Intrathecal baclofen in children and adolescents with cerebral palsy

Dr Ram KumarConsultant Paediatric Neurologist

Alder Hey, LiverpoolMay 2012

Summary

• Case example: before and after ITB (short term effects)

• Refresher on ITB and basics• Another couple of case examples

demonstrating context of ITB use in teenagers with CP

• Other issues particularly pain• Useful references

• Case A: seen March 2011• 15• HIE Grade 2 or 3• Athetoid dystonic 4 limb cerebral palsy• GMFCS Level 5; MACS 4• Good cognition, dysarthria• Minimal co-morbidities• Increasing dystonia• Previous hip surgery – pseudoarthrosis on left• Spine X-ray pre-ITB (6 months): 51 deg Cobb angle

Case A: Supine spine x-ray 51 deg Cobb angle

Previous adductor tenotomies, botulinum toxin lower limbs, bilateral hip reconstruction surgery

Progress

• Main goals: voluntary upper limb control, pain relief, improve flexibility of spinal curvature

• ITB test dose November 2011 – successful; low pressure headache

• Proceed to ITB implantation Feb 2012• Current dose ITB 180 mcg/day

?

Refresher on ITBTitanium40 ml capacity175 g8.8 cm diameter7 year life except at high infusion rates

ConnectorOpaque one-piece catheter89 cm long; internal volume ~ 1 day’s worth of infusion

Refill through the central port

Programmer and wand

Various ways of programming infusion e.g. simple continuous, variable rate continuous, complex bolus dosing regime

Intrathecal baclofen itself

• ITB provides 1000 times the CSF concentration compared to oral baclofen

• Rule of thumb 100mg/day of oral baclofen = 100mcg/day

• Acts on GABA-B receptor – but where?• Volume and flow effects of IT baclofen• Receptor downregulation and tolerance• Overdose and withdrawal effects life-threatening

IT baclofen• Concentration of 1000mcg/ml to 4000mcg/ml• With 40ml pump reservoir, minimum volume of 3

mls• 1000mcg/ml solution at 250mcg/day. Would

need refill every 4.5 months• Alarm for low reservoir volume and nearing end

of life• Can be removed – not permanent procedure• Implications: 100% commitment and ability to

attend clinics

Usual process of assessment

Consensus on the appropriate use of ITB in paediatric spasticity. Eur J Paed Neurol 2009

Diagnosis and prognosisCo-morbiditiesPast, current and impending physical, drug and surgical treatmentsOther professionals involvedNon-medical factorsPhysical examination at baselineQuestionnaire tools as appropriate

Follow-up:SymptomsFocussed physical examinationOther professionals involved/missing from follow-upChanges in non-medical situationQuestionnaire tool as appropriateResponse to previous changes in treatment

The updated European Consensus 2009 on the use of Botulinum toxin for children with cerebral palsy. Eur J Paed Neurol 2009

Another case

• Case B: seen since 2008, now 17 years• 4 limb spastic-dystonic CP• Prematurity 30 weeks• GMFCS 5; MACS 5• Learning difficulties, dysarthric, oral feeder• Perseverative, anxiety issues• Bilateral hip reconstruction in 2002 and 2008• Oral baclofen 100mg/day – ongoing hip pain and

general discomfort

Dec 2008: Age 13

Mar 2010: Age 15

Mar 2010: Age 15

76 degree Cobb angleSpine flexible under traction

March 2012: Age 17 yearsITB dose 210mcg/day Posterior instrumentation ; anterior approach not requiredOut of hospital within 9 days

Post-operative problems

• Headaches, flashing lights• Has the ITB pump stopped working?• Has the catheter been cut or blocked?• Neuropathic pain and behaviour change

ITB and pain

• Case C; now 17 year old male• CP due to neonatal meningitis• Asymmetric 4 limb spasticity, left worse• GMFCS 5; MACS 5• Severe intellectual disability, blind, VP shunt• Previous bilateral hip surgery ’03• Increasing pain 2 years – focal and general

0

1

2

3

4

5

6

7

Pre-ITB ITB 85mcg/day ITB 90mcg/day

Score

ITB dose

CCHQ scores for Case C

Ease of cares

Positioning

Comfort

Interaction

Pre-ITB, T-1 (9 months prior to ITB implantation)

Pre-ITB pump implantation, T0

T1 (2 months post-implantation)

T2 (27 months post-implantation)

ITB infusion dose (mcg/day)

- 0 90.0 182.0

PPP Pain A (hip pain)

50 54 5 22

PPP Good day

14 - 5 11

MAS 1.08 1.78 0.6 0.16

Oral medications

Diclofenac 40mg tds, Tramadol 50mg tds

Diclofenac 40mg tds, Tramadol 50mg tds

Diclofenac 40mg tds, Tramadol 50mg tds

Diclofenac 40mg tds, intramuscular botulinum toxin injections

Patient number

Age at ITB pump implant

Co-morbidities Medication related to tone or pain management, at implantation

1 14

LD, EPILEPSY, SCOLIOSIS, VI, BEHAVIOUR Codeine, Paracetamol, Gabapentin Botulinum Toxin, Baclofen

2 16LD Baclofen

3 12

LD, EPILEPSY, PEG, RESP, SCOLIOSIS, HIPS Tramadol, Paracetamol, Tetrabenazine

4 13

LD, EPILEPSY, PEG, SCOLIOSIS, VI Dantrolene, Paracetamol, Nitrazepam

5 14

LD, EPILEPSY, SCOLIOSIS, HIPS, VI Diclofenac, Paracetamol, Tramadol, Botulinum Toxin, Baclofen

6 16

LD, SCOLIOSIS, VI Diclofenac, Baclofen, Trihexiphenidyl

7 14

LD, EPILEPSY, BEHAVIOUR Diclofenac, Baclofen, Trihexiphenidyl

8 13LD, EPILEPSY, PEG, VI, BEHAVIOUR Paracetamol, Baclofen

Findings

• Works for some types of pain (spasticity, neuropathic) more than others (osteoarthritic, visceral)

• In long-term, new sources of pain arise e.g. scoliosis, GI dysmotility

• Other intervention modalities also have a role, so not just about ITB “ITB is not a panacea”

Other specific issues

• Early and late complications: neurological, regional and systemic

• Often difficult to identify catheter blockage vs progression of underlying tone disorder vs tolerance vs response shift and mission creep

• Problems specific to standing transfer and indoor walkers (GMFCS 3 verging on 4)

• Athetoid-dystonic patients with and without spasticity

Summary• Patient selection and feasible goals important• Medical and non-medical factors important• ITB “success” vs “failure” only relevant to a 6

month time-frame• ITB long-term success only makes sense in

context of wider rehabilitative approach• Need help please – tall order for any single

service to do all of this• Additional advances in hardware, software and

pharmaceutics should improve matters

References• NICE Spasticity in children guidelines – due out soon• Dan et al. Consensus on the appropriate use of intrathecal baclofen (ITB)

therapy in paediatric spasticity. Eur J Paediatr Neurol 2010 14(1): 19-28.• Morton et al. Controlled study of the effects of continuous intrathecal

baclofen infusion in non-ambulant children with cerebral palsy. Dev Med Child Neurol. 2011; 53(8):736-41.

• Pin et al. Use of intrathecal baclofen therapy in ambulant children and adolescents with spasticity and dystonia of cerebral origin: a systematic review. Dev Med Child Neurol. 2011;53(10):885-95.

• Heinen et al. The updated European Consensus 2009 on the use of Botulinum toxin for children with cerebral palsy. Eur J Paediatr Neurol. 2010; 14(1):45-66.