Paediatric Neurology Update 2014

Gina O’Grady

Neurology Fellow

Infantile spasms

Infantile onset epilepsy

~ 1 in 2250 infants

Onset usually 3-8 months

Manifestations

Brief symmetrical contractions of

musculature of the neck, trunk (axial)

and extremities lasting up to 5s

Commonly occur in clusters

Flexor/extensor or mixed

http://www.youtube.com/watch?v=kqp9LGlULxI

http://www.youtube.com/watch?v=aVoJtslvqOU

http://www.youtube.com/watch?v=hK3vkHcSb6Y

http://www.youtube.com/watch?v=HC4p7eTez1w

Manifestations

Developmental regression

Particularly if diagnosis is delayed

70-85% have delayed development

prior to the onset of spasms

Early recognition is crucial

Low threshold of suspicion

Repetitive/clustered events are a clue

Video is always helpful

Referral for urgent EEG/assessment

EEG Hypsarrhythmia – chaotic, disorganised, high

amplitude spike and slow wave activity

West syndrome

Epileptic spasms

Neurodevelopmental regression

EEG finding of hypsarrhythmia

When all three are present the eponym “West syndrome” is sometimes used

Named after English physician William

West, who published in The Lancet in 1841

describing his own son

Aetiology

“Symptomatic” - 60-70%

Have an underlying disorder identified

“Cryptogenic” - 10-40%

No underlying cause identified

May have a better prognosis

Aetiology

Structural Hypoxic ischaemic encephalopathy

Perinatal stroke

Periventricular leukomalacia

Periventricular haemorrhage

Malformation – brain malformation or focal cortical dysplasia

Genetic Neurocutaneous syndromes e.g. Tuberous

sclerosis, NF1, Sturge-Weber

Chromosomal anomalies – Down syndrome

ARX, CDKL5, FOXG1, GRIN1, GRIN2A, STXBP1

Aetiology

Metabolic

Phenyketonuria

Non-ketotic hyperglycinaemia

Leigh disease

Pyridoxine responsive epilepsy

Biotinidase deficiency

Infection

Congenital infection especially CMV

Tuberous sclerosis

7% of infants in the UK Infantile Spasms

Study

Tuberous sclerosis

Pellock et al. Infantile spasms: A U.S. consensus

report. Epilepsia. 2010 Jul 1;51(10):2175–89.

Investigations

EEG

MRI

Metabolic work up Urine metabolic screen, newborn screen,

vitamin B12, biotinidase, urine P6C, lactate, ammonia, CSF studies (lactate, protein, glucose, NTs, amino acids), serum amino acids, transferrin isoforms

CGH array

Congenital infection screen.

Ophthalmology review

Steroid therapy

UKISS - United Kingdom Infantile Spasm Study 10mg prednisolone QID – 2 weeks ○ If spasms continue on Day 7 or reappear

between Day 8 and Day 14 inclusive, increase the dose to 20 mg three times a day for the remaining doses

Followed by a tapering course

Prednisolone vs ACTH

UKISS United Kingdom Infantile Spasm Study

150 hospitals ; 107 infants with IS (excluding TSC)

Prednisolone or ACTH depot (n=55) vs vigabatrin (n=52)

Primary outcome – cessation of spasms by day 13 and 14:

Better initial control of spasms in infants allocated

hormonal treatment than in those allocated vigabatrin,

regardless of etiology (Lux 2004).

40/55 (73%) of infants assigned hormonal treatments

[prednisolone 21/30 [70%], tetracosactide 19/25 [76%]] vs

28 (54%) of 52 infants assigned vigabatrin

UKISS United Kingdom Infantile Spasm Study

14mo and 4 year (n=77) follow up

Nine of 107 infants had died.

Longer lead time to treatment associated with worse

neurodevelomental outcome

In the subgroup of infants with no identified aetiology,

development remained better in those allocated

hormonal treatment

Alternatives to steroids

Infants with Tuberous sclerosis – Vigabatrin

Nitrazepam

Ketogenic diet

Monitoring

Surveillance for steroid side effects

EEG surveillance

Monitoring for spasm/seizure

recurrence

Spasm relapse

Steroids

Vigabatrin

Nitrazepam

Topiramate

Vigabatrin

Risk of visual field constriction and

retinal toxicity ○ 1/3rd of children aged 9-19 years

○ Lower risk with short-term use

Abnormal MRI signal intensity in the

thalamus, basal ganglia, dentate

nucleus and brainstem – reversible

Pyridoxine

The possibility of pyridoxine dependent seizures should be considered although IS are not typical

Consider in those infants: with additional seizure types, and

where no other cause for their spasms is known.

Outcome

Abnormal development in >85%

Mental retardation

Autistic spectrum disorder

Refractory epilepsy

Other seizure types – >60%

Lennox-Gastaut syndrome – 40%

Neurodevelopmental follow up

Early treatment is associated with a better

neurodevelopmental outcome

UKISS – longer lead time to treatment

associated with a worse

neurodevelopmental outcome at 4

years.

Erroneous diagnoses

Gastroesophageal reflux

Constipation

Colitis

Differential diagnoses

Benign Infantile Shuddering http://www.youtube.com/watch?v=3kFcWh3yfKo

http://www.youtube.com/watch?v=fuuysAn5QDc&list=PLA3DB0838DC651F57&index=5

Benign sleep myoclonus

Conclusion

Early diagnosis

Low index of suspicion

Urgent referral

Early commencement of therapy

References

Go CY et al. Evidence-based guideline update: Medical

treatment of infantile spasms: Report of the Guideline

Development Subcommittee of the American Academy of

Neurology and the Practice Committee of the Child

Neurology Society. Neurology. 2012 Jun 11;78(24):1974–80.

Lux AL et al. The United Kingdom Infantile Spasms Study

comparing vigabatrin with prednisolone or tetracosactide at

14 days: a multicentre, randomised controlled trial. Lancet.

2004 Nov;364(9447):1773–8.

Pellock JM et al. Infantile spasms: A U.S. consensus report.

Epilepsia. 2010 Jul 1;51(10):2175–89.