical age of onset

Presentation

EEG findings

Causes

Mx

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Tuberous sclerosis - what is the inheritance pattern/genetics of this condition?

How does this play into management?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is this condition?

How does it present?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Multiple sclerosis (MS)

  • definition
  • RF for MS in kids
  • presentation
  • Ix
  • Tx
A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

fragile x syndrome

inheitance

features

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

DMD vs Becker MD genetics and diagnosis

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

diagnostic criteria NF1

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Features of NF2

  • inheritance
  • diagnostic features
  • presentation
  • management
A

AD

  • more severe than NF1 (NF1 90% of cases, NF2 10% of cases)

Diagnosis req 1 or more of the following:

  1. B/L VIII nerve (vestibulocochlear nerve) acoustic neuromas
  2. Unilateral VIII nerve mass as well as any 2 of: meningioma, neurofibroma, schwannoma, glioma, cataracts
  3. 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

SMA

Genetics/cause
Presentation and age of onset
Types - which is most common and most severe?

Prognosis

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Genetics of SMA

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

SMA tx

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Nusinersin/Spinraza

Indication

MOA

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Viral vector genomes (‘Zolgensma’ = Onasemnogene Abeparvovec
)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Risdiplam

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

causes of neuropathy in children in order of most common

A

CMT
Friedrichs ataxia/SCA
Guillon barre
Neurogeneneration
Leukodystrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Charchot Marię tooth disease

What is it?

Cause, genetics and classification

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Dejerine sottas disease

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Seizure classification

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

DDX for seizure

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Triggers for syncope vs seizures

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

incidence of myoclonus in vasovagal/fainting

A

90% have myoclonus - arhythmic nad multifocal
occasional just a few twitches or symmetric and generalised

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Syncope vs GTCS

  1. precipitating event
  2. falls
  3. convulsions
  4. eyes
  5. hallucinations
  6. incontinence
  7. tongue biting
  8. postictal confusion
A
  1. precipitating event
    - syncope 50%
    - GTCS none
  2. falls
    - syncope flaccid or stiff
    - GTCS stiff
  3. convulsions
    - syncope 80%, usually <30sec, arrhythmic, multi-focal and/or generalised
    - GTCS 1-2 min, rhythmic, generalised
  4. eyes
    - syncope: open, transient upwards or lateral deviation
    - GTCS open, often sustained deviation
  5. hallucinations
    - syncope: late in attack
    - GTCS: may precede seizure in focal epilepsy
  6. incontinence
    - syncope : common
    - GTCS: common
  7. tongue biting
    - syncope: rare
    - GTCS: common
  8. 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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

WEst syndrome

  1. triad of presentation
  2. age onset
  3. most common cause
A

Triad of:

  1. Infantile spasms
    - Clusters of 5-30sec apart
    - Often just after waking
    - Can be flexor, extensor or mixed
    - Can be asymmetric or have focal features
  2. Hypsarrhythmia (EEG) - high amplitude abnormal rhythms
  3. 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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Dravet syndrome

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Doose syndrmoe

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

EEG: paroxysmal 4hz theta bursts, fast generalise spike and poly spike wave, photosensitivity

A

Doose syndrome/epilepsy with myoclonic-atonic seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Causes of epilepsy

A

Structural
Genetic
Infectious
Metabolic
Immune
Unknown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What is the commonest worldwide cause of epilepsy?

A
  • *Neurocysticercosis**
  • parasitic tissue infection caused by larval cysts of the tapeworm Taenia solium
  • causes hippocampal sclerosis
  • tx: praziquantel or albendazole
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Grey matter disorders

What area of brain does this affect
What signs

A

Affecting cortex

Encephalopathy
Seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

White matter disorders

What area of brain does this affect
What signs

A

Affects tracts

Spasticity
Cerebellary signs
Other motor

Progression over time, will eventually affect grey matter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Leucoencephalopathy

what is it?

REd flags for this

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Leukodystrophies

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Metachromatic leukodystrophy (MLD)

Cause/genetics

pREsentation

tx

A

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

69
Q

Adrenoleukodystrophy

Cause/genetics

Presentation

Ix/tx

A

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
70
Q

Zellweger syndrome

Cause

Presentation

Tx/prognosis

A

=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.

