HYPERTONIA MANAGEMENT IN CEREBRAL 10/12/2018 PALSY: PAST, PRESENT AND FUTURE

Hypertonia Management in Cerebral 1. Summarize the available tools for tone management, their potential limitations and Palsy: benefits. Past ideas and lessons, 2. Examine the current literature regarding the use of tone management modalities. Current practice and outcomes, Objectives: Future innovations and possibilities. 3. Explore less common uses of surgical techniques for symptom relief in . 4. Review current efforts with AACPDM 72 nd Annual Meeting, October 13, 2018 therapy in cerebral palsy and learn early patient results. Montreal, Quebec, Canada

 Sherrington, MD 1898  British Physiologist  Discovered a mechanism of The History of Hypertonia The History of  Spasticity developed from loss of inhibition Spasticity from the descending Management in Cerebral supraspinal structures Management  Developed neurosurgical Palsy techniques (in cats)  “dorsal th reduces spasticity in The 19 and 20th Century decerebrate animals”

 Foerster 1908  German Neurologist and Neurosurgeon  First dorsal spinal root surgery Surgery on  “Dorsal Rhizotomy” Peripheral  Lorenz 1887 Surgery on  LEs -- 1913  First peripheral neurectomy (Obturator Nerve)  159 patients with Nerves  In combination with orthopedic surgery (adductor myotomy and Spinal Roots  Take 5 roots completely, from L2 thru S2, sparing L4 tenotomy)  Use estim to be sure L4 extends the knee  Encouraging results The History of Spasticity  Stoffel 1912 The History of Spasticity Management  Tibial neurectomy (“spastic foot”) Management  LESSON: Tone reduction is great, but sensory deficits marked  Median neurectomy (“spastic pronation of the forearm and hand”)  UEs  C4 – T2, sparing C6  23 patients  Poor results: after 23 patients – abandoned the procedure --“satisfactory results in only a few”

 LESSON: dorsal rhizotomy is NOT reliably useful for UE spasticity

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Phenol in spasticity-history

Surgery on  Munro 1945 Spinal Roots  Ventral root sectioning for severe spasticity • Earliest use of phenol for spasticity- by intrathecal route  T12 –S1 – Nathan, 1959 and Kelly, Gautier-Smith, also 1959 simultaneously  Caused severe weakness reported intrathecal injections for relief of spasticity. The History of Spasticity Management  LESSON: “Reserve this for severe refractory tone as seen in anoxic • Nerve Blocks with aqueous phenol- Khalili and colleagues

BIs” in 1960’s • Phenol motor point blocks –Halpern and Meelhuysen in 1965

 Gros 1967  French neurosurgeon  Diazepam 1966  Introduced the concept of e-stim Oral  Binds near the GABA(A) receptor increasing GABA's affinity for Surgery on GABA(A) receptors, resulting in more presynaptic inhibition  Technique: Medications  Binds at the reticular formation (consciousness and alertness) and at Spinal Roots  Cut 80% (4/5) spinal polysynaptic pathways (stretch reflex)  L1-S1

The History of Spasticity The History of Spasticity  Produces generalized relaxation in spasticity and  LESSON: Leaving 20% allowed maintenance of sensory function in Management Management  Gracies et al. Muscle and Nerve, 1997 70% of patients

 LESSON: balance the side effects of sedation with tone reduction  Noted incidental improvement in UE tone and better speech and better swallowing function

Dorsal Root  Kottke and Heimburger 1970 Surgery on Entry Zone  Sindou 1972  Superior cervical rhizotomy for UE tone  Technique: Spinal Roots  C1-C3 surgery  “Microsurgical Rhizotomy” in the “dorsal root entry zone” and the  (not C4 2/2 preserving the diaphragm) dorsal horn, aka: the “DREZotomy” The History of Spasticity  (not C5-C6 2/2 preserving UE sensation) The History of Spasticity Management Management  LESSON: Recommended for use in severe quadriplegia (anoxia) and  hemiplegics with severe UE tone due to resultant severe flaccid LESSON: Only slightly reduces spasticity (?2/2 reducing tonic neck reflexes?)

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 Dantrolene 1973  Potentially effective against spasticity and athetosis  Long acting skeletal – effect is on the muscle rather than the CNS  Inhibits the release of Ca+ at the sarcoplasmic reticulum Oral  Found to be helpful in approximately 50% of the patients Oral  1977  GABA agonist binding at the GABA(B) receptors in the Medications  LESSON: significant side effect is weakness Medications where the primary sensory fibers end  Nance and Young, Phys Med Rehabil Clin North Am, 1996  Inhibits mono and polysynaptic reflexes  LESSON: hepatotoxicity (1.8%) is a rare but potentially fatal (0.3%)  Reduces muscle tone and improves movement The History of Spasticity complication The History of Spasticity  Milla and Jackson, J Inter Med Res, 1977 Management  Chan, , 1990 Management

 Levodopa 1972  Effect is at the

 LESSON: best used in those with  Rosenthal et al, Neurology, 1972

Surgery on Surgery on  Fraioli and Guidetti 1977 Spinal Roots  Technique: Spinal Roots  Fasano 1976  “Partial Dorsal Rhizotomy”  Technique:  Cut dorsal ½ of the root just before the dorsal-lateral sulcus  “Functional Dorsal Rhizotomy” The History of Spasticity The History of Spasticity  Use of bipolar e-stim to select abnormal nerve rootlets Management  LESSON: We can avoid sensory loss by leaving a large part of the nerve Management root intact.

