Update on paediatric neurology

Practical Paediatrics, June 2016

Dr Margaret KaminskaConsultant in Paediatric Neurology and NeurodisabilityComplex Motor Disorders Service

Evelina Children’s Hospital

Outline:Neurological examinationMovement disorders

examples and etiologymanagementstatus dystonicus

EpilepsyWhen to refer seizures/epilepsy

Autoimmune encephalitis

Neurological examination• Observation

– Play in waiting area

– Walking into clinic

– Facial features

– Posture

– Movements

– Speech and cognition

– Visual behaviour

– Abnormal movements, events

Neurological examination

• Fun and Games (screening)

– Standing up (chair or floor)

– Arms out

– Eyes closed

– Standing on one leg

– Hopping, skipping

– Walking on tip toes, heels, tandem walking

– Climb onto couch

Neurological examination

• Targeted formal examination– Tone (trunk and limbs)– Power (full antigravity = 3/5)– Reflexes– Cranial nerves (vision, eye movements, facial

asymmetry, swallowing diffculty, cough)– Sensation– Measurements

• Weight, height, head circumference

– Extras • Heart, abdomen, spine, hips etc

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Movement disorders

Movement disorders in children and young people

Hyperkinetic

• Tics• Tremor• Chorea• Athetosis• Dystonia• Mioclonus • Stereotypies

Hypertonic

• Spasticity• Dystonia • Rigidity

Negative signs

weakness

Reduced selective motor control

Ataxia

Apraxia

Sanger TD, Chen D et al: Definition and classification of hyperkinetic movements in childhood; Mov Disord. 2010 Aug

Sanger TD, Delgado L et al: Classification and definition of disorders causing hypertonia in childhood; Paediatrics 2003 Jan

Sanger TD, Chen D et al: Definitions and classification of negative motor signs in childhood; Paediatrics 2006

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Movement disorder can be interpreted as seizures and should be carefully differentiated!

34 children with CP: 87% had spasticity78 % had dystonia

2009

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Gait:

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Spasticity:•Velocity dependant increase of tone•Brisk jerks•Sustained ankle clonus•weakness

Dystonia

Dystonia: involuntary continuous or intermittent muscle spasms causing repeated twisting movements or postures or both.Tone not velocity dependant, jerks normal or can be absent

“Not to fast – not too slow, not to small- not too big, not too strong – not too weak”

Myoclonus

myoclonus:

arrhythmic, short, shock-like movements caused by sudden muscle spasm or relaxation

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Chorea

Tremor

Tremor: rhytmic movements around a joint

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Tremor

What is unusual?

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• Structural brain damage– cerebral palsies

– Childhood strokes

– Encephalitis –infective/autoimmune

– Tumours

– Acquired brain injury (traumatic, hypoxic)

• Metabolic and degenerative disorders

• Other – Infection, vascular malformations,

– Genetic: Rett syndrome, DYT1, DYT11, TITF1, other genetic movement disorders

– Toxic: medication, CO

• All deserve detailed investigations

• Brain scans, blood and urine tests, genetic tests

Investigations for movement disorders –tailored to suspected aetiology

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Treatment options for a child with movement disorder

• Treatment of underlying aetiology if possible

• Treat exacerbating factors – feeding problems, reflux, pain, anxiety

• Nutrition

• Positioning

• Avoid physical restraint

• Medical treatment of tone, movement disorder

Spasticity

Baclofen

Benzodiazepines

Tizanidine

Dantrolene

Botulinum toxin

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Medication for spasticity and dystonia

DystoniaBaclofenTrihexyphenidyl vs procyclidineBenzodiazepinesL-dopaTetrabenazineTizanidineClonidineChloral hydrateGabapentinCarbamazepineDantroleneBotulinum toxin

Intrathecal baclofen pump

Deep Brain Stimulation

Intrathecal baclofen pump

Always think about goals for treatment!