71
Q

Alexander disease

A

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

72
Q

Canavan disease

A

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

73
Q

Pelizaeus Merzbacher disease

A

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

74
Q

Niemann pick disease

A

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

75
Q

Tay Sachs disease

A

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

76
Q

Wilson disease

A

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

77
Q

Menckes disease

A

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

78
Q

Rett syndrome

  • inheritance
  • presentation
  • diagnosis
  • prognosis
A

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
79
Q

Neuronal ceroid lipofuscinosis/batten disease

Presentation

A

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

80
Q

Features of mitochondrial disorders

A

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
81
Q

Tics

Definition

Causes - prim vs sec

Tx

A
  • 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

  1. idiopathic
    - transient (<12mo)
    - chronic (>12mo)
    - Tourette syndrome (waxing and waning motor and verbal tics > 12mo)
  2. secondary (rare)
    - sydenham chorea
    - post HIE
    - medications

Treatment

  • Education
  • Clonidine
  • Risperidone
  • Behavioural treatments
  • Treat comorbidities (ADHD w stimulant, OCD, anxiety w SSRI)
82
Q

Stereotypies

A
  • 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)
83
Q

Dystonia

A

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
84
Q

Dystonia vs spasticity

A

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)

85
Q

Causes of dystonia

A

Benign/transient
- Benign paroxysmal torticollis of infancy

Acquired or secondary to innjury

  • term HIE
  • kernicterus
  • metabolic conditions
  • neurodegen conditions

Genetic forms

86
Q

Treatments for dystonia

A

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

87
Q

Myoclonus

A

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
88
Q

Tremor

A

Oscillating, rhythmic, involuntary
Usually single joint/fixed point but can also be an axis

Causes

  • physiologic
  • Metabolic
  • Medicaitons
  • thyroid
89
Q

Chorea

A

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
90
Q

Dyskinesia

A
  • Nonspecific term describing an excess of movement
  • Sudden abnormal movements that happen episodically

3 types:

  1. paroxysmal kinesigenic dyskinesia: short duration frequent events, triggered by specific movements
  2. paroxysmal non-kinesigenic dyskinesia: infrequent but may last hours-days
  3. paroxysmal exercise induced dyskinesia: after several minutes of activity/exercise
91
Q

Neuroaxis and what signs does a lesion produce?

  • Upper Motor Neurons
  • Lower Motor Neurons
  • Cerebellum
A

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
92
Q

Floppy baby - weak vs strong
causes

A

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
93
Q

Clues to a central cause for floppy baby

A
  • 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)
94
Q

Clues to a peripheral cause for floppy baby

A

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
95
Q

Conditions in which CK is elevated

A
  • Muscular dystrophies (markedly elevated, >1000)
    • DMD
    • Myotonic dystrophy
  • Myopathies (normal to 300s)
  • SMA (normal or mildly elevated)
  • Pompe disease (glycogen storage disorder type II)
96
Q

ix for floppy baby

A

CK level
Nerve conduction and EMG
Muscle biopsy

97
Q

DMD muscle bx features

A
  • Abnormally shaped muscle cells
  • Fatty infiltration
  • Nuclei are central rather than peripherally located within muscle cell
98
Q

what condition is a triplet repeat disorder

A

myotonic dystrophy

freidrich ataxia

99
Q

Disorders of the anterior horn cell

A
  • SMA (spinal muscular atrophy)
  • non 5q sma
  • polio
  • enterioviral infections
  • Hopkins’ syndrome
  • ALS (motor neuron disease)
100
Q

Non-5q SMAs

A

Spinal muscular atrophy with resp distress
Riboflavin transporter deficiency neuronopathy - responsive to riboflavin

101
Q

SMA investigation results

CK
NCS
EMG
Repetitive nerve stimulation
Genetics

A

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

102
Q

Guillan Barre syndrome

clinical features

complications

Ix

DDX

Tx

Prognosis

A

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%
  1. 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
103
Q

Chronic inflammation demyelinating polyneuropathy CIDP

A

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
104
Q

CSF passage

A

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)

105
Q

Hydrocephalus causes

A
  • 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
106
Q

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

A

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)

107
Q

What nerve is commonly affected in raised ICP

A

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

108
Q

Ddx for ring enhancing lesions on CTB

A

Tumour
Abscess

109
Q

Causes of cerebral abscesses

A
  • 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

110
Q

EEG basics

A

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

111
Q

First line Treatment for most epilepsies (and exceptions)

