KEY POINTS Jean-Michel Gracies, MD, PhD; Elie Elovic, MD; John McGuire, MD; David Simpson, MD Local treatments Muscle & Nerve Supplement 6 1997 Rationale for Rating Spasticity Patients with damage to central motor path- ways often develop weakness associated with abnormal patterns of muscle activity in the paretic limbs and imbalance between some agonists and their overactive antago-
Traditional Pharmacological Treatments for Spasticity Part I:Local Treatments
Department of Neurology, Jean-Michel Gracies, MD, PhDThe Mount Sinai Medical Center, New York, NY.Center for Head Injuries, (Elie Elovic, MD), JFK JohnsonRehabilitation Institute, Edison, NJ. RehabilitationInstitute of Chicago, (John McGuire, MD), Chicago, IL.Departments of Neurology and Clinical Neurophysiology,(David Simpson, MD), The Mount Sinai Medical Center,New York, NY.
Correspondence to: Jean-Michel Gracies, Department ofNeurology, The Mount Sinai Medical Center, OneGustave L. Levy Place, New York, NY 10029
Jean-Michel Gracies, MD, PhD; Elie Elovic, MD; John McGuire, MD;
David Simpson, MD
I n t roduction: GeneralConsiderations in the Decisionto Treat Spasticity
Patients with damage to central motor path-ways often develop weakness associatedwith abnormal patterns of muscle activity inthe paretic limbs and imbalance betweensome agonists and their overactive antago-
n i s t s .1 Muscle overactivity may lead to con-t r a c t u res, abnormal postures, and pain.2One cause of muscle overactivity is spastici-t y, defined as a velocity-dependent incre a s ein stretch reflex activity.3 As discussed below,spasticity has long been treated with bothlocal anesthetic and chemoneurolytic agents.H o w e v e r, the decision to reduce spasticityby these or other means is contingent onfirst establishing that its reduction has thepotential to bring about functional impro v e-ments for the patient.
Rationale for Rating Spasticity
N e u rologists have long elaborated methodsto rate spasticity.4 , 5 H o w e v e r, it has neverbeen demonstrated that increased stre t c hreflex activity by itself is functionally dis-abling; indeed, several authors have arg u e dagainst this hypothesis.6 , 7 F u rt h e rm o re, it isnow accepted by many in the neuro l o g i c a lrehabilitation community that other factorsa re more disabling than spasticity itself,
K E Y P O I N T S
• Pathological
reaction to stretch
is likely to have
significant impact
on function
• Spasticity is the
only form
of muscle
overactivity
quantifiable at the
bedside
Local treatments Muscle & Nerve Supplement 6 1997S2
including co-contraction, permanent toniccontraction of muscles in the absence of anys t retch or volitional command (spastic dys-tonia), weakness associated with slowre c ruitment and de-re c ruitment of motorunits, and muscle shortening. Hence, onemay question the relevance of rating andt reating spasticity.6
F u rther insight into pathophysiology mayhelp justify careful assessment of spasticity.Rating spasticity could be functionally re l e-vant if spasticity reflected in part anenhanced motoneuronal activity that wouldact in facilitating the eff e rent path of thereflex. Indeed, increased alpha motoneu-ronal excitability would result not only inexaggerated stretch reflexes, but also exag-gerated responses to any input arriving atthe motoneuron. For example, it would alsoexaggerate other contraction responses ofperipheral origin, such as reflexes from cuta-neous or vegetative inputs, and inappro p r i-ate responses to misdirected descendinginputs, such as pathological co-contractions.C l i n i c a l l y, such exaggerated motor re s p o n s-es, re g a rdless of the input origin, are func-tionally disabling, and are commonlyo b s e rved in patients affected by lesions tothe central motor pathways. While physio-logical evidence does not exist as yet inpatients, animal models have also suggestedthat enhanced motoneuronal excitabilitydoes participate in the pathophysiology ofs p a s t i c i t y.8 If intensity of spasticity wasp roven to reflect, even part l y, enhancedm o t o n e u ronal excitability, this would defini-tively legitimize its rating as functionally re l-e v a n t .
So far, however, only indirect arg u m e n t spoint to functional consequences of anenhanced reaction to stretch per se. In pop-ulations of hemiplegic patients, it waso b s e rved that spasticity was correlated withthe degree of functional impairm e n t ,7 and itwas further demonstrated that unwanted co-contractions are directly facilitated by tonics t retch of the co-contracting muscle.9
Thus, we think it is reasonable to assumethat the degree of spasticity may at leasthelp predict the severity of other, potentiallym o re disabling types of muscle overactivity,such as unwanted antagonistic co-contrac-tion. Since these are more difficult to quan-tify than stretch reflexes on a routine basis,9it seems relevant to focus at least on assess-ing spasticity — and accurately monitoringits decre a s e4 — as an indicator of other,m o re verifiably disabling types of overactivi-ty and as the only quantifiable form of mus-cle overactivity at the bedside.
Spasticity: Only One Component ina Pathological Cascade
We saw that spasticity may only reflect oneof the three main factors which are dire c t l ydisabling in patients with central nerv o u ssystem (CNS) lesions: paresis; muscle over-activity in the broad sense of the term ,including unwanted co-contractions; andmuscle contracture. Furt h e rm o re, these fac-tors appear prior to spasticity in the naturalh i s t o ry of most cases (see Figure 1).
Experimental and clinical studies haveestablished that after any damage to the cen-tral motor pathways, contracture can takeplace within a few days if overactivity iss e v e re and not corre c t e d ,2,10,11 or if the mus-cle, overactive or not, is left immobilized ina shortened position.1 2 In the case of a cere-bral stroke, the first pathological factorsa ffecting muscles in the affected hemibodya re immobilization, due to paresis and toe n v i ronmental conditions (such as hospital-i z a t i o n ) ,1 3 and nonspastic overactivity, possi-bly resulting from basal gangliad y s f u n c t i o n .1 , 1 0 These two factors pro v o k ei n c reasing muscle contracture .2,12,13 D a t af rom animal re s e a rc h1 5 , 1 6 , 1 7 and more re c e n t l yf rom clinical and physiological studies inp a t i e n t s1 8 , 1 9 indicate that contracture part i c i-pates in the delayed generation of spasticity,in association with re a rrangements of spinalre a c t i v i t y.1 1 F i n a l l y, when a muscle is short-ened by contracture, a given change in joint
Pathophysiology of Impairment After a Central Nervous System Lesion
Damage to higher centers will affect the function of several descending pathways, among which is thecorticospinal tract involved with voluntary movement. The resulting immediate paralysis will leave someof the muscles immobilized in a shortened position, which will be the first cause of muscle shortening.Muscle shortening by itself may then be the first generator of spasticity.15-17
The damage to the descending pathways will also provoke an imbalance in spinal reactivity that willundergo rearrangements after a variable period of time. These rearrangements in spinal reactivity willresult in abnormal muscle contractions and abnormal reflex responses, some of which will meet theclassical definition of spasticity. Then, spasticity and other types of muscle overactivity will continue toaggravate contracture.40 Note the vicious cycle set up between contracture and spasticity. This recipro-cal potentiation has therapeutic implications: spasticity cannot be addressed without treating contrac-ture, and contracture cannot be addressed without treating all types of muscle overactivity.
Local treatments Muscle & Nerve Supplement 6 1997S4
angle will stretch muscle fibers re l a t i v e l ym o re than normal, thus evoking ani n c reased reflex re s p o n s e .
T h e re f o re, spasticity appears to be only thefinal link in the pathophysiological chaina ffecting movement in these patients, and itsd rug-mediated decrease in the absence ofe ffects further up the chain is an insuff i c i e n ta rgument to claim that such a drug is usefulfor patients with central damage. As quanti-tative assessment of nonspastic overactivityis difficult without sophisticated physiologi-cal equipment,9 evaluation of any tre a t m e n taimed at correcting abnormalities of move-ment in patients with spasticity must at leastinclude, in addition to spasticity grading,m e a s u rement of muscle shortening (passiverange of motion), qualitative assessment ofdisabling co-contractions, active range ofmotion, and ratings of function that are asre p roducible and sensitive as possible. Thent reatment of spasticity is really monitoringof spasticity after treatment of muscle over-a c t i v i t y.
Treatment Strategy
B e f o re consideration of pharm a c o l o g i c a ltherapies, any peripheral cause of aggravat-ed muscle overactivity re q u i res tre a t m e n t .Such aggravation may be a consequence ofthe stimulation of aff e rents other than thes t retch receptors, such as flexor reflex aff e r-e n t s .1 9 a Examples include heterotopic ossifi-cation, urinary tract infection, uro l i t h i a s i s ,stool impaction, pre s s u re sore, fracture, dis-location, ingrown toenail, excessivelyrestrictive clothing, or condom drainageappliance. These factors should be tre a t e db e f o re any pharmacologic management ofmuscle overactivity.
Treatment of muscle overactivity is appro-priate only in those patients who are dis-abled by muscle overactivity or may becomedisabled by its main consequence: muscles h o rtening. It is a pre requisite to ensure thatoveractivity in a given muscle group is more
disabling than helpful. Muscle overactivityf rom lesions in the central motor pathwaysis difficult to tre a t .2 0 Available tre a t m e n t sinvolve physical methods and chemicalsa d m i n i s t e red systemically, regionally orl o c a l l y. In a number of common pathologies,such as stroke or traumatic brain injury,muscle overactivity is not equally spre a dt h roughout the body and predominates onlyin certain muscle groups. For example inthe upper limb of hemiplegic patients, over-activity usually affects flexors andp ro n a t o r s .1 In these cases the logical andoften more re w a rding approach is to uselocal treatments. In other conditions, suchas multiple sclerosis or spinal cord injury, inwhich the distribution of spasticity may bem o re diffuse, regional or systemic tre a t-ments may be pre f e r a b l e .
Physical Tre a t m e n t s
Since muscle shortening increases spindlesensitivity and spasticity,1 5 , 1 6 , 1 7 muscle con-t r a c t u re and muscle overactivity are inter-twined. There f o re, physical tre a t m e n t saimed at lengthening overactive muscles orat maintaining their length are part of localt reatment of spasticity.1 3 Optimal efficacy ofany “antispasticity” therapy re q u i res thatboth abnormalities be addressed simultane-ously: a chemical treatment to relax a mus-cle is combined with a physical treatment tolengthen the muscle.
The mainstay of physical treatment is mus-cle stretch, as early as possible, to pre v e n tmuscle short e n i n g .1 3 Physical therapy ses-sions commonly involve passive range ofmotion exercises or short posturing sessions.H o w e v e r, to prevent contractures in thelong term, muscle stretch is probably moste fficient when applied continuously for sev-eral hours each day.2 1 Rigid or semi-rigiddevices, including serial rigid splints, serialcasts, and dynamic splints, are helpful forthis purpose.1 8 , 2 2 , 2 3 Positioning techniquesand weight-bearing activities can also beused. The efficacy of prolonged daily mus-
cle stretch is greater when applied to re l a x e dmuscles. Before the emergence of botulinumtoxin, two types of compounds were used top rovide local muscle relaxation: local anes-thetics (lidocaine and congeners), with afully reversible action of short duration, andalcohols, chiefly ethyl alcohol (ethanol) andphenyl alcohol (phenol), with a longer dura-tion of action. This review discusses theseclassical chemical local treatments, theirphysiological action, pharm a c o l o g y, risks,and indications (see Tables 1 and 2). In theabsence of controlled studies evaluating tra-ditional neurolytic therapy vs. botulinumtoxin, we propose a theoretical comparisonof both methods in the final section.
Local Anesthetic Agents
Lidocaine, etidocaine, and bupivacaine arec u rrently the pre f e rred local anesthetics forrelaxation of overactive muscles or in physi-ological re s e a rc h .4 5 , 4 8 , 4 9 , 2 7 They have re p l a c e dp rocaine, which was first synthesized in1905 and was in common use up to the1 9 7 0 s .3 0 , 3 1 , 3 3 , 3 5
In 1919, Liljestrand and Magnus2 4 re p o rt e dthat intramuscular injection of pro c a i n ereduced the triceps rigidity of a decere b r a t ecat. However, this fundamental observ a t i o nwas published at a time when most of thescientific community still accepted theresponse of a muscle to its own stretch as anintrinsic muscle pro p e rt y, and not as a re f l e xmediated through neurons in the centraln e rvous system. That demonstration onlycame 5 years later with Liddell andS h e rr i n g t o n .25 I n t e rest in the observations ofLiljestrand and Magnus, and their implica-tions for therapy, finally emerged more than40 years after that, following another majorstep in the understanding of stretch re f l e x e s :the elucidation of the role of the gammam o t o n e u ro n s .2 6
Definition and Physiology
Local anesthetics are drugs that block nerv econduction when applied locally to nerv etissue in appropriate concentrations, andwhose action is reversible without causings t ructural damage to nerve fibers or cells.2 7
The conduction block decreases or pre v e n t sthe large transient increase in the membranep e rmeability to sodium ions, which is nor-mally produced by a slight depolarization ofthe membrane, especially at the nodalregions. Local anesthetics act on peripheraland central neuro n s .2 8 A local anesthetic incontact with a peripheal nerve trunk causesboth sensory and motor paralysis in thei n n e rvated area. Since ionic mechanisms ofexcitability are similar in nerve and muscle,these agents also act on all types of muscu-lar tissue. However, several physiologicalprinciples determine diff e rences in the rateand scale of the clinical effects on the diff e r-ent affected tissue types:
Slight diff e rences in the sensitivity of diff e re n tfiber types to local anesthetics2 7
As a general rule, small nerve fibers arem o re rapidly blocked than large nerv efibers, as was first shown by Gasser andE r l a n g e r.29 In 1957, Matthews andR u s h w o rth re p o rted that muscle pro p r i o-ceptive aff e rent and muscle eff e rent fibers,which are of the same diameter, were equal-ly sensitive to pro c a i n e .3 0 H o w e v e r, thesmaller gamma fibers supplying the musclespindles were more rapidly blocked by thelocal anesthetic. Franz and Perry suggestedthat this might be due to the shorter inter-nodal distance of smaller axons, since morenodes would be immediately accessible tothe local anesthetic, whereas larger axonswould re q u i re more time for the anestheticto diffuse to an equivalent number ofn o d e s .3 1 The same might account for theslower re c o v e ry of small axons at reversal ofthe process. This “faster” block of thegamma fibers caused some confusion in then e u ro l o g i c a l3 2 , 3 3 , 3 4 and physiological3 5 l i t e r a -
Local treatments Muscle & Nerve Supplement 6 1997S6
Local treatments Muscle & Nerve Supplement 6 1997S8
tion block on muscle aff e rents and eff e re n t shas not been examined. If gre a t e r, one mayspeculate that a threshold dose of local anes-thetic could be used as a short - t e rm mimicof botulinum toxin, allowing the clinician top review the effects of neuromuscular blockin order to estimate the value of undert a k-ing botulinum toxin injections.
P h a rmacology and Risks
Onset of actionWhen a local anesthetic is injected close to aperipheral nerve, its onset of action occurswithin minutes (3 minutes for lidocaine, 15minutes for bupivacaine). The delay of onsetis greater when there is a need for diff u s i o nof the agent from its site of injection to itssite of action, for example, when a nerv eplexus is blocked (the delay of onset of thee ffect of lidocaine injected about thebrachial plexus goes up to 15 minutes).27
Duration of actionThe duration of action of a local anestheticdepends primarily on the lipid solubilityand the protein binding affinity of the anes-thetic. It is also pro p o rtional to the timeduring which the anesthetic is in actual con-tact with nervous tissues and inversely re l a t-ed to the regional blood flow of the injecteds i t e .4 4 C o n s e q u e n t l y, pro c e d u res that keepthe drug at the nerve by reducing localblood flow prolong the period of anesthesia.This also helps reduce its systemic toxicityby slowing its absorption into the circ u l a-tion. There f o re, in clinical practice, the solu-tion of a local anesthetic usually also con-tains vasoconstrictors: epinephrine or a suit-able synthetic congener, norepinephrine orphenylephrine. However, because of thepossibly intense vasoconstriction, epineph-rine-containing solutions should not beinjected into tissues supplied by end art e r-ies, such as fingers and toes.
R i s k sThe risks described below re q u i re thatresuscitation equipment and personnel
K E Y P O I N T S
• Local anesthetics
act by transiently
blocking the
sodium channels
of motor and
sensory nerves,
the
neuromuscular
junction, and
muscle
t u re of the 1960s, with several works re -lying on the erroneous belief of “exclusive”gamma block with local anesthetics. Thesame confusion appeared re g a rding thep ro p e rties of alcohol and phenol3 2 , 3 3 , 3 4 ( s e eb e l o w ) .
D i ff e rences in sensitivity according to impulsetransmission characteristics2 7
F requency and pattern of nerve impulsetransmission also determine the types ofn e rve that are primarily affected, pro b a b l yby varying the durations of the open statesof sodium channels. For instance, etidocainehas been re p o rted to block somatic motorn e rves more than somatic sensory fibers.3 6
Indeed, the firing frequency of motor neu-rons rarely surpasses 10 Hz, in both norm a lsubjects and hemiplegic patients. In con-trast, the frequency of muscle spindle aff e r-ents is about 15 to 20 Hz within interm e d i-ate ranges of static muscle stretch, and cango up to more than 40 Hz during a dynamics t retch or a contraction, as measured inm i c ro n e u rographic experiments in norm a ls u b j e c t s3 7 and hemiplegic patients.3 8
Recent firing history of the nerv eThe degree of block produced by a givenconcentration of local anesthetic depends onhow much and how recently the nerve hasbeen stimulated.2 7 Thus, a resting or nor-moactive nerve is much less sensitive to alocal anesthetic than one that has beenrecently and repetitively stimulated.4 2
T h e re f o re, a local anesthetic can be expectedto have greater efficacy on the overactivemuscles that are the target of therapy, and asmaller paralyzing effect on normally activemuscles that the anesthetic has reached byd i ffusion. A similar phenomenon has beensuggested with botulinum toxin.4 3
E ffects at the neuromuscular junctionLocal anesthetics also affect transmission atthe neuromuscular junction39,40 by a mecha-nism that is yet to be clarified.4 1 To ourknowledge, the question of whether thise ffect is greater or weaker than the conduc-
trained in the management of acute car-d i o p u l m o n a ry emergencies be immediatelyavailable when local anesthetic is infiltratedinto a tissue.
Toxic systemic effects: If local anestheticsi n a d v e rtently enter the systemic circ u l a t i o n ,they will interf e re with the function of allo rgans in which conduction or transmissionof impulses occur.
Central nervous system effects begin withcentral stimulation, including re s t l e s s n e s sand tremor that may proceed to convul-sions. The mechanism responsible for thesee ffects has not yet been clarified.Benzodiazepines may be used to treat thiscentral stimulation. Stimulation effects arefollowed by CNS depression, and death canoccur due to re s p i r a t o ry failure .27
The cardiovascular system is usually aff e c t e dat higher systemic concentrations than thecentral nervous system. Local anestheticsinjected systemically have a spasmolyticaction on smooth muscle and most causea rteriolar dilatation (though cocaine doesn o t2 7), likely due to a decrease in sympathet-ic nerve eff e rent activity.2 7 T h e re f o re, ad e c rease in arterial pre s s u re is possible, aswas shown with lidocaine in animal experi-m e n t s .4 5 When lidocaine has been injectedat high doses in patients (100 mg intra-venously plus 300 mg intramuscularly), ithas been associated with sudden card i a cc o l l a p s e .4 6 In the heart, local anesthetics actprimarily in the myocardium, in decre a s i n ge x c i t a b i l i t y, conduction rate, and force ofcontraction, similar to quinidine. (For thesereasons, lidocaine is commonly used to pre-vent ventricular fibrillation at the initialphase of an acute myocardial infarc t i o n .4 6)
Hypersensitivity: This major adverse eff e c tr a rely occurs; when it does, it may take thef o rm of an allergic rash or a fatal anaphylac-tic re a c t i o n .2 7 , 4 0 It is encountered most oftenwith local anesthetics of the ester type(cocaine, procaine, tetracaine).
P recaution in liver insufficiency: Most of themetabolism of local anesthetics occurs in theliver (especially for lidocaine) and the exten-sive use of a local anesthetic in patients withs e v e re hepatic damage should be avoided.2 7
Neural toxicity: Animal experiments suggestthat local anesthetics also carry a low risk ofneural toxicity after perineural injection,which is pro p o rtional to the concentrationused and to the conduction blocking poten-cy of the compound.4 7
Choice of the Local Anesthetic
T h e re are a large number of synthetic localanesthetics. They differ by their delay andduration of action, anesthetic power, andassociated risks.2 7 Local anesthetics may bedivided into three categories by their dura-tion of action: short (20 to 45 minutes) suchas procaine, intermediate (1 to 3 hours)such as lidocaine and prilocaine, and long(several hours) such as tetracaine, etido-caine, and bupivacaine. Duration incre a s e swith the amount of drug injected, but sodoes the risk of systemic toxic re a c t i o n s .T h e re f o re, duration of action is more safelyp rolonged by the addition of epinephrine(see above).27 As noted above, lidocaine, eti-docaine, and bupivacaine are now generallyp re f e rred over pro c a i n e .
Lidocaine produces more prompt, intense,long-lasting, and extensive anesthesia thandoes an equal amount of pro c a i n e .5 0 , 2 7
Unlike procaine, which is an ester, lidocaineis an aminoethylamide and, there f o re, hasless propensity to provoke reactions ofh y p e r s e n s i t i v i t y.2 7 Systemic side effects char-acteristic of lidocaine include sedation anddizziness. Lidocaine is available as lidocaineh y d rochloride (Lignocaine®, Xylocaine®,others) in dilutions from 0.5% to 4%, withor without epinephrine (1:200,000; 5µ/mL),which can double the duration of eff e c t .2 7
Dilutions of lidocaine used for infiltrationsand blocks are usually between 0.5% and2 % .4 8 , 4 9 When used without epinephrine, up
K E Y P O I N T S
• Use of local
anesthetics
require
resuscitation
equipment and
trained personnel
available close by
Local treatments Muscle & Nerve Supplement 6 1997S10
to 7 mg/kg of 0.5 to 2% lidocaine solution(0.7 mL/kg for a 1% solution) can be usedfor nerve block or infiltration anesthesia.2 7
Etidocaine (Duranest®) and bupivacaineh y d rochloride (Marc a i n e®) are now pre-f e rred by many rehabilitation teams for testsof muscle relaxation because their durationof action is greater than that of lidocaine.Bupivacaine is also more potent than lido-caine and can be used in amounts up to 3mg/kg of 0.25 to 0.75% solution.2 7
Bupivacaine may be pre f e rred to lidocaineespecially to determine if functionali m p rovement may result from long-termc h e m o d e n e rvation, since its longer durationof action may allow more thorough assess-ment during the anesthetic period.Etidocaine is favored by some clinicians forits propensity to block motor fibers morethan sensory fibers.3 6 Its effects last 2-3times as long as lidocaine, with about thesame induction time. Etidocaine is availablein 0.5% and 1.0% solution with or withoutepinephrine, and in 1.5% solution with epi-nephrine (1:200,000; 5 µ/mL). The maxi-mum dose is 6 mg/kg without epinephrineand 8 mg/kg with epinephrine.
Technical Issues For Use in Patientswith Muscle Overactivity
Both intramuscular and perineural blocksmay be useful.
Intramuscular local anesthesiaThe maximum effect of an intramuscularblock may be obtained when the drug isinjected within the target muscle in thevicinity of the neuromuscular junctions,5 1
which is consistent with the known sensitiv-ity of neuromuscular junctions to local anes-t h e t i c s .3 9 , 4 0 , 4 1 Intramuscular blocks arere p o rted to be more painful than nerv eblocks at proximal branches or sensorimotort ru n k s .5 2 L a rger volumes of anesthetici n c rease the likelihood of spread of the solu-tion to nearby muscles or other stru c t u re s( n e rve trunks) that one may not wish toa ff e c t .2 7
N e rve block anesthesiaA mixed peripheral nerve consists of indi-vidual nerve fascicles surrounded by anepineurium. The vascular supply is usuallycentrally located. When a local anesthetic isinjected near a peripheral nerve, it diff u s e sf rom the outer surface toward the coredown its concentration gradient, blockingfirst the nerve fibers located in the outermantle of the trunk. These fibers usuallyi n n e rvate more proximal anatomical stru c-t u res than those situated near the core. Theduration of their blockade is also longerthan for central fibers because the vascularuptake of the anesthetic usually occurs pri-marily in the core of the mixed nerve.
For both intramuscular and nerve blocktechniques, the rigorous way of pro c e e d i n gis to use an exploratory stimulation tech-nique, as for botulinum toxin.5 1 The sameneedle that will inject the drug is used totransmit repetitive monopolar stimulation ofthe targeted nerve or muscle in order toadjust its position. The tip of the needle isd i rected as close as possible to the nerv et runk by searching for the minimal stimula-tion re q u i red to elicit the appropriate pare s-thesia or muscle twitches. Similarly, it willlie selectively in the targeted muscle whenthe best bulk of twitch, as assessed clinically,is obtained in isolation by the minimal pos-sible stimulation. For the most precise local-ization among muscles, the stimulation are amust be as small as possible. There f o re ,pulse widths must be as short as possible(0.2-0.5 ms), and needles of small caliber(27G) should be used. These needles arecommonly used for botulinum toxin injec-tions and are rigid enough to penetrate evendeep limb muscles.
Indications: Diagnostic Pro c e d u re sand Therapeutic Tests
Intramuscular local anesthesia (lidocaine,etidocaine, bupivacaine) has long been usedas a diagnostic tool.53 The short duration ofe ffect of local anesthetic blocks makes themuseful as temporary tests, before providing along-lasting treatment. A local anestheticblock can help answer a number of ques-tions, not only about therapeutic indicationsbut also about the mechanisms involved inthe functional impairm e n t :
P rediction of functional changes with long-termt h e r a p yThe fundamental therapeutic questionwhich justifies a short - t e rm block is whethera long-term block of the same muscle orn e rve could be functionally useful. Toa d d ress this question, objective means offunctional assessment must be designedb e f o re the block. The answer to this thera-peutic issue provides insight into the mech-anisms involved in the functional impair-ment.
Understanding of impairment mechanismsR e g a rding the mechanisms of impairment inpatients with muscle overactivity, it is notyet known whether the block must be pow-e rful enough to significantly weaken theinjected muscle, or whether merely re d u c i n gits reflex reactions to stretch is suff i c i e n t .Indeed, the experience of authors usingalcohol and phenol injections (see below) aswell as recent studies with botulinumt o x i n5 4 suggest that, re g a rdless of the para-lyzing agent, significant weakening of theinjected muscle may be re q u i red to allowe x p ression of antagonists in spastic patients.The mechanistic questions that a local anes-thetic block may help answer include:
(i) What are the roles played by overactivityand contracture in the impairment of func-tion? By only temporarily paralyzing a mus-cle without lengthening it, the block mayallow the investigator to determine the re l a-tive contributions of overactivity and ofmuscle shortening in the generation of thepathologic posture.
(ii) Which muscle or muscles are contribut-ing to the pathologic posture? The exampleof foot inversion during gait may illustratethis question. As Glenn points out,5 2 it islogical to assume that in some cases of footinversion during swing phase of gait in aspastic patient, the deformity results fro mthe inability of the tibialis anterior to over-come overactive or contractured plantarf l e x-ors, so that all of its contractile force attractsthe foot towards inversion rather than dorsi-flexion. In such cases, nerve blocks of purep l a n t a rflexors (soleus and gastro c n e m i i )could confirm this hypothesis by impro v i n gfoot posture if the resistance from thesemuscles is due to overactivity and not tos h o rtening. In other cases, inversion duringswing phase is due to overactivity of the tib-ialis posterior, and blocking this muscle mayhelp confirm this diagnosis.
(iii) What is the level of active perf o rm a n c eof the antagonistic muscles once they aref ree of opposing co-contraction? One mayonly answer this question if the short e n i n gof the injected muscle is not severe enoughto block the range of movement of theantagonists (see preceding question).
(iv) What are the contributions of spasticityand contractures in the resistance to stre t c h ?This is a more technical question relating tothe interpretation of the clinical examina-tion. It is overlooked by any rating scale thatassesses both active and passive tissue re a c -tion by only examining its subjective severi-ty (minimal, more marked, considerable)5
instead of assessing its type (existence of ac a t c h - a n d - release or a clonus, fatiguable ornot, which are specifically produced bymuscle contractions in reaction to stre t c h ,and not by passive tissue).4
K E Y P O IN T S
• In a patient with
focal overactivity,
use of a block
with local
anesthetic may
help answer
whether a long
lasting block
could be
functionally useful
Local treatments Muscle & Nerve Supplement 6 1997S12
Other Uses of Local Anesthetics inOveractive Muscles
Local anesthetic blocks have also been usedas preparation for casting (plaster or fiber-glass) to prevent contracture s .5 2 Placing thee x t remity in a cast soon after the block wills t retch the relaxed muscle, which mayinhibit the re t u rn of overactivity and helpi m p rove the efficacy and tolerability of thecast. However, forceful overactivity mayre t u rn within the cast so that usually theangle of the cast is adjusted at only 50% ofthe gain in passive range of motion obtainedf rom the block. To prevent complicationssuch as skin breakdown, the limb in thecast must be carefully monitore d .