Surgery on Surgery on  Garland and colleagues 1980 Peripheral  Gros 1977 Peripheral  Orthopedic surgeon  French Neurosurgeon  Musculocutaneus nerve for elbow flexion spasticity Nerves  Introduced the concept of unipolar e-stim to localize the functions of Nerves different fascicles of the nerve for more selective neurotomies  Brunelli and Brunelli 1983  Orthopedic surgeons The History of Spasticity  Sindou Lyon, France 1980 The History of Spasticity  Microsurgical partial neurotomies of the median nerve  Management Used bipolar e-stim and microdissection to further localize the nerve Management  Combined with finger and wrist flexor lengthenings functions and be further selective  Decq 1997  Sectioning of branches of the brachial plexus for shoulder spasticity

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 Peacock 1986 Selective Dorsal Rhizotomy: efficacy and safety in an Intraoperative monitoring during selective posterior rhizotomy: investigator-masked randomized clinical trial technique and patient outcome Surgery on Surgery on  McLaughlin et al, Dev Med Child Neurol, 1998, Vol 40, pp. 220-32  Technique described as needle electrodes placed in 5 muscle groups of  N=21 SDR + PT, N=17 PT only Spinal Roots each lower extremity: Spinal Roots  adductors  SDR was from L1 – S2 with 26% rootlets cut (range 14-50%)  quadriceps  SDR group had a significant reduction in spasticity, while the PT only The History of Spasticity  hamstrings The History of Spasticity group did not. Management  tibialis anterior Management  Ambulation status at 12 months was equivalent, but at 24 months  gastrocnemius the SDR group had exceeded the PT only group.

 after August 1991, an additional 2 electrodes were placed in the external anal sphincter   Electroencephalography and clinical Neurophysiology 97 (1995) 296-309 LESSON: SDR is excellent at reducing spasticity and improves gait outcomes overtime

Gait before and 10 years after rhizotomy in children with  Alpha 2 adrenergic agonists (Clonidine/Tizanidine) cerebral palsy spasticity ~1991 Surgery on  Subramanian et al, J Neurosurg, June 1998, Vol 88; pp. 1014-9. Oral  Hyperpolarize motor neurons Spinal Roots  N = 11 Medications  Decrease the release of excitatory amino acids  Immediate reduction in spasticity  Effect on interneurons  Improved ROM early and nearly normal ROM at 10 years post  Effect on presynaptic inhibition The History of Spasticity  No effect on cadence, but improved step length to normal range at 3 The History of Spasticity years post SDR Management Management  LESSONS: hypotension, depression, dry mouth, nausea/vomiting,  5/11 had orthopedic surgery reversible liver enzyme elevations (2-5%)  Young et al, Neurologist, 1997  LESSON: a control group needs to be studied to evaluate  Gracies et al, Muscle Nerve, 1997 definitively for benefits  Alonso, Semin Neurol, 1991

A Oral Injectable  First used by ophthalmologists for and blepharospasm  Gabapentin  1993 Medications  Structurally similar to GABA – does not activate GABA receptors, Medications  Koman, Mooney, Smith and Goodman --> tx'd instead it works by increasing brain levels of GABA equinus/equinovarus  Studied in MS, SCI and hemi-facial – not studied in CP  Wall et al. --> tx'd thumb in palm deformity The History of Spasticity The History of Spasticity  Management Management 1994  LESSON: consider it for use in cerebral palsy?  Cosgrove, Corry and Graham --> tx'd LE spasticity  1997  Corry, Cosgrove et al. --> tx’d hemiplegic UE spasticity