A

valproate

112
Q

treatment juvenile absence epilepsy

A

Ethosuximide is first line

Sodium valproate or lamotrigine

113
Q

treatment infantile spasm

A

Steroids

vigabatrin

114
Q

Treatment benign rolandic epilepsy

A

Nothing
Low dose CBZ

115
Q

Treatment symptomatic focal epilepsy in infants

A

phenobarbitone

116
Q

treatment for symptomatic focal seizure (temporal lobe or frontal lobe epilepsies)

A

carbamazepine

117
Q

Which anticonvulsant isn’t teratogenic

A

lamotrigine

118
Q

A 6yo child wakes from sleep with involuntary mouth movements and unable to speak. He subsequently has a GTCS

A

Benign rolandic epilepsy

119
Q

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

A

Dravet syndrome

120
Q

A 7 month old child presents with epileptic spasms occurring in clusters, mainly on waking. She has hypsarrhythmia on EEG.

A

infantile spasms

121
Q

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.

A

childhood Absence epilepsy

122
Q

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 .

A

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:

  1. Multiple generalized seizure types
  2. A slow spike-and-wave pattern (less than 2.5 Hz) on EEG
  3. Cognitive dysfunction.
123
Q

Nerve supply to urethra/genitalia/anus

A

Pudendal nerve S2-4

124
Q

How is the perineal nerve generally injured?

vs L5 nerve root injury?

A

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
125
Q

Optic neuritis

What is it
Causes
Presentation

A

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

126
Q

What is the main difference between Beckers and Duchennes muscular dystrophy

A

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
127
Q

What is this condition?

How might they present?

A

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
128
Q

Band heterotopia

A

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

129
Q

Schizencephaly

A

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

130
Q

What syndrome?

  1. Developmental delay + intellectual disability
  2. Self-injurious behavior – bite lips
  3. Movement disorder
  4. Hyperuricaemia
A

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.
131
Q

NF type 1 features

A

Type 1

  1. Cutaneous = café au lait macules, axillary or inguinal freckling
  2. Eyes = Lisch nodules
  3. Tumours = peripheral neurofibromas (neurofibroma, plexiform), optic pathway glioma, CNS neoplasms, other sarcomas
  4. Bone abnormalities = long bone dysplasia, pseudoarthrosis, short stature, scoliosis
  5. Neurological = cognitive, autism, seizures
  6. Hypertension
132
Q

NF Type 2 features

A

Type 2

  1. Vestibular schwannomas – bilateral
  2. Meningioma
  3. Schwannoma at other locations
  4. Glioma
  5. Neurofibroma
  6. Posterior subcapsular lenticular opacity
133
Q

What syndrome/disease?

  1. Spinal or cerebellar haemangioblastoma
  2. Retinal angiomata
  3. Cystic lesions of kidney/pancreas/iver/epididymis
  4. Renal carcinoma – results in death
A

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)

134
Q

What syndrome/disease?

  1. Neuropathic limb pain
  2. Telangiectasias and angiokeratomas
  3. Corneal opacities
  4. Renal manifestations
A

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.

135
Q

Features of tuberous sclerosis

A
  1. Eyes = multiple retinal lesions (hamartomas; rarely affect vision)
  2. 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
  1. 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
  1. 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
136
Q

What is a hemiplegic migraine?

Triggers
Treatment

A
  • 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
137
Q

What AED medications are relatively CI in childhood absence epilepsy

A

avoid carbamazepine, gabapentin, vigabatrin and tigabine as aggravate seizures

138
Q

Features of simple vs complex febrile seizures

A

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

139
Q

Risk of epilepsy following febrile seizure

A

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%.

140
Q

Congenital Myotonic dystrophy

  • what is it/genetics
  • presentation
  • diagnosis
  • mx
A

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

141
Q

what conditions does the NST detect?