F i n a l l y, lidocaine can serve as an analgesicfor intramuscular injection pro c e d u res whenmixed with the medication to be injected. Ithas been demonstrated to reduce the painassociated with intramuscular injection ofa n t i b i o t i c s ,5 5 at the time after the injectionand at intervals of 10 minutes, 20 minutes,and 6 hours. A similar demonstration forprilocaine has been done with intramuscularinjections of propofol, an anesthetic.5 6
Authors have used lidocaine for this anal-gesic indication when injecting alcohol intom u s c l e s ,5 7 , 4 8 , 5 8 and for steroid injectiona round nerves or epidurally.5 9 , 6 0 , 6 1 H o w e v e r,in the studies with propofol injections, itwas observed that this compound wasre q u i red in greater amounts when mixedwith prilocaine than when mixed withsaline. A binding between the algesic part ofthe propofol molecule and the local anes-thetic agent has been postulated to explainthis findings.5 6 This possibility should bec o n s i d e red when using lidocaine mixedwith alcohol.4 8
Local Anesthetics: Summary
Local anesthetics block both aff e rent ande ff e rent messages in a muscle. Their usere q u i res available resuscitation equipment.When a long-lasting blocking agent is beingc o n s i d e red, a temporary block with a localanesthetic may be useful to assess the mech-anisms of functional impairment and to helpp redict what improvement may be expected. In order to answer these questions, theblock may have to provoke a measurableweakening in voluntary power of the targ e t-ed muscles since co-contraction, a phenom-enon of primarily descending origin,9 is like-ly to play a major role in the functionali m p a i rment of patients with damage to thecentral motor pathways.
Blocks Acting by Stru c t u r a lDamage: Alcohol and Phenol
Chemical Neurolysis in Spasticity
G l e n n5 2 has defined a nerve block as “theapplication of chemical agents to a nerve toi m p a i r, either temporarily or perm a n e n t l y,the conduction along the nerve,” whilechemical neurolysis “is a nerve block thatimpairs nerve conduction by means ofd e s t ruction of a portion of the nerve.”
Initial re p o rts of chemical neurolysis used aslocal or regional treatment of muscle overac-tivity involved injections of 2% to 5% car-bolic acid (phenol) intrathecally,62,63,34 p e r i -n e u r a l l y,64 and intramuscularly,6 5 and of 35%to 45% ethyl alcohol (ethanol), epidurally,6 6
i n t r a m u s c u l a r l y,5 7 and perineurally.6 7 , 3 2 A swith local anesthetic blocks, these pioneer-ing experiences were encouraged by thespeculation that phenol and alcohol wouldselectively affect small diameter fibers.3 2 , 3 3 , 3 4
H o w e v e r, this was later shown to be incor-re c t .6 8 While Ta rdieu perf o rmed two con-t rolled studies of chemical neuro l y s i s ,6 9 , 7 0 t h el i t e r a t u re contains mostly anecdotal re p o rts.
These have indicated that spasticity isrelieved following these treatments, withe ffects lasting from months to years.5 1 , 5 2
Intrathecal neurolysis is now rarely used,but the effects of selective perineural neuro l -ysis are still re p o rted sporadically.5 2 , 7 1
Injections can be made close to a nerv et runk (perineural), called “mixed sensorimo-tor nerve blocks,” or into the muscle at themotor point, called “motor nerve blocks”5 2
or “neuromuscular blocks.”5 1 P e r i n e u r a linjections are considered easier and moree ffective than intramuscular ones and areusually pre f e rred for proximal muscles orwhen several muscles are to be injected inthe same nerve terr i t o ry. For example, peri-neural injections can be used for tre a t i n gspasticity in muscle groups that are other-wise inaccessible, such as iliopsoas, quadra-tus lumborum, or paraspinals6 6 (see below).
Alcohol Injections
Ethyl alcohol (“alcohol” hereafter) was thefirst alcohol compound to be studied exper-imentally on nerve cells,7 2 , 7 3 the first used forn e u romuscular block,6 6 , 6 9 and the only oneassessed in controlled protocols for thisi n d i c a t i o n .6 9 , 7 0 Despite a better safety re c o rdthan phenol (see below), alcohol has notbeen used as extensively for the treatment ofs p a s t i c i t y.5 2 Local injections of alcohol wereused by neurologists for sympathectomy(lumbar paravertebral injections) and for thet reatment of pain (trigeminal neuralgia,intractable carcinoma using paraganglionicand plexus injections)74 prior to its use ins p a s t i c i t y. We review here its mechanisms ofaction based on animal re s e a rch, and itsrisks