Selective dorsal rhizotomy

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Status dystonicus

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Status dystonicus: case vignette

9y boy with quadriplegic CP, ex-prem, PEG1 day Hx pf fever 38.5Distressed, unsettled, increased movementsIncreased respiratory secretions

? Chest infection : CRP 9, WBC 11, Chest X-Ray – possible peri-bronchial changes in right lower lobe, urine clearUrea 7.4, normal electrolytes and creatinine

Started treatment with co-amoxiclav

Day 3 – continues to spike fever up to 39.5 at times, unsettledChest X-Ray reviewed – no convincing signs of chest infectioninflammatory markers lowmum says – sleeps very little, how much? Not documented

CK 60 000 urea 8.5 normal electrolytes creatinine – upper normal range

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Status dystonicus: definition

Life threatening movement disorder emergencyIncreasingly frequent or continuous severe episodes of generalized dystonic spasms (contractions)

Status dystonicus: Tonic – mainly sustained contractures and postures Phasic – rapid and repetitive dystonic contractions

Considered rare – only 100 reported cases, but likely underreported and underrecognised

Up to 60% between ages 5 and 16 years

Cerebral palsy – most common cause of secondary dystonia in children

Allen et al 2013

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Status dystonicus: dystonia severity grades

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Status dystonicus: management plan

Allen et al 2013

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Status dystonicus: management plan

Consider if increased stiffness, movements, irritability, poor sleep, fever Check CK, electrolytes, urea, creatinine, liver, Ca, Mg, P, BGLook for contributing factors and treat– infection, pain (otitis, fracture , gut), ITB or DBS

malfunction.Talk to your paediatric neurology team

Maintain feeding if possibleEnsure good hydration enteral/IV– monitor urine output, fluid chart, renal function tests,

BG as required, CK, urine dipstick for blood (myoglobinuria)Sleep chart to clearly document periods of sleepExtreme spasms, discomfort particularly if airway compromise – IV lorazepam/PR diazepam

or buccal midazolam as temporizing measure“sleep abolishes dystonia”

chloral hydrate 30-50mg/kg as required up to 4-6 hourlyclonidine first dose 1mcg/kg and repeat 4-6-8 hourly

every next dose can be increased by 1mcg/kg up tp 25mcg if response unsatisfactorydoses up to 2mcg/kg/hour IV or enteral. Monitor BP and HR.

Consider midazolam infusion but tolerance develops quickly.

Clonidine

Dystonia treatmentSpinal and supraspinal α 2 adrenergic receptor agonistReduces aspartate and glutamate release in presynaptic

terminals anitinocioceptive properties

Initially used for treatment of arterial hypertensionSide effects : somnolence, bradycardia, low BPSame oral/transdermal and IV daily dose

Clonidine - our experience

• 1 mcg /kg test dose - monitor BP

• 3 – 8 doses or continuous IV infusion

• Max dose used in our group:

3-4 mcg/kg/hour enteral and

48 mcg/kg/day (2mcg/kg/hour) IV

• Side effects at high doses (in combination with chloral hydrate):

•

Chloral hydrate

Sedative and hypnotic through enhancing GABA receptorsIngredient of Mickey FinnMetabolizes to tri-chloro-ethanol

Dose: 30-50 mg/kg or 100mg/kg/24h in 3-4doses, max 4g/24h

Side effects: deep sedation, respiratory depression, low bloodpressure, liver failure, tolerance, dependency, withdrawalsymptoms

James Bond says, "that's...chloral hydrate" in the movie "The Living Daylights" before collapsing from it's effects

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EpilepsyWhen to refer?

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Case study 4/12 boy

• Term delivery, IUGR, thrombocytopenia resolved

• New onset of focal seizures: eyes deviation and flickering +/- upper

limb jerks

• Seizures stopped after phenytoin load

• Normal CT, baseline bloods and LP

• Refer to neurology? Y N

• Clinic or on call service?

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InfantsAbnormal imagingFocal onset seizuresContinuing seizures following trials of 2

AEDs (refractory epilepsy)Possible neuro-degenerationUncertainties re diagnosisOngoing ? Non-epileptic events

Neurology referralKnow your service and pathway!