A
  • Cystic fibrosis
  • Fatty acid oxidation defects
  • organic academias
  • amino acidaemias
  • maternal B12 deficiency
  • congenital hypothyroidism (incr TSH)
142
Q

Management of raised ICP

  • acute vs chronic
A

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
    *
143
Q

Causes of intracranial calcification

A
  • 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
144
Q

Cranial nerves

A
  1. Olfactory - smell
  2. Optic - vision
  3. Oculomotor - all EOM except superior oblique and lateral rectus
  4. Trochlear - Superior oblique (intorsion)
  5. Trigeminal - Massetor muscles and sensation to face and taste ant 2/3 tongue
    1. V1 - opthalmic branch
    2. V2 - maxillary branch
    3. V3 - mandibular branch
  6. Abducens - lateral rectus
  7. Facial - Facial muscles, submand/subling/lacrimal glands, taste to posterior 1/3 tongue
  8. Vestbulocochlear - hearing nad balance
  9. Glossopharyngeal - Parotid gland; gag afferent, sensation to pharynx
  10. Vagus - Gag efferent, vagal stuff
  11. Accessory - Sternomastoid, trapezius muscles
  12. Hypoglossal - tongue musclecs
145
Q

Types of craniosynostoses and resulting cranial deformities

A
146
Q

Causes of premature vs delayed closure of fontanelles

A

Premature closure

  • Hyperthyroid
  • Craniosynostosis
  • Microcephaly

Delayed closure

  • Hypothyroid
  • Malnutritin
  • Rickets
  • Hydrocephalus
  • Osteogenesis imperfecta
  • Down syndrome/T13 other syndrome
147
Q

Spina bifida

What is it/what causes it

What sx/signs might you appreciate

A

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
148
Q

Lissencephaly

  • Type 1 vs Type 2
A

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
149
Q

Types of CP

A

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

150
Q

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

A

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
151
Q

What is this condition?

5 year old male with normal development until sudden abrupt deterioration in speech -> mutism

And seizures (partial or generalised)

A

Lendau-Kleffner syndrome

152
Q

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?

A

Batten disease (Ceroid lipofiscinosis)

  • Vision loss = retinitis pigmentosa
  • AR condition
153
Q

Main cause of CP

A
  • 80% Antenatal insult (congenital infection, cerebral dysgenesis or malformation)
  • 10% Intrapartum (HIE)
  • 10% PN (IVH, hydrocephalus, head trauyma NAI, kernicterus, cerebral ischaeemia etc)
154
Q

Transverse myelitis

  • What is it?
  • Causes
  • Presentation
  • Tx/prognosis
A
  • 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
155
Q

Myasthenia Gravis

Ix, what ab are assoc?

Presentation

Mx

What is the risk to babies born to mothers w MG?

A

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
156
Q

What is the most severe form of congenital muscular dystrophy?

what is it caused by?

A

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
157
Q

Diagnosis?

Infantile hypotonia progressing to ataxia

Developmental delay

MRIB:

A

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

158
Q

MELAS

A

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.

159
Q

Triad of features in sydenham’s chorea?

A
  1. Chorea and dysarthria
  2. Emotional lability (also OCD/psych illnesses assoc)
  3. Hypotonia
    1. 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.
160
Q

Stroke management

A

• 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

161
Q
A
162
Q

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?

A

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)
163
Q

Role of streoids in treatment of MOG vs AQP4 Ab assoc disease (Optic Neuritis /Neuromyelitis optica spectrum disorder/ADEM)

A

MOG assoc is more responsive than AQP4 Ab disease

Longer steroid tail wean with MOG assoc disease due to higher risk of relapse

164
Q

Opsoclonus myoclonus

Ataxia

Irritable child

Age 1-3yo

What is this condition and what are the causes and ix findings?

A

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

165
Q

GQ1B antibodies are assoc w which neuro conditions?

A

Bickerstaff encephalitis - triad:

  1. Ataxia
  2. Opthalmoparesis (subacute onset over ~1 week)
  3. Encephalitis
  4. BRISK reflexes.

Miller Fischer syndrome - triad:

  1. Opthalmoplegia
  2. Ataxia
  3. Areflexia with PROXIMAL muscle weakness

Both rare variants of GBS

166
Q

What infection is associated with GBS?

A

Campylobacter

167
Q

What vitamin deficiency is associated with MS?

A

vitamin D deficiency

168
Q

Distribution of weakness of

  1. CMT
  2. SMA II
  3. Congential myopathy
  4. SMA III
  5. LGMD (duchennes)
  6. FSHD
A
  1. CMT - distal
  2. SMA II - generalised, tongue fasciculations
  3. Congential myopathy - generalised
  4. SMA III - proximal
  5. LGMD (duchennes) - proximal, will have scapular winging and gower’s sign and waddling gait
  6. FSHD - shoulders, face, outer calves

FRACP (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions