A Neurosurgical Perspective

Document Sample
A Neurosurgical Perspective Powered By Docstoc
					                          CM E

         Management of
         Childhood Spasticity:
A Neurosurgical Perspective
         Christopher E. Mandigo, MD; and Richard C.E. Anderson, MD

                 pasticity is a vexing problem for       or damage to the developing CNS. Spas-
                 both healthcare providers and pa-       ticity is demonstrated in children as in-
                 tients. Cerebral palsy is the most      creased muscle tone, persistent primitive
         common cause of spasticity and physical         reflexes, and delay of normal motor skills.
         disability in children. It defines a range of    Spasticity inhibits effective use of motor
         nonprogressive syndromes of posture and         control and strength and can lead to pro-
         motor impairment that results from an           gressive musculoskeletal complications
         insult to the developing central nervous        such as joint and muscular contractures,
         system (CNS) either in utero or within          bony deformation, and joint subluxation
         the first 2 years of life.1 The prevalence       or dislocation.5 Proper treatment for spas-
         of cerebral palsy is not known but is esti-     ticity can halt progression of contractures
         mated at approximately 2 per 1,000 chil-        or deformity and often can return func-
         dren, and its incidence may be increasing       tion to affected limbs. Both prospective
         secondary to improved care in neonatal          and retrospective studies of children
         intensive care units and improved surviv-       treated for spasticity have demonstrated
         al of low birth-weight infants.2 The com-       improved ease of caregiving, decreased
         mon features of cerebral palsy include          pain, and improved quality of life.6
         movement disorders, muscle weakness,                Spasticity in children can result from
         ataxia, rigidity, and spasticity.               any disease process that affects the upper
            Spasticity is defined as a velocity-          motor neuron within the CNS. Injury to
         dependent increased resistance to pas-          the upper motor neuron decreases corti-
         sive muscle stretch, or alternatively as        cal input to the descending reticulospinal
         inappropriate involuntary muscle activity       and corticospinal tracts, which causes
         associated with upper motor neuron pa-          weakness, loss of motor control, and re-
         ralysis.3,4 It is a hallmark of cerebral pal-   duction in the number of voluntarily ac-
         sy but can occur with other genetic and         tive motor units. The reduction of these
         metabolic diseases that cause dysfunction       descending tracts removes the normal

354                                                               PEDIATRIC ANNALS 35:5 | MAY 2006
inhibition of the reflex arcs within the      evidence of hemorrhage, hydrocephalus,       other healthcare professionals, is best
grey matter of the spinal cord, leading to   or structural abnormalities of the CNS.      suited to treat children with spasticity.
a hyperactive reflex arc and spasticity.      Spasticity is most commonly quantified        Therapy should be guided by the clini-
   The diagnosis of spasticity requires      by the Ashworth spasticity scale (Table      cal scenario and specifically targeted at
a complete history and physical exami-       1, see page 356).7,8                         treating pain, decreasing tone, and re-
nation, with ancillary testing as needed.                                                 ducing muscle contractures, joint defor-
The history should inquire about pos-        MANAGEMENT                                   mities, and abnormal motor control.
sible gestational and perinatal events           Treatment of spasticity involves mul-       Spasticity should be addressed at an
and motor and cognitive development.         tiple modalities that most commonly          early age to prevent permanent contrac-
The physical examination should focus        include observation, physical and oc-        tures, joint subluxation, dislocation, and
on motor power, muscle tone, active          cupational therapy, orthotics, oral medi-    bony deformity. In general, young children
and passive range of motion of joints,       cines, intramuscular injections, and both    generally respond well to physiotherapy,
sensation, deep tendon reflexes, station      neurosurgical and orthopedic surgery.        orthotics, intramuscular injections, and
(pelvis and leg alignment while stand-       A combination of methods is employed         neurosurgical procedures. Older children
ing), presence of limb deformity, spinal     most often to increase the beneficial ef-     benefit from these therapies as well but
alignment, and extent of movement dis-       fects of each modality synergistically. A    also may need orthopedic surgery to ad-
orders. Ancillary testing usually includes   multidisciplinary team, including pedia-     dress musculoskeletal deformity.
imaging studies such as cranial ultra-       tricians, physical and occupational ther-       An approach directed by the location
sound, computed tomography, or mag-          apists, neurologists, orthotists, orthope-   and severity of the spasticity is used to
netic resonance imaging to evaluate for      dic surgeons, neurological surgeons, and     identify the appropriate therapeutic in-

