Epilepsy and Movement Disorders in Rett Syndrome

Daniel E Lumsden

Consultant Paediatric Neurologist

Honorary Clinical Senior Lecturer

What do we mean when we talk about “Epilepsy”?

What do we mean when we talk about “Movement Disorders”?

Why is this important for Rett Syndrome?

Outline

Breathing

Disturbances

Epilepsy

Movement

Disorder

Emotion/

Anxiety

Epilepsy

Movement

Disorder

Different Abnormal

MovementsDifferent Causes

Different

Treatments

Epilepsy

“A Paroxysmal

discharge of cerebral

neurones sufficient to

cause a

subjective/objective

change in behaviour

(Stephenson 1990)”

A tendency to have

unprovoked seizures

‘..his neck turns left, his hands and feet are tense

and his eyes wide open, and from his mouth

froth is flowing without having any

consciousness”

Mesopotamian description

Epilepsy is a

problem with the

surface of the

brain (cortex)

Movement disorders

are problems with the

deeper brain structure

Epilepsy in Rett Syndrome

Rett Syndrome Natural History study (2006 to 2015)

1205 participants (922 typical RS)

Point prevalence of active seizures 30-44%

Life time risk estimated almost 90%

Risk of epilepsy related to more severe phenotype rather then MECP2

genotype

Seizure freedom was seen in a small number with history of epilepsy

12% of ”seizures” described by parent not seizures

Tarquinio et al 2017

Tarquinio et al 2017

Tarquinio et al 2017

There is not one type of seizure or Type of Epilepsy Which is “typical”

for RS

Children and Young People with RS can experience pretty much any

seizure type

Treatment of Epilepsy in RS

Guided by the seizure type, EEG and other symptoms

No RS specific treatments

No RCT in RS

Commonly used AED:

Sodium valproate, lamotrigine, levetiracetam, topirimate,

carbamazepine,

Caution with benzodiazepines and phenobarbitone due to sedative

effect

Movement

Disorder

Clinical syndromes with either

an excess of movement or a

paucity of voluntary and

involuntary movements,

unrelated to weakness or

spasticity

Hyperkinetic Movement Disorders

(HMD) in Children

Dystonia Chorea Myoclonus Tics

What do we know about Movement Disorders in Rett

Syndrome

Fitzgerald et al 1990

Movement Disorder Number of Cases

Stereotypy 32/32 (100%)

Bruxism 31/32 (97%)

Oculogyric Crisis 20/32 (63%)

Dystonia 19/32 (59%)

Scoliosis 16/32 (50%)

Myoclonus 11/32 (34%)

Athetosis 4/32 (12.5%)

Hypomimia 20/32 (63%)

Rigidity 14/32 (44%)

Hypokinesia 13/32 (41%)

Data from Temudo et al

<60 months post-regression >60 months post-regression

Movement

Problem

Missence Truncating Missence Truncating

Stereotypies 100 100 100 100

Dystonia 22.2 50 58.8 95

Rigidity 22.2 64.3 41.2 55

Tremor 55.6 42.9 47.1 50

Ataxia 44.2 42.9 47.1 15.0

Hand Stereotypies in Rett Syndrome

Repetitive, simple movements that can

be voluntarily suppressed

©2007 American Academy of Neurology. Published by LWW_American Academy of Neurology. 2

Temudo et L

2007

Do Hand Stereotypies vary with and without MECP2 mutations?

Temudo et al 2007

83 patients with Rett Syndrome (53 with MECP2 mutations)

No difference in midline stereotypies between groups

Patients with MECP2 mutations more varied HS

Hair pulling HS more common with MECP2 mutation

Number of stereotypies seemed to decrease with age

Hand Stereotypies in the Australian Database

Carter et al 2009

143 cases

60% midline wringing

Median 2 stereotypies, decreased with age

Clapping and mouthing more prevalent < 8 years

Wringing more prevalent > 19 years

Limited relationship to MECP2 mutation

Hand Stereotypies:

Rett Syndrome versus Autism Disorder

Wong et al 2012

20 children RS, 20 children Autism Disorder

RS – Predominantly complex, continuous, midline and involving

mouthing

AD – Simple, bilateral, intermittent and involving objects

Do Hand Stereotypies vary between Typical and Atypical Rett

Syndrome?

Wong et al 2017

43 Typical RS, 15 Atypical RS

More varied hand stereotypies in Atypical RS

Ringing commonest HS in Typical RS (58.1%)

Flapping commonest HS in Atypical RS (73.3%)

? Decrease >10 years of age

Hand Stereotypies

Dystonia/Rigidity

Proportion of

RS

Increasing Age

Change in Movement Disorder in Rett Syndrome with

Age

Hand Stereotypies

Dystonia

Treating Movement Disorders

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

“THE POO CYCLE”

Dystonia

Worsens

More

Medication

Given

Gut Motility

Slows

Constipation

Becomes

More

Painful

Why Treat Movement Disorders in RS

Medications very significant side effects, so very important to have clear

rationale for treatment, as well as some way of measuring if desired

outcome has been achieved:

• Painful/Distressing

• Disabling

• Interfere with care

• Musculoskeletal deformity

• Respiratory compromise

Need to consider what metric to judge success

Avoid

Triggering

Factors

Treat

Triggers

Directly

Treat

Movement

Good pressure/skin

care

Good sleep hygiene

Nutrition/varied diet

Vaccination

Emotional/Psychological

support

Choice of medication

Depends upon:

Background meds

Urgency of treatment

Other aspects of

Motor Disorder etc

Analgesia

Laxatives

Relieve urinary retention

Orthopaedic input

Antibiotics

How much do we know about Epilepsy and Movement Disorders

in Rett Syndrome

Pubmed search results

“Rett Syndrome” = 3347

“Rett Syndrome” AND “Epilepsy” = 345

“Rett Syndrome” AND “stereotypy” = 160

“Rett Syndrome” AND “Dystonia” = 38

Is it always easy to tell if a movement is a Seizure

Or a Movement Disorder?

Discriminating between Seizures and Movement

Disorders

• Get a description

• Get a video

• Get an EEG

• Get a longer EEG

Conclusions

Epilepsy very common in RS, and runs a varied clinical course

No RS specific epilepsy

Movement Disorder almost universal in RS (hand stereotypies)

Hand stereotypies appear to reduce with age, whilst dystonia and

rigidity become more prevalent

No RS specific evidence based guidance for management of either

epilepsy or movement disorders

Multimodal management important, with a clear view of the goal of

intervention