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 Synchromed Infusion System:  approved by the FDA in 1992 for spinal origin spasticity Botulinum neurotoxin for the treatment of spasticity  …in 1996 for cerebral origin spasticity (an evidence-based review): Report of the Intrathecal Injectable Therapeutics and Technology Assessment Baclofen (ITB) Intrathecal Baclofen In Cerebral Palsy Movement Disorders Subcommittee of the American Academy of  “ITB reduces spasticity in patients with cerebral palsy in doses lower Medications Pumps than oral baclofen with considerably greater effects. Neurology.  “Often ITB improves gait and upper extremity function.  Simpson DM et al.  “The Medtronic Pump is exceedingly reliable.   “Overdose errors are typically caused by programming errors and not The History of Spasticity Neurology® 2008;70:1691–1698 The History of Spasticity pump malfunction. Management  Critical review of the available literature Management  “ITB reduces generalized dystonia in cerebral palsy, though higher doses are typically needed c/w the treatment of spasticity.”  LESSON: Botulinum neurotoxin should be offered as a  Albright, J Child Neurol 1996; 11(Suppl 1): S29-35) treatment option for the treatment of spasticity in adults and Infusion of Intrathecal Baclofen for Generalized Dystonia in Cerebral children. Palsy  “In patients with dystonia, the average daily dose =575 mcg/day”  Albright, J , Jan 1998, Vol 88(pp.73-6)

Intrathecal Baclofen for Management of : Multicenter Trial AACPDM Treatment Outcomes Committee Review Panel:  Richard Gilmartin, MD; Derek Bruce, MD; Bruce B. Storrs, MD; Rick Abbott, MD; Linda Krach, MD; John Ward, MD; Karen Bloom, MD; William H. Brooks, MD; Dennis L. Johnson, MD; Joseph R. Madsen, MD; John F. Intrathecal McLaughlin, MD; Joseph Nadell, MD Evidence of the effects of intrathecal baclofen for spastic Intrathecal  J Child Neurol, Feb 2000, Vol 15 (2), pp.71-7. Baclofen (ITB) and dystonic cerebral palsy Baclofen (ITB) Pumps  Dev Med Child Neurol, 2000, Vol 42 (9), pp. 634-45  N=51, age 4-31 (mean = 10)  Available literature was researched and reviewed by the outcomes committee (1956-March 2000)

Pumps   44 patients proceeded to the long term trial  Spasticity:   followed 4-43 months (mean = 28 months)  N= 202 (likely overlap)  “the results for reduction of muscle tone, in general or in the lower extremities, was consistent and positive.”  Effective in reducing spasticity of cerebral origin.  Reduced impairment, improved function The History of Spasticity  Relatively safe The History of Spasticity  Complications: somnolence, hypotonia, headache, nausea, vomiting, Management  42/51 patients reported adverse events but hey were manageable Management  Nausea/vomiting  Dystonia:  Drowsiness  N= 15  Hypotonia  12 had clinically important improvement after short term infusion  Seizures  Somnolence  constipation  LESSONS: ITB is useful in treating spasticity and dystonia of cerebral  Minimally invasive origin, but further studies are needed; complications are common but  Reversible frequently manageable.

Reviewing Current Entering the 21st Century Practice Trends in Tone Management How we treat tone today

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Oral medications: Current Literature

(A short word on definitions as things may get a little confusing…)

• Hypertonia: significant increase in muscle tone as a result of lesion. Oral medications for Hypertonia: what does • Hypertonia and spasticity are often used synonymously, BUT spasticity is actually the current literature say? just one of the three clinical types of hypertonia, in addition to rigidity and dystonia.

– Spasticity is defined as velocity dependent hypertonia. – Dystonia is defined as a in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. – Rigidity is defined as hypertonia present at all rates of passive and active movement.

Oral medications: Current Literature Oral medications: Current Literature

• All recent papers discuss defining goals of care:

– Optimizing comfort / care

– Quality of life

– Freedom from medication side effects No new class A or B data are available for oral medications.

– Avoidance of polypharmacy impact as able in a patient with likely many comorbidities

Oral medications: Current Literature

Oral medications: But wait!: Current Literature

What to tell my patient then? • Levodopa/carbidopa • Acetazolimide • Trihexyphenidyl • Zonegran • Gabapentin • Carbamazepine • Clonidine • Tizanidine • Tetrabenazine • Dantrolene • Baclofen • Clonazepam

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Oral medications: Current Literature Oral medications: Current Literature

But wait!: • What does the data look like?

There is little evidence from randomised controlled trials on the best therapeutic strategies for the management of movement disorders in children; evidence to determine best practice for the management of abnormalities of tone and movement are particularly lacking.

Dystonia: Treatment Oral medications: • What dose the evidence look like? Current Literature

How to treat?

Oral medications: Current Literature

What next? Neurotoxins and alcohols Current practice trends & The Literature

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Scaglione 2016  Abobotulinum toxin A (Dysport)  Incobotulinum toxin A (Xeomin) Botox, Dysport,  Letibotulinum toxin A (Botulax) Xeomin  Onabotulinum toxin A (Botox) conversion Neurotoxins  Rimabotulinum toxin B (Myobloc)  Daxibotulinum toxin A (phase 1; 6-9 mon duration  Type A – E combo

 Abobotulinum toxin (Dysport)  Previously treated patients who improved  PLL spasticity equinus gait: randomized, double blind,  MAS placebo controlled trial  15U/kg/leg: 83%  High dose (15U/kg/leg, max 1,000 U) Abobotulinum  10U/kg/leg: 70% Delgado, et al  Placebo: 56%  Moderate dose (10U/kg/leg) toxin vs 2016  PGA  placebo Placebo  15U/kg/leg: 90%  Significant difference in MAS, PGA at 12 wks  10U/kg/leg: 87%  32% didn’t have return of spasticity >28 wks  Placebo: 63%

 144 pts w/ CP, equinus gait Botulinum toxin Chang, et al  Randomized to leti vs ona  Physician Rating Scale 2017:  Botulax: 60% improved letibotulinum  Botox: 61% improved vs  Modified Tardeau Scale: both improved onabotulinum  GMFM: both improved  Adverse events: no difference

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 Modify heavy chain of C terminus of A with B heavy chain  84 patients w/ CP  Increases distal axon binding by 350%  E-stim followed by U/S TrapoX  Delgado, et al More endocytosis of light chain  E-stim in muscle: botulinum  More blockage of acetylcholine by 4x unpublished  99% accuracy LE toxin  Increases duration of effect to 6-9 months  78% accuracy forearm muscles  Allows for less protein less frequently  Didn’t do it the other way around  Higher risk of distal weakness if spreads

  Grigoriu, et al E-stim vs U/S: no significant difference Picelli, et al Randomized controlled trial  EMG less accurate  Forearm muscles injected with btx 2015: 2013:  All better than manual palpation  MAS, Tardieu scale Comparing E- compared  EMG great for active muscles  U/S > palpation stim vs  All complimentary palpation, e-  E-stim > palpation Ultrasound  Can use palpation or motion to help with localization stim, U/S  U/S = E-stim

Dursun, et al 2017:  Randomized controlled trial Btx & PT vs Btx,  Randomized controlled trial  Btx for spastic equinus Hastings-Ison, PT, & casting  Spastic equinus in CP  Onabotulinum (Botox) into gastroc et al  Every 12 month group  Btx & PT vs Btx, PT, and 3 wks SLC 2015:  Every 4 month group  Both had significant improvements in PROM, MAS, Tardieu, OGS, PGA Btx frequency  6U/kg/leg  Casting group > non-casting group  No difference in ROM

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Carbolic Acid / phenyl alcohol Phenol C6H5OH Crystalline white solid, Commercial liquid Keep away from light

 Initially isolated from coal tar in 1834 Combination  Primarily man-made EMG & E-stim  Used in adhesives, construction, automotive and appliance industries  Nylon fibers  Disinfectant  Medical  Local anesthetic  Neurolytic  Chemical face peel

Phenol in spasticity:  Earliest use of phenol for spasticity- by intrathecal route  Nathan, 1959 and Kelly, Gautier-Smith, also 1959 history simultaneously reported intrathecal injections for relief of spasticity.  See attached Figure #1  Nerve Blocks with aqueous phenol- Khalili and colleagues in 1960’s  Phenol motor point blocks –Halpern and Meelhuysen in 1965

Wong, et al 2004 Phenol vs BTX Phenol or BTX used in Amb. CP in Ambulatory Gait analysis before and after treatment  See attached Figure #2 CP Increase in velocity and cadence, BTX > Phenol

(Glenn, 1990)

If get an H-reflex: inject!

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Ofluoglu, et al, Karri, Mas,  185 adults (n=293 2003 Francisco, Li  CVA 41%, TBI 29%, SCI 24% Retrospective 2017:  78% on oral spasticity Rx review of phenol Phenol decreases tone Retrospective  E-stim & U/S 69%, U/S 27% to obturator increases base of support review of phenol  3.5ml mean per nerve, 11ml mean total (less scissoring) while  Obturator 36%, sciatic 27%  55% had post-injection assessment  85% subjective improvement  Pain 4%, swelling 3%, dysesthesia 0.7%

Summary of Summary of Administration: Injected into motor Phenol Block Phenol Block  Can be used with botulinum toxin to allow more injection points of involved muscle (cont’d) sites and larger doses per site Duration of effectiveness: 4-12 months  A good phenol block can reduce tone better than botulinum toxin, but technically more difficult  Advantages  Most often use phenol for easy to find nerves, i.e.  Use is widely approved obturator and musculocutaneous; then use botulinum  Lasts longer than botulinum toxin toxin elsewhere  Cumulative effect often occur  Effective for plantarflexion and shoulder adduction

Summary of Summary of Complications Phenol Block Phenol Block  Transient dysesthesias and numbness (cont’d) Drawbacks (cont’d)  Hematomas possible, negating effects of  Can be painful treatment  May require general anesthesia during  With large intravascular injection, systemic administration effects such as muscle and  Takes more skill to administer convulsions, also depressed cardiac activity, blood pressure and respiration possible  Fibrosis or stiffness of muscle: “freezer burn”

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 Most common / easiest to inject Phenol Dosing Common  obturator nerves (to hip adductors)

Injection Sites  musculocutaneous nerve (to biceps)  30 mg/kg--Matthew, et.al.  7% = 70 mg/ml  Moderately difficult to inject  nerves to gastrocnemius, pectoralis, latissimus  5% = 50 mg/ml dorsi  0.5 ml/kg considered safe  Most difficult to inject  nerves to hamstring, forearm muscles

Hip Adductors  Anterior approach Hip Adductor - lat. to add. longus tendon  Medial approach - near inguinal posterior medial to crease add. longus tendon  superficial - ant. branch of  Post. branch 45º obturator angle posterior  deeper -  Ant. branch towards post. branch of ASIS obturator

Hip Adductors  Groove btw Phenol to gracilis and obturator add. magnus (try to get to < 1 mA)  Branch of obturator runs along ant. portion of muscle

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Gastrocnemius Biceps

 Distal to popliteal crease  Medial border  Lateral and medial to midline  1/3 from axillary  Avoid posterior tibialis  Avoid median nerve nerve and  Several motor points brachial artery

Patient Selection Patients refractory to more conservative treatment Multifocal spasticity not addressed by botulinum toxin alone Patients resistant to botulinum toxin Neurosurgery Current practice trends & The Literature

 Cauda Equina  Conus  Larger opening  Smaller opening  Anatomic Localization  Venous drainage adds risk  Most used  Less Bone Removal  Surgical technique  Long term spinal (laminectomy) Current  Rootlet selection instability if  Localization less precise laminectomy?  More urologic Practice trends  Short term outcomes data  Longer operative time? complications? SDR  More blood loss?  Less blood loss? in Selective  Long term outcomes data  Longer recover time?  Less painful? Dorsal  Additional research findings Technique

Rhizotomy  Keyhole Interlaminal Dorsal Rhizotomy  No bone removal  Microsurgery  Localization less precise  Predetermined percentage of rootlets based on clinical findings

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 Done differently at different institutions and by different surgeons  Many surgeons have many opinions on which  Most will explore levels L2 – S1 technique is best.  Some add L1 and/or S2 SDR  Some surgeons do one technique always SDR Rootlet  Some surgeons choose their technique based on goals of the Technique procedure, age of the patient, risks or patient/family preference Selection Non-selective: Gross—Selective: Micro—Selective:  No studies have been done comparing the outcomes of patients -- for instance, root is --for instance, root is --for instance, root is identified, divided into stratified by surgical technique identified and randomly identified, divided into three multiple rootlets (10-20+), a given percentage is cut parts, and each is stimulated and each is stimulated at the (25%? 50%? 75%?) at high level; the most lowest possible level and pathologic appearing are cut; evaluated for abnormality; 33-67% are cut. 20-40% are typically cut.

Summary of short term outcomes  No correlation has been identified between highly spastic muscle SDR Rootlet groups/levels and number of rootlets cut following monitoring  Many researchers have published on their short term outcomes with Selective Dorsal Rhizotomy Selection  Questions remain as to whether or not “selective” vs. “random” Current Practice trends root selection is superior. in Selective Dorsal Rhizotomy

 Many researchers have published on their short term outcomes with Summary of Selective Dorsal Rhizotomy short term Summary of outcomes Selective Dorsal Rhizotomy: meta-analysis of three short term randomized controlled trials outcomes  McLaughlin et al, Dev Med Child Neurol 2002, Vol 44: pp 17-25 Comprehensive short-term outcome assessment of selective dorsal rhizotomy.  Three short term outcome studies analyzed together Current Practice trends Current Practice trends  Trost JP, Schwartz MH, Krach LE, Dunn MB, Novacheck TF:  mostly patients <9 y/o, CP, and 25-45% rootlets cut in Selective Dorsal in Selective Dorsal  Dev Med Child Neurol, 2008, 50: 765–771  Rhizotomy f/u at 9 mons, or 12 months, or 12 and 24 months Rhizotomy  47 SDR patients total, 48 controls

 Conclusion: confirms clinically important change in spasticity; there is a small but statistically significant advantage in the SDR group -- improvement of GMFM by 4% (is this a meaningful difference?)

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Study Design Outcome Measures

Gillette Gait Index  Retrospective Analysis . Overall measure of gait pathology  Subjects Gillette Functional Assessment Questionnaire  Gait analysis 0-18 months prior to SDR . 10 level walking scale  Gait analysis 8-36 months subsequent to SDR Oxygen Cost  SDR performed at 1994 - 2003 . Net nondimensional cost  Gillette Children’s Specialty Healthcare, or Shriner’s Hospital for Children – Twin Cities Unit Ashworth Score . Sum of specific muscles

Subjects Outcome Categories

. Lost

Table 2 . Patient Characteristics . Pre: within typical range, Post: outside typical range Gender Number Age Follow -Up Time Poor . Worsened . Pre: outside typical range, Post: further outside typical range Mean SD . Unchanged

Female 55 7.6 2.1 1.1 81 6.9 2.0 1.0 . Pre : outside typical range, Post: outside typical range, no Male further/closer to typical (within exp. Error)

Total 136 7.2 2.1 1.1 . Maintained Neutral . Pre: within typical range, Post: within typical range Age and Follow -Up Time in Years . Improved

. Pre: outside typical range, Post: outside typical range, but closer to typical

Good . Corrected . Pre: outside typical range, Post: within typical range

Function: Gillette FAQ Function: Gillette FAQ

40

30 pre

20 Mean pre = 7.3

10 Mean pst = 8.2

G 40 0 1 2 3 4 5 6 7 8 9

i

l

l PreFAQ

e

t

t

e 30

F post Increase of 0.9 levels

A

Q 0 20 40 60 80 100 20 Percent of Subjects 10

corrected maintained worsened

0 1 2 3 4 5 6 7 8 9 improved unchanged lost pstfaq

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Function: Gillette FAQ

6 Walks more than 15-50 feet outside the home but usually uses or stroller for community distances or in congested areas Summary of 7 Walks outside for community distances, but only on level surfaces (cannot perform curbs, uneven terrain, or stairs without assistance of another person) long term outcomes  Many researchers have published on their long term outcomes with Selective Dorsal Rhizotomy Current Practice trends in Selective Dorsal 8 Walks outside the home for community distances, is able to get around on curbs and uneven terrain Rhizotomy in addition to level surfaces, but usually requires minimal assistance or supervision for safety

9 Walks outside the home for community distances, easily gets around on level ground, curbs, and uneven terrain, but has difficulty or requires minimal assistance or supervision with running, climbing and stairs

Summary of Summary of long term long term Level of activity and participation in adults with • 2011 spastic diplegic cerebral palsy 17-26 years post outcomes • F/U > 5 years, Pediatric patients, lumbar level SDR, cerebral palsy outcomes selective dorsal rhizotomy. • 21 articles  Langerak et al, J Rehabil Med, 2011, Vol 43; pp. 330-7 • 1998-2010 (966 children)  N=31 (age 21-44) • Only 3 studies showed level III evidence (45 children) •  SDR in 1981-1991 Current Practice trends Therefore, low strength and quality of evidence given low numbers. Current Practice trends • LESSONS:  GMFCS level I (48%), II (36%), III (16%). in Selective Dorsal in Selective Dorsal • positive long term effects on body structure and body function ICF  Functional Mobility Scale (performance/mobility in daily life) and Rhizotomy domains. Rhizotomy Life Habit Questionnaire (activity and participation domain) • Long term effects on activities and participation domains and risk of  Interview spinal deformities remain uncertain. *Interestingly, of the 3 level III studies examined, 2 found improvement in gait and one did not. The main difference between the studies: the two studies that found improvement in gait were on GMFCS level I-III patients and the study which showed no long term gait gains had an average GMFCS level of 3.8.

 Functional Mobility Scale Long-term functional benefits of selective dorsal  5 meters  29% independent on all surfaces Current Practice rhizotomy for spastic cerebral palsy Summary of  55% independent on level surfaces trends in  Dudley et al, J Neurosurg Ped 2013; vol 12; pp. 142-50 long term  16% use an assistive device  Conclusion: “benefits of SDR are durable through adolescence and  50 meters/500 meters Selective Dorsal into early adulthood” and include: outcomes  22% independent on all surfaces Rhizotomy  improved muscle tone  39% independent on level surfaces  gross motor function  12% use an assistive device  performance of ADLs Current Practice trends  Life-H Questionaire Summary of long  decreased need for adjunct orthopedic procedures or Botox in Selective Dorsal  Daily activities  Average of 81% of the participants were independent on each of the term outcomes injections Rhizotomy categories with no difficulty completing certain life habits  The area of largest concern was in “mobility”  Most likely to display these long-term benefits are those in GMFCS  36% were independent for all mobility tasks Groups I, II, and III, with:  48% were independent but with difficulties   16% had some mobility dependencies  less hip adductor spasticity  preoperative GMFM scores greater than 60

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Current Practice Current Practice trends in trends in Long-term effect of selective dorsal rhizotomy on gross A prospective cohort study investigating gross motor Selective Dorsal motor function in ambulant children with spastic Selective Dorsal function, pain, and health-related quality of life 17 years Rhizotomy bilateral cerebral palsy, compared with reference Rhizotomy after selective dorsal rhizotomy in cerebral palsy centiles.  Tedroff 2014  Bolster et al. 2012, Dev Med Child Neuro, Vol 55; pp. 610-6.  Dev Med Child Neuro, 57: pp. 484-90 Summary of long  N=29 (GMFCS level I-III) Summary of long term outcomes  Followed at 5 and 10 years post SDR term outcomes  Conclusion: Patient gross motor function was found to peak 3 years post SDR and declined by the 17 year f/u by GMFM score  Conclusion: none of the patients deteriorated in motor function 10 years post SDR.  N= 18

 Evaluate comprehensive outcomes 10-17 years after SDR  Spasticity  Gait  Function  Pain Comprehensive Long-Term Outcomes Following  Quality of Life • Activity  Subsequent Treatment Selective Dorsal Rhizotomy • Participation Goals ICF • DOMAINS Body Function and Structure Tom F. Novacheck, MD1 , Meghan E. Munger, MPH 1, Nanette Aldahondo, MD1, Linda Krach, MD2, Michael H. Schwartz, PhD1 1 Gillette Children’s Specialty Healthcare, St. Paul, MN, USA 2 Courage Kenny Rehabilitation Institute, Minneapolis, MN, USA  Test benefit of SDR compared to alternative treatments

Hypothesis SDR group SDR will lead to better outcomes and fewer  spastic diplegic CP subsequent treatments  SDR between 1995 and 2005 compared to a control group Inclusion  pre-SDR three-dimensional (3-D) Criteria computerized gait analysis  follow-up ≥ 8 years  16-25 years old at follow-up

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 Propensity Model (Random Forest Algorithm):  age SDR Baseline Follow-Up  gait Control  stature  function  CP subtype n=24 n=24 95% n=11 n=11 Strength:  treatment history  plantarflexor spasticity ACCURATE Gait Analysis & Surveys & n=13 Retrospectively Physical Exam Subsequent n=8 Timeline Full cohort Treatments Gait Analysis Identified Full cohort Physical Exam subset •Sensitivity: 80% SDR Control Group SDR group •Specificity: 98% time

•Pos. Pred. Value: 89%

•Neg. Pred. Value: 97% Treatment

date of of birth date

≥ 8 year follow-up

 No difference in pain  Surveys at follow-up  Both groups had “low pain interference”  Diener Satisfaction with Life Scale  No difference in QOL  World Health Organization’s Quality of Life-BREF Survey  Both group reported high QOL  Modified Brief Pain Inventory RESULTS Measures  Frequency of Participation Questionnaire  No difference in Gillette FAQ  Functional Assessment Questionnaire In brief…  Functional Mobility Scale  No difference in energy expenditure in gait  Spasticity better in SDR group  Fewer procedures in the SDR group (ortho and injections)  Improvement in GMFCS Level in the SDR group  Better GDI in the Control group

 In Hemiplegic CP  “Selective dorsal rhizotomy in children with spastic ”  Oki et al, J Neurosurg Ped, 2010, Vol 6: pp. 353-8  Reduced spasticity in all patients; improved gait in ~1/2 Current Practice Summary of trends in additional  Self Care and Mobility Selective Dorsal   “Functional performance in self-care and mobility after selective dorsal Gait: findings rhizotomy: a 10-year practice-based follow-up study” Rhizotomy  “Changes in gait which occur before and during the adolescent  Josenby et al, Dev Med Child Neurol 2015, 57; 286-293 growth spurt in children treated by selective dorsal rhizotomy “  McFall et al, Gait & Posture, 2015, Vol 42, pp. 317-22  All children from all GMFCS levels showed improved functional performance and Current Practice trends independence in daily activities up to 10 years postoperatively. Summary of in Selective Dorsal  17 patients followed over their adolescent growth spurt maintained additional findings significant post-SDR improvements thru that spurt into their early Rhizotomy adulthood.  Weight Gain  “Ambulatory children with cerebral palsy do not exhibit unhealthy weight gain following selective dorsal rhizotomy”  Gutknecht et al, Dev Med Child Neuro, 2015, 57: 1070-5

 No evidence of unhealthy changes in BMI post SDR.

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 “Analysis of complications in 430 consecutive pediatric patients treated with intrathecal baclofen therapy: 14-year Experience” Current  Motta et al Current  J Neurosurg: Pediatrics / Volume 13 / March 2014, pp. 301-6  Infection: Practice trends  Conclusion: Practice trends  9.5 % (Bayhan et al, J Pediatr Orthop 2016;36:305–309)  At least 1 complication was present in 25% of the patients in Intrathecal in Intrathecal  Surgical complication/return to OR  9.3% experienced an infection  25-40% (review: Kolaski et al, NeuroRehabilitation 2007, (22) 383–  4.9% a CSF leak Baclofen Baclofen 395)  15.1% a problem with the catheter Pumps  1% a problem related to the pump Pumps  Five percent of the assessed patients suffered more than 1 complication.