PEDIATRIC ANNALS 35:5 | MAY 2006                                                                                               355
tervention. These therapies should be                                                         TABLE 1.
directed toward achieving goals deter-
mined in concert with caregivers, and                                  Ashworth Scale of Muscle Tone4,7
ideally should be monitored by the use               Ashworth Scale   Degree of Muscle Tone
of clearly defined outcome measures.6
                                                           1          No increase in tone
                                                           2          Slight increase in tone, “catch” when limb is moved
Nonpharmacologic Therapy
                                                           3          Marked increase in tone, passive movements difficult
   Physical and occupational therapy,
                                                           4          Considerable increase in tone, passive movements difficult
orthotics, and casting are just a few
                                                           5          Affected part is rigid in flexion or extension
of the nonpharmacologic and surgical
therapies employed to improve joint
range of motion, strengthen muscles, in-
hibit spastic agonist muscles, and assist        Oral Medications                                   cal situation and age of the patient as the
with motor development. There is a lack             Oral medicines are used often to re-            natural course of specific musculosk-
of evidence-based information address-           duce spasticity. The most common agents            eletal abnormalities is factored into the
ing these therapies for the treatment of         are baclofen, diazepam, dantrolene, and            decision-making process.
spasticity, largely because commonly             tizanidine. These have different mecha-
used outcome measures have not been              nisms of action with the common goal               Neurosurgical Therapy
validated or may not be functionally             of reducing spasticity. Several medi-                 The role of the neurosurgeon in the
relevant.9 However, decades of clinical          cines are summarized in Table 2 (see               treatment of spasticity is essential. A
experience support their use for maxi-           page 357). Additional novel agents that            variety of surgical procedures and treat-
mizing the benefit of medical and surgi-          are under investigation include canna-             ment options have a proven long-term
cal intervention.                                binoids, gabapentin, and 4-aminopyri-              and significant effect on spasticity in
                                                 dine. Although improvements in clinical            appropriately selected patients. These
CM E      EDUCATIONAL OBJECTIVES                 measures of spasticity have been noted             procedures include chemical or surgical
                                                 with several of these medications, few             neurotomies, botulinum toxin injections,
  1. Recognize the importance of early
     identification and intervention in           have shown significant functional ben-              selective dorsal rhizotomy, and chronic
     an infant or child with spasticity.         efit. Unfortunately, limiting side effects          intrathecal baclofen therapy.
  2. Discuss the pathophysiology of              often are reached before a clinically sig-            Selective neurotomy. Selective neu-
     upper motor neuron lesions and              nificant effect of the medication can be            rotomy, or surgical and chemical lesion-
     their effects on muscle.                    obtained. Antispasmodic medications                ing of peripheral nerves, has been prov-
  3. Describe the management of a                are very useful adjuncts to more invasive          en to be effective in treating spasticity.
     child with spasticity and the cre-          therapies and physiotherapy.10                     This can be accomplished in three ways:
     ation of a care plan, including phar-
     macologic and surgical options.                                                                through surgical exposure and transec-
                                                 Orthopedic Surgery                                 tion of all or a portion of the nerve;
     Dr. Mandigo is resident and Dr. Ander-         A wide variety of surgical options are          through injection of ethanol or phenol
  son is assistant professor, pediatric neu-     available for the orthopedic surgeon to            around the nerve; or through blockade
  rosurgery, Department of Neurological          treat spasticity and its long-term conse-          of the neuromuscular junction by botu-
  Surgery, The Children’s Hospital of New        quences on the musculoskeletal system.1            linum toxin injection. Recently, ethanol
  York, Columbia University, New York, NY.       In general, orthopedic procedures have             and phenol injections have largely been
     Address reprint requests to: Richard C.E.   been used to improve the biomechanics              set aside, as the favored technique has
  Anderson, MD, Division of Pediatric Neu-       of spastic patients. Some common goals             become botulinum injection of spastic
  rosurgery, Columbia University Medical         of surgery include lengthening of con-             muscles.
  Center, 710 W. 168th St., 2nd Floor, Neu-      tracted muscles, balancing of joint forces,           The objective of surgical neuroto-
  rological Institute, New York, NY 10032; or    reduction of joint subluxation, fusion of          my is to expose and isolate the nerve
  e-mail rceanderson@yahoo.com.                  unstable joints, and dimishment of pain-           branches that supply the spastic muscle.
     The authors disclosed no relevant fi-        ful spasticity. The surgical techniques in-        A complete or partial division is then
  nancial relationships.                         clude tenotomy, arthrodesis, osteotomy,            performed depending on both the par-
                                                 and tendon transfer or lengthening. The            ticular muscle involved and a pre-opera-
                                                 procedures used are tailored to the clini-         tive plan designed to balance spasticity

356                                                                                                             PEDIATRIC ANNALS 35:5 | MAY 2006
with motor weakness. The technique in-           not currently approved by the Food and            denervating a spastic muscle. Although
volves intra-operative neurophysiologic          Drug Administration for spasticity, BTX           specific timing varies, the effects of BTX
monitoring and active stimulation of the         has been used clinically since 1988 to            generally begin after 1 to 3 days, peak
nerves to better target destructive lesion-      treat spasticity associated with cerebral         around 21 days, and usually have little ef-
ing. Stimulation also may provide some           palsy. At least two subtypes are available        fect after 3 to 4 months. The dose of BTX
guidance to muscle strength and how it           in the United States, BTX-A (Botox) and           injected varies according to the muscle
relates to the amount of nerve lesioning         BTX-B (Dysport).                                  size and formulation of the toxin, but in
that is acceptable before motor function                                                           general a dose of 2 to 6 U per kilogram of
is lost completely.                                                                                body weight is used.12 BTX can be inject-
    Percutaneous neurotomy is performed              The physical examination                      ed into spastic muscles with or without
by injecting either alcohol or phenol to                                                           the use of electromyography guidance.
sclerose the nerve, which causes partial          should focus on motor power,                         A number of randomized clinical tri-
or complete destruction of the nerve                  muscle tone, active and                      als have demonstrated the efficacy and
supply to muscles. Localizing the nerve                                                            safety of BTX injections.13-16 These trials
is performed with anatomic landmarks                passive range of motion of                     have demonstrated a significant reduc-
and neurophysiologic testing through              joints, sensation, deep tendon                   tion in spasticity and improved function
the needle. The relative indications for                                                           in both lower and upper extremities. The
selective denervation are spasticity, joint      reflexes, station (pelvis and leg                  drug has a very good safety profile and
imbalance secondary to spasticity, and                                                             has infrequent side effects, mostly related
decreased function. Ethanol is used more
                                                    alignment while standing),                     to an allergic reaction to the medicine.17
in children because it is less caustic than         presence of limb deformity,                        Selective dorsal rhizotomy. Selective
phenol to surrounding tissues.                                                                     dorsal rhizotomy (SDR) derives from
    Ethanol and phenol denervation lasts
                                                 spinal alignment, and extent of                   late 19th Century procedures for spastic-
about 3 to 8 months. Potential compli-                 movement disorders.                         ity, during which a complete rhizotomy
cations and side effects include pain,                                                             was performed — the entire nerve root
permanent muscle fibrosis, and dyses-                                                               within the spinal canal was transected.
thesias. The obturator nerve is the most             When BTX is injected into spastic             These initial attempts effectively elimi-
commonly targeted nerve. Lesions in the          muscle tissue, it acts at the neuromus-           nated pathologic tone and spasticity but
nerve can help stop or prevent progres-          cular junction to inhibit the release of          resulted in clinical failure because of
sive subluxation secondary to hip adduc-         acetylcholine and balance muscle forces           complete loss of motor function, pain
tor spasticity.                                  across the joint.11 BTX acts locally, so it       sensation, and proprioception function.
    Botulinum toxin injections. Botuli-          is not effective in reducing global spas-         The procedure was abandoned until the
num toxin (BTX) injections have been             ticity. The general indications for BTX           1960s, but a modification of this ap-
used increasingly in place of alcohol and        are for temporary management of focal             proach has now been accepted as an ef-
phenol for chemodenervation. Athough             spasticity and to evaluate the effects of         fective treatment for spasticity.

                                                                     TABLE 2.

                               Oral Medications Used in the Treatment of Spasticity
   Medication              Mechanism of Action          Half-Life       Initial Dosage         Maintenance                Side Effects
                                                                                               20 to 90 mg/day            Drowsiness, ataxia,
   Baclofen (Lioresal)     GABAB agonist                3 to 4 hrs      2.5 to 10 mg/day
                                                                                               (in three doses per day)   confusion

                           Benzodiazepine receptor                                             0.1 to 0.8 mg/kg/day
   Diazepam (Valium)                                    3 to 6 hrs      0.1 to 0.2 mg/kg/day                              Lethargy, tolerance
                           agonist                                                             (in three doses per day)

                           Impedes Ca2+ influx into                                             12 mg/kg/day               Weakness, diarrhea,
   Dantrolene (Dantrium)                                3 to 9 hrs      0.5 to 1.0 mg/kg/day
                           muscle                                                              (in four doses per day)    rash, liver

                           Alpha-2 adrenergic agent;                                           8 to 24 mg/day             Sedation, dizziness,
   Tizanidine (Zanaflex)                                 2 to 3 hrs      4 to 8 mg/day
                           inhibits aspartate output                                           (in four doses per day)    hypotension

PEDIATRIC ANNALS 35:5 | MAY 2006                                                                                                                 357
Figure 1. Schematic drawings representing the excitatory and inhibitory influences on the spinal cord alpha motor neuron, which innervates the muscle
fibers. (A) Normal physiology with a balance of inhibitory influence from descending neurons and excitatory influence from the sensory spinal reflex arc. (B)
In children with spasticity, injury to the upper motor neuron results in a decrease in the descending inhibitory influence, leaving a hyperactive spinal cord
reflex arc. By cutting some of the dorsal rootlets, selective dorsal rhizotomy can help restore balance to the alpha motor neuron by reducing the amount of
excitatory influence on the alpha motor neuron.

    SDR was made possible after the ex-              on the activity of the alpha motor neu-                   Traditionally, surgery for SDR has in-
act anatomical localization of the Ia sen-           ron. These interneurons generally have                volved a 5- to 6-inch skin incision and a
sory input to the spinal cord at the dorsal          an inhibitory effect on the alpha motor               five-level laminectomy or laminoplasty.
root entry zone (DREZ) by Sindou in                  neuron and are activated by descending                More recently, SDR can be performed
1974.18 It is believed that these sensory            input from cortical upper motor neurons               using a minimally invasive approach.
fibers help mediate the abnormal reflex                (overall inhibitory influence to the mus-              Surgery now can be done through a
arc in spasticity. In principle, selective           cle). On the other hand, interneurons are             small (approximately 1- to 2-inch) in-
lesioning of these fibers could result in             inhibited by the local spinal reflex arc,              cision over the lower back and a single
loss of tone without loss of other sensory           which are mediated by Ia sensory fibers                level lumbar laminectomy.20 Intraop-
input or motor control at that spinal cord           (overall excitatory influence to the mus-              erative ultrasound is used to confirm the
level. This finding was further supported             cle). With damage to the brain or spinal              location just caudal to the conus, and
by the discovery of neurophysiological               cord, the balance of input is disrupted               the dura is opened to expose the conus
techniques that help differentiate nerve             and the reflex arc becomes hyperactive,                and nerve roots. Individual dorsal nerve
rootlets responsible for spasticity from             leading to increased limb tone and spas-              rootlets are then tested using electri-
normal rootlets uninvolved in the dis-               ticity. By selectively lesioning sensory              cal stimulation and neurophysiological
ease process. This method, originally                nerve rootlets, SDR reduces the amount                monitoring. Sensory rootlets that result
described by Fasano, uses electric stim-             of Ia sensory input and helps restore a               in spastic responses when stimulated are
ulation of dorsal sensory rootlets with              more normal balance to the alpha motor                identified as “abnormal” and transected
30 to 50 hertz sustained impulses to ac-             neuron (Figure 1).                                    according to a pre-operative plan based
tivate the hyperactive reflex arc.19 These                SDR is used primarily to treat chil-              on the patient’s pattern of spasticity
stimulated motor responses are thought               dren with lower extremity spasticity,                 (Figure 2, see page 359). The physical
to occur in the abnormal nerve rootlets              or spastic diplegia. Decades of clinical              therapy team is very helpful in the oper-
because of the loss of descending corti-             experience suggest that the patients who              ating room to manually palpate muscle
cal inhibitory pathways.                             ultimately benefit the most from SDR are               groups and provide physiological feed-
    The ability of SDR to reduce spas-               those with pure spasticity involving the              back during stimulation.
ticity can be explained by the current               lower extremities, normal intelligence,                   Recovery from surgery typically
pathophysiological understanding of                  good strength, no fixed contractures, and              takes 2 to 3 days, followed by discharge
spasticity. Motor control and tone of the            postural stability. The ideal patient age             to home with intensive outpatient re-
muscle ultimately are controlled by the              is still not known and is probably best               habilitation or to acute inpatient reha-
alpha motor neuron in the spinal cord.               determined by the individual clinical                 bilitation. Long-term physical and oc-
Interneurons within the spinal cord                  scenario. The typical age ranges from 3               cupational therapy is employed to insure
grey matter have a regulatory influence               to 8, but adolescents benefit as well.                 optimal outcomes.

358                                                                                                                  PEDIATRIC ANNALS 35:5 | MAY 2006
                                          One Dorsal Root                            Normal EMG: Fascicle             function in children with spastic diple-
         Conus Under                                                                 Placed Behind Silastic           gia. Interestingly, multivariate analysis
         Cotton Patty
                                                                                                                      in the selective dorsal rhizotomy group
                               Scheer Needle                                                                          also revealed a direct relationship be-
                                                                                                                      tween percentage of dorsal root tissue
                                                                                                                      transected and functional improvement.
                                                                                                                      A review of the literature supports the
                                                 B               C                    D                               findings summarized in Table 3.
                                                             Tetanic Stimulation                                          Complications occasionally can be
                            Peacock Rhizotomy Probes             of Fascicle
                                                                                                                      seen following SDR, the most common
                           Short Burst                               Nerve Roots
                                                                                                                      being pain or transient neurologic dys-
                           Stimulus to Whole                         to be Tested
                                                                                                       Sectioned      function including weakness, sensory
                           Dorsal Root                                                                 Fascicles
                                                                                                                      loss, or bladder dysfunction. The major-
                                                                                                        Fascicles     ity of these are temporary, with perma-
     A                                                               F                                                nent dysfunction occurring in less than
                                                                                                                      5% of patients. Retrospective studies
                           Abnormal EMG:
                         Fascicle Sectioned,
                                                                                                                      have drawn attention to the possibility
                        Placed Behind Silastic                                                                        of an increased incidence of scoliosis
                                                                                                                      and hip subluxation after SDR. Because
Figure 2. Illustration of steps shows sparing and sectioning the dorsal root fascicles during selective               these conditions are common in chil-
dorsal rhizotomy. (A) An innervation pattern of each dorsal root is examined by electromyographic
(EMG) responses to electrical stimulation with a threshold voltage. (B) A dorsal root is subdivided into
                                                                                                                      dren with spasticity who do not undergo
four to seven smaller rootlets of equal size. (C) The rootlets are tested for EMG responses. (D) Rootlets             SDR, it is unclear what role SDR plays
spared from sectioning are placed behind and covered by the Silastic sheet. (E) Rootlets producing 3+                 in the development of scoliosis or hip
or 4+ responses are sectioned. Bipolar cautery is seldom used for hemostasis. (F) Dorsal roots remain-
ing over the Silastic sheet are those requiring EMG examination. Spared rootlets are placed behind the                subluxation.23-25 It remains to be seen
Silastic, and sectioned rootlets are left on the side of the Silastic. No dorsal rootlet is left over the Silastic    if minimally invasive SDR through a
after the EMG testing and the sectioning of the dorsal rootlets are completed.29
                                                                                                                      single level laminectomy rather than a
                                                                                                                      multilevel laminectomy reduces the in-
   There have been a number of ex-                         or physiotherapy alone. Outcome mea-                       cidence of these conditions.
cellent long-term outcome studies for                      sures were used for spasticity (Ashworth                       Baclofen. Baclofen was first used pa-
SDR. The outcome measures examined                         scale) and function (Gross Motor Func-                     rentally for spasticity in the late 1960s.
include muscle tone, flexibility, gait                      tion Measure) and applied at a 12-month                    Baclofen works as an agonist of gamma
pattern, functional positioning, and the                   follow-up visit. As shown in Figure 3                      aminobutyric acid (GABA) at GABA-B
ability of the child to deal with his or her               (see page 360), selective dorsal rhizot-                   receptors within the dorsal horn of the
environment. Nearly all studies investi-                   omy with physical therapy was more ef-                     spinal cord. Activation of these receptors
gating SDR have demonstrated a signifi-                     fective than physical therapy alone in re-                 is thought to inhibit the excitatory input
cant and persistent decrease in spasticity                 ducing spasticity and improving overall                    to the alpha motor neuron. The effective-
without a return of hypertonicity over
                                                                                                                TABLE 3.
time. Improved function and ambula-
tion are commonly seen regardless of                                                  Summary of Reported Outcomes
the pre-operative abilities. Despite the                                            Following Selective Dorsal Rhizotomy
impressive decrease in spasticity after
                                                                Class I              Decrease in lower limb spasticity (Ashworth scale); up to 12 years
the procedure, some patients still suffer                                            Increase in lower extremity range of motion; up to 5 years
from loss of joint mobility and require                                              Improvement in motor function (Gross Motor Function Measure)
subsequent orthopedic surgery for ten-                          Class II             Improvement in disability (Pediatric Evaluation of Disability Inventory) and
don lengthening or transfer.                                                         activities of daily living performance
   McLaughlin et al. reported a compar-                                              Improvement in gait including increased stride length and velocity
ative analysis and meta-analysis of three                                            Improvement in suprasegmental effects including upper limb function
                                                                                     and cognition
randomized clinical trials in 2002.21,22
Eighty-two children with spastic diplegia                       Class III            Reduce the need for future orthopedic procedures

received either SDR and physiotherapy

PEDIATRIC ANNALS 35:5 | MAY 2006                                                                                                                                    359
                                                                        long term therapy with         and the daily administration of care.29
  A                                                                     baclofen. All patients
                                                                        experienced decreased
                                                                                                       The second group includes those chil-
                                                                                                       dren with a spastic diparesis that use
                                                                        muscle tone, and there         their increased tone for ambulation and
                                                                        were minimal compli-           functional mobility. If an SDR is per-
  Ashworth Change

                                                                        cations. The safety and        formed in these children, the concern
                                                                        efficacy of chronic in-         is that the significant reduction in tone
                                                                        trathecal therapy in adult     might impair function. ITB therapy can
                                                                        patients was reported          be effective because the intrathecal dos-
                                                                        in 1993.27 A total of 93       ing can be titrated to balance tone reduc-
              Vancouver   Toronto           Seattle        All
               P < .001   P = .003         P < .001     P < .001*       patients with intractable      tion with functional improvement.
                                                                        spasticity due to either           All potential candidates for ITB
     B                                                                  spinal cord injury, mul-
                                                                        tiple sclerosis, or other
                                                                                                       therapy are first evaluated with a trial
                                                                                                       injection of intrathecal baclofen. After
                                                                        spinal pathology were          the patient receives a thorough base-
                                                                        entered into a random-         line evaluation by the spasticity team,
      GMFM Change

                                                                        ized, double-blind, pla-       a bolus of 50 micrograms of baclofen
                                                                        cebo-controlled screen-        is given into the spinal fluid through a
                                                                        ing protocol of (ITB)          lumbar puncture. Anti-spastic effects of
                                                                        test injections, and 75        intrathecal baclofen can be seen within
                                                                        underwent implantation         30 minutes, peak between 2 and 4 hours,
                                                                        of a programmable pump         and wear off after 6 to 8 hours. Serial ex-
               Vancouver      Toronto          Seattle        All       system for chronic ther-       aminatons are then performed approxi-
                P = .012      P = .008        P = .649     P = .008*    apy. Patients were fol-        mately every two hours to determine its
                                                                        lowed for 5 to 41 months       efficacy. A reduction by one point on the
Figure 3. Summary of meta-analysis data after selective dorsal rhizot-
omy. Ashworth change score (A) and Gross Motor Function Measure
                                                                        after surgery (mean =
(GMFM) change score (B) are shown for those receiving physical ther- 19 months). The results
apy only and selective dorsal rhizotomy plus physical therapy group of this study indicated
data for individual studies and pooled meta-analysis. Interval is from                                     The objective of surgical
baseline to 12 months after beginning treatment (9 months for Van- that intrathecal baclofen
couver). Boxes represent the 25th, 50th, and 75th percentiles. Whiskers infusion was safe and ef-        neurotomy is to expose and
represent minimum and maximum values excluding outliers beyond
1.5 times the interquartile range. P values are based on Wilcoxon’s fective for the long-term          isolate the nerve branches that
tests, with blocking on site for combined tests.21                      treatment of intractable
                                                                        spasticity. The first trial       supply the spastic muscle. A
ness of oral baclofen may be limited by                reported in children was by Albright et          complete or partial division is
dose-related side effects such as seda- al.28 in 1991, which also demonstrated
tion, respiratory depression, confusion, significantly reduced spasticity with an                               then performed.
and hallucinations. Baclofen penetration acceptable complication rate.
into the central nervous system is also                    In the clinical setting, it often is dif-
limited by the blood–brain barrier.                    ficult to determine which patients are           Ashworth scale is considered a positive
    Impressive results from intrathecal better suited for SDR and which are bet-                       response and is seen in approximately
administration of baclofen (ITB) were ter for ITB therapy. Two main groups                             90% of patients. Escalating doses of 75
first demonstrated in adult patients with               of children generally have a better out-        or 100 micrograms of intrathecal ba-
spasticity from spinal cord injury or come if treated with ITB therapy. The                            clofen can be attempted if the first dose
multiple sclerosis. A dramatic reduc- first group includes those who have a                             is unsuccessful.
tion of tone was achieved with dosages severe spastic quadriparesis, are func-                             Implantation of a pump to administer
that were many orders of magnitude less tionally debilitated, and are completely                       baclofen continuously can be undertak-
than oral or parental doses. Penn et al.26             dependent for care. These children often        en after a positive trial. The pump itself,
first reported a trial of 20 patients in                respond well to ITB therapy because a           which is roughly the size of a thin hockey
1989 who received baclofen or placebo global reduction in tone can lead to an                          puck, is implanted into the anterior ab-
for three consecutive days followed by improvement in comfort, positioning,                            dominal wall in either the subcutaneous

360                                                                                                             PEDIATRIC ANNALS 35:5 | MAY 2006
space or in a subfacial location. Flexible
tubing runs subcutaneously around the            A
flank to the lumbar spine and into the

                                                 Average Ashworth Score
subarachnoid space. The tip of the intra-
thecal tubing is positioned under fluoro-

                                                        (± 2 SE)
scopic guidance at a spinal cord level as
determined by the pattern of spasticity
preoperatively (ie, higher placement of
the catheter if severe upper extremity
spasticity is present). The pump is pro-
grammed via a telemetry magnet on the                                     Baseline
skin directly over the pump, with the ini-                                               Follow-up Months
tial setting typically delivering around
50 micrograms per day. The dose can
be increased as the child recovers from
                                                 Average Ashworth Score

surgery in the hospital, and then in the
outpatient setting until the desired goal
                                                        (± 2 SE)

is achieved.
    The child should be monitored close-
ly after an ITB trial or pump placement,
as side effects including sedation, hy-
potonia, and respiratory depression can
result in rare circumstances. Refilling of
                                                                                         Follow-up Months
the pump is required every 2 to 6 months,
depending on the dose administered, and
                                             Figure 4. (A) Graph demonstrating the mean Ashworth scores in the lower extremities at 6-month
is done via a percutaneous injection, The    intervals after pump implantation. The scores were significantly decreased at 1 and 2 years post-im-
battery in the pump expires after seven      plantation (P < .005). (B) Graph demonstrating the mean Ashworth scores in the upper extremities at
                                             6-month intervals after pump implantation. The scores were decreased significantly at 1 and 2 years
years. The minimum weight require-           post-implantation (P < .005). (SE = standard error.)30
ment for a child to have an ITB pump is
approximately 10 kg.                         months. Lower-extremity and upper-ex-                 Awaad31 also reported on 29 patients
    Multiple clinical studies have dem-      tremity spasticity decreased significantly          with cerebral palsy with short-term fol-
onstrated that the majority of patients      in all patients. The side effects observed         low-up (48 months or less) after intra-
with ITB therapy have a significant de-       were mostly drug-related and included              thecal baclofen therapy. The outcome
crease in spasticity and some functional     temporary hypotonia, seizures, somno-              measures of spasticity as rated by the
improvement.30-33 The multicenter trial      lence, and nausea or vomiting.                     Ashworth scale and the caregiver assis-
that resulted in FDA approval was re-            In 2003, Albright30 reported a pro-            tance scales of the Pediatric Evaluation
ported in 2000 by Gilmartin et al.14 This    spective, multicenter study of 68 patients         of Disability Inventory (PEDI) were im-
study assessed the effectiveness of in-      with chronic intrathecal baclofen therapy          proved in all patients.
trathecal baclofen in reducing spasticity    who were followed closely for an aver-                The significant advantage of ITB
in cerebral palsy through an open-label      age of 70 months. The majority (76%) of            therapy is the adjustable and nondestruc-
trial of intrathecal baclofen administered   these patients were younger than 16 and            tive nature of the therapy. The amount of
through a chronic implanted pump. Can-       willing to participate in long-term sur-           drug delivery can be adjusted to meet the
didates were first screened with random-      veillance. Spasticity in both upper and            needs of each specific child. Because no
ized, double-blind, intrathecal injections   lower extremities decreased significantly           nervous tissue is destroyed, the effect of
of baclofen and placebo. Responders          and remained decreased throughout the              the therapy is reversible. The disadvan-
were defined as those who experienced         study period (Figure 4). The dosage of             tage, however, is that complications arise
an average reduction of one point in the     baclofen doubled on average during the             in some patients. Patients can be over-
lower extremities on the Ashworth Scale.     initial 2 years and then remained stable;          dosed with baclofen with subsequent
Ultimately, 44 patients received chronic     there were no significant differences with          hypotonia and lethargy, which usually
therapy and were observed for up to 43       dosage in children of different ages.              are managed with supportive care and

PEDIATRIC ANNALS 35:5 | MAY 2006                                                                                                           361
adjustments of the pump rate. Catheter                 6. Gooch JL, Oberg WA, Grams B, Ward LA,                  Child Neurol. 2002;44(1):17-25.
                                                          Walker ML. Care provider assessment of in-         22. McLaughlin JF, Bjornson KF, Astley SJ, et al.
migration, disconnection or fractures                     trathecal baclofen in children. Dev Med Child          Selective dorsal rhizotomy: efficacy and safety in
can occur, as well as other surgical prob-                Neurol. 2004;46(8):548-552.                            an investigator-masked randomized clinical trial.
lems such as seromas, cerebrospinal                    7. Ashworth B. Preliminary trial of cariso-               Dev Med Child Neurol. 1998;40(4):220-232.
                                                          prodol in multiple sclerosis. Practitioner.        23. Chicoine MR, Park TS, Kaufman BA. Selec-
fluid leaks, and infections.34
                                                          1964;192:540-542.                                      tive dorsal rhizotomy and rates of orthopedic
   Gooch et al. provided a retrospective               8. Bohannon RW, Smith MB. Interrater reliabil-            surgery in children with spastic cerebral palsy.
analysis of complications seen with ITB                   ity of a modified Ashworth scale of muscle              J Neurosurg. 1997;86(1):34-39.
therapy in the pediatric population. At 1                 spasticity. Phys Ther. 1987;67(2):206-207.         24. Greene WB, Dietz FR, Goldberg MJ, Gross
                                                       9. Watanabe T. The role of therapy in spastic-            RH, Miller F, Sussman MD. Rapid progres-
year, 24 patients (24%) within a group of                 ity management. Am J Phys Med Rehabil.                 sion of hip subluxation in cerebral palsy after
100 patients experienced 48 total com-                    2004;83(10 suppl):S45-S49.                             selective posterior rhizotomy. J Pediatr Or-
plications. The most common complica-                 10. Zafonte R, Lombard L, Elovic E. Antispastic-           thop. 1991;11(4):494-497.
                                                          ity medications: uses and limitations of enteral   25. Mooney JF 3rd, Millis MB. Spinal deformity
tions were catheter disconnection (9%),                   therapy. Am J Phys Med Rehabil. 2004;83(10             after selective dorsal rhizotomy in patients
catheter dislodgement (8%), pump site                     suppl):S50-S58.                                        with cerebral palsy. Clin Orthop Relat Res.
infection (4%), and cerebrospinal fluid in-            11. Koman LA, Mooney JF 3rd, Smith B, Goodman              1999 Jul;(364)48-52.
                                                          A, Mulvaney T. Management of cerebral palsy        26. Penn RD, Savoy SM, Corcos D, et al. Intra-
fection (1%).35 Also, if ITB therapy is dis-
                                                          with botulinum-A toxin: preliminary investiga-         thecal baclofen for severe spinal spasticity. N
continued abruptly, baclofen withdrawal                   tion. J Pediatr Orthop. 1993;13(4):489-495.            Engl J Med. 1989;320(23):1517-1521.
can occur, leading to rebound spasticity,             12. Gormley ME, Gaebler-Spira D, Delgado MR.           27. Coffey JR, Cahill D, Steers W, et al. Intrathe-
high fevers, and mental status changes.                   Use of botulinum toxin type A in pediatric pa-         cal baclofen for intractable spasticity of spi-
                                                          tients with cerebral palsy: a three-center ret-        nal origin: results of a long-term multicenter
                                                          rospective chart review. J Child Neurol. 2001;         study. J Neurosurg. 1993;78(2):226-232.
SUMMARY                                                   16(2):113-118.                                     28. Albright AL, Cervi A, Singletary J. Intrathe-
    The management of childhood spas-                 13. Baker R, Jasinski M, Maciag-Tymecka I, et              cal baclofen for spasticity in cerebral palsy.
                                                          al. Botulinum toxin treatment of spasticity in         JAMA. 1991;265(11):1418-1422.
ticity requires a multidisciplinary effort.               diplegic cerebral palsy: a randomized, double-     29. Middel B, Kuipers-Upmeijer H, Bouma J, et
With input from pediatricians, physical                   blind, placebo-controlled, dose-ranging study.         al. Effect of intrathecal baclofen delivered by
and occupational therapists, neurolo-                     Dev Med Child Neurol. 2002;44(10):666-675.             an implanted programmable pump on health
                                                      14. Corry IS, Cosgrove AP, Walsh EG, McClean               related quality of life in patients with severe
gists, orthotists, orthopedic surgeons,
                                                          D, Graham HK. Botulinum toxin A in the                 spasticity. J Neurol Neurosurg Psychiatry.
neurological surgeons, and other health-                  hemiplegic upper limb: a double-blind trial.           1997;63(2):204-209.
care personnel, effective treatment for                   Dev Med Child Neurol. 1997;39(3):185-193.          30. Albright AL, Gilmartin R, Swift D, et al.
spasticity can be initiated and maintained            15. Koman LA, Mooney JF 3rd, Smith BP,                     Long-term intrathecal baclofen therapy for
                                                          Walker F, Leon JM. Botulinum toxin type A              severe spasticity of cerebral origin. J Neuro-
that can lead to meaningful improve-                      neuromuscular blockade in the treatment of             surg. 2003;98(2):291-295.
ments in quality of life for vast numbers                 lower extremity spasticity in cerebral palsy: a    31. Awaad Y, Tayem H, Munoz S, et al. Function-
of children. Neurosurgical treatment of                   randomized, double-blind, placebo-controlled           al assessment following intrathecal baclofen
                                                          trial. BOTOX Study Group. J Pediatr Orthop.            therapy in children with spastic cerebral pal-
spasticity will continue to evolve and                    2000;20(1):108-115.                                    sy. J Child Neurol. 2003;18(1):26-34.
be refined as procedures and techniques                16. Sutherland DH, Kaufman KR, Wyatt MP,               32. Gilmartin R, Bruce D, Storrs BB, et al. Intra-
are appropriately evaluated with reliable                 Chambers HG, Mubarak SJ. Double-blind                  thecal baclofen for management of spastic ce-
                                                          study of botulinum A toxin injections into the         rebral palsy: multicenter trial. J Child Neurol.
and validated outcome measures.
                                                          gastrocnemius muscle in patients with cere-            2000;15(2):71-77.
                                                          bral palsy. Gait Posture. 1999;10(1):1-9.          33. Murphy NA, Irwin MC, Hoff C. Intrathecal
REFERENCES                                            17. Francisco GE. Botulinum toxin: dosing and              baclofen therapy in children with cerebral
 1. Koman LA, Smith BP, Shilt JS. Cerebral pal-           dilution. Am J Phys Med Rehabil. 2004;83(10            palsy: efficacy and complications. Arch Phys
    sy. Lancet. 2004;363(9421):1619-1631.                 suppl):S30-S37.                                        Med Rehabil. 2002;83(12):1721-1725.
 2. O’Shea TM, Preisser JS, Klinepeter KL, Dil-       18. Sindou M, Quoex C, Baleydier C. Fiber              34. Albright AL, Awaad Y, Muhonen M, et al.
    lard RG. Trends in mortality and cerebral palsy       organization at the posterior spinal cord-             Performance and complications associated
    in a geographically based cohort of very low          rootlet junction in man. J Comp Neurol.                with the synchromed 10-ml infusion pump
    birth weight neonates born between 1982 to            1974;153(1):15-26.                                     for intrathecal baclofen administration in chil-
    1994. Pediatrics. 1998;101(4 pt 1):642-647.       19. Fasano VA, Broggi G, Zeme S, Lo Russo G,               dren. J Neurosurg. 2004;101(1 suppl):64-68.
 3. Goldstein EM. Spasticity management: an               Sguazzi A. Long-term results of posterior          35. Gooch JL, Oberg WA, Grams B, Ward LA,
    overview. J Child Neurol. 2001;16(1):16-23.           functional rhizotomy. Acta Neurochir Suppl             Walker ML. Complications of intrathecal ba-
 4. Sanger TD, Delgado MR, Gaebler-Spira D,               (Wien). 1980;30:435-439.                               clofen pumps in children. Pediatr Neurosurg.
    Hallett M, Mink JW. Classification and defini-      20. Park TS, Owen JH. Surgical management of               2003;39(1):1-6.
    tion of disorders causing hypertonia in child-        spastic diplegia in cerebral palsy. N Engl J       36. Park TS, Gaffney PE, Kaufman BA, Molleston
    hood. Pediatrics. 2003;111(1):e89-e97.                Med. 1992;326(11):745-749.                             MC. Selective lumbosacral dorsal rhizotomy
 5. Flett PJ. Rehabilitation of spasticity and re-    21. McLaughlin J, Bjornson K, Temkin N, et al.             immediately caudal to the conus medullaris
    lated problems in childhood cerebral palsy. J         Selective dorsal rhizotomy: meta-analysis of           for cerebral palsy spasticity. Neurosurgery.
    Paediatr Child Health. 2003;39(1):6-14.               three randomized controlled trials. Dev Med            1993;33(5):929-933; discussion 933-944.

362                                                                                                                     PEDIATRIC ANNALS 35:5 | MAY 2006
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.