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Case study: 18/12 girl

Ex prem 29/40

Neonatal sepsis, early seizures

Developmental delay

Evolving motor disorder – tone mostly increased in left UL, brisk DTR

Meds: valproate + phenobarbiton

Mum reports episodes of stiffness with glazed look

Valproate increased

trihexyphenidyl started – some improvement

EEG normal

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18/12 girl, ex prem - home videoMedication: Na valproate, phenobarbiton, trihexyphenidyl

• Was it epileptic?

infant toddler Older child

Normal movements

‘Shuddering attacks’

Rigors

Sleep myoclonus

Gratification disorder

Gastro-oesophageal

reflux

Movement disorder

(eg paroxysmal tonic

upgaze)

Cardiac arrhythmia

BehaviouralBreath holdingNight terrorsGratification disorderStereotypiesDay-dreamingLearning Diffs

MigraineSyncopeCardiacBenign paroxysmal vertigoMovement disorder Fabricated illness

Tic disorderCardiacVaso-vagal syncope

Movement disorder

Pseudo-seizures/non epileptic attacks

Paediatric Epilepsy Training

• Standardised courses

• Available in all regions

• PET 1

• PET 2

• PET 3

www.bpna.org.uk/pet

Encephalitis

Autoimmune encephalitis

Case: 5 year old girl

• Intermittent slurred speech 3 days after minor head injury

• Normal brain MRI

• Within next few days: progressive episodes of confusion and behavioural change

• Chorea of the left hand

Case: 5y old girl

• Few focal seizures

• Speech problems worsen to no speech

• chorea one hand persists

• EEG encephalopathic

• CSF – normal cells, sugar and protein

• Viral serology and cultures negative

• Rx: antibiotics, antivirals, phenytoin

Case: 5y old girl

• NMDA receptor antibody positive

• High dose steroids

• Full recovery at 12 months FU

Auto-immune encephalitides

• Treatable cause of encephalitis• Neuropsychiatric features very common:

behavioural change 63%confusion 50%hallucinations 25%Seizures 83% and movement disorder 38%

Hacohen et al 2013 • Auto-antibodies to cell surface antigens, crucial for

neurotransmission• VGKC, GAD, NMDA receptor antibodies . . .• >400 cases clinically relevant elevated titres in UK over last 3

years• Increasingly diagnosed in children

still under diagnosed• Paraneoplastic – much more frequent in adults

NMDA encephalitis

• Short history – days/weeks

• Seizures/odd episodes

• Behavioural change, encephalopathy

• Involuntary movements

• EEG abnormal, lymphocytes in CSF, +/- imaging abnormalities

• NMDA receptor antibody positive

• N-methyl-D-aspartate glutamate voltage-dependent channels

• Association with ovarian teratoma and other neoplasia (20-50% adults)

VGKC encephalitis

• Can present as limbic encephalitis, but other presentations possible

• Subacute personality change, memory problems, seizures within first few days; temporal lobe epilepsy

• MRI changes – high signal medial temporal lobe often with contrast enhancement

• Association with malignancy

(adults; recent UK study – 39 children VGKC Ab+, none had neoplasm; presented at BPNA conference 2014)

• often monophasic illness

• Antibody titres fall with treatment

Auto-immune encephalitisearly treatment

• Byrne et al, 2014:

NMDAR encephalitis, literature review, 43 cases

88% treated within 15 days had full recovery36% treated after 15 days had full recovery

Treatment: steroids, IVIG, plasma exchange, rituximab

Autoimmune encephalitis – diagnostic criteriaZuliani et al 2012

Criteria•Acute or subacute (<12 weeks) onset of symptoms

•Evidence of CNS inflammation (at least one of):

CSF (lymphocytic pleocytosis, CSF specific oligoclonal bands or elevated

IgG index)

MRI inflammatory changes

Inflammatory neuropathology on biopsy

•Exclusion of other causes (infective, trauma, toxic, metabolic, tumors,

demyelinating or history of previous CNS disease

Supportive features• History of other autoimmune disorder

• Preceding infectious illness or viral-disease-like prodromes

Dr Margaret KaminskaPractical Paediatrics, June 2016