The effect of continuous intrathecal baclofen on sitting Controlled study of the effects of continuous intrathecal in children with severe cerebral palsy baclofen infusion in non-ambulant children with cerebral Gray et al 2014 Current palsy  Morton et al 2011  europ j ped neurol, vol. 1 8, pp.4 5-4 9 Practice trends ITB additional  Dev Med Child Neuro, 53: 736–741  Results: in Intrathecal  Followed the patients over 18 months research  No significant difference was found in sitting before ITB treatment  Caregiver Questionnaire was the main measure of quality of life: compared to sitting following insertion of an ITB pump. Baclofen  showed marked improvements in their overall score involving  No specific age group or classification of motor impairment demonstrated  comfort significant deterioration in sitting following ITB treatment. Pumps  positioning  Conclusion: Sitting does not improve or deteriorate in children following  transfers treatment with ITB, independent of age or severity of motor impairment.  personal care

 “IntraVENTricular baclofen as an alternative to intrathecal Current Long-term follow-up on continuous intrathecal Baclofen baclofen for intractable spasticity or dystonia: outcomes and therapy in non-ambulant children with intractable Current Practice technical considerations” Practice trends  Turner et al 2012, spastic Cerebral Palsy trends in  J Neurosurg: Pediatrics / Volume 10, pp. 315-9  Vles et al, 2013 in Intrathecal  N = 22  European J Neurol, Vol 1 7, pp. 6 3 9 -4 4 IntraVENTRICULAR  1998-2010 Baclofen  Results: decreased pain, improved ease of care, improved mental  Offered to patients who failed ITB therapy health Baclofen Pumps Pumps  This article describes the lower complication rate with IVB  It does not describe any tone outcomes  *essentially abandoned at this time*

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DBS: Quick Review

• In the US in 2003, the Medtronic Activa DBS device was granted limited FDA approval for primary and segmental dystonia in patients 7 years and older under a Humanitarian Device Exemption.

Deep Brain Stimulation Current trends & The Literature • The exemption allows targeting of the pars interna (GPi) nucleus OR the subthalamic nucleus (STN).

http://www.mayfieldclinic.com/Images/PE-DBS_fig2.jpg

DBS: Quick Review DBS: Quick Review

DBS: Current DBS: Current Literature Literature • Reviewing a few select studies oldest to newest

• Vidailhet 2005, prospective multicenter trial in patients with

• Dystonia primary or secondary or something primary generalized dystonia who received double blind video new? assessment 3 months after surgery:

• Jinnah 2014, A new classification! – 29% improvement in the BFMDRS-m scale with DBS on compared to off. – After 12 months these patients with DBS turned on showed a 51% reduction in BFMDRS-m and 44% improvement in disability score.

Mov Disord Clin Pract, 1: 280–284.

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DBS: Current Literature DBS: Current Literature • Cif 2010, long-term follow-up of DYT1 dystonia patients treated by DBS on an open- • Kupsch 2006, DBS for primary generalized or segmental label study: dystonia with double blind, multi-center, randomized trial controlled with sham stimulation for 3 months.

– DBS improved scores BFMDRS-m and disability scores by 39.8% and 38% compared to baseline. – Sham group showed only 4.9% and 11% improvement in commensurate scores.

DBS: Current Literature DBS: Current Literature • Mills 2014, secondary (structural) dystonia and DBS review of available literature: • Debate: Schjerling 2013, randomized double-blind crossover trial comparing subthalamic and pallidal deep brain stimulation for idiopathic (sporadic) / tardive dystonia

DBS: Current Literature

• Much controversy still surrounds:

– Patient selection – Implantation method – Multiple target stimulation (STN + GPi?) Palliative Rhizotomy – The future of shaping stimulation fields Current trends & – Electrophysiological biomarkers that might provide real time The Literature feedback to assist with chrono-stimulation OR Future Directions and possibilities

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 Ventral and dorsal rhizotomy  For GMFCS IV-V  Conus or cauda equina level  Usually severe dystonia +/- spasticity  Non-selective Palliative Palliative  Usually permanent tone reduction  Aggressive percentage of rootlets cut Rhizotomy Rhizotomy  Can see some return of dystonia after 1-2 years  50-75% at each level  Can do cervical roots too  L1-S2 typical  Gillette has 30 patients and a very large majority has a  Can decrease standing; weakens significant improvement

 50 pts. with CP Ghany, et al,  Mixed dystonia and spasticity Albright, Tyler-  L1-S1 laminotomy and roots  6 pts with spastic and dystonic CP, GMFCS IV-V 2016: Kabara,  50-80% of dorsal rootlets selectively cut  Not candidates for ITB Ventral and 2007:  4-6 ventral rootlets dissected per root  Long-term improvement in dystonia and spasticity Dorsal Palliative  50-80% of ventral rootlets dissected  No adverse effects Rhizotomy for Rhizotomy  At 12 mon MAS mean dropped from 4 to 2 CP  BAD scale significantly dropped 25 to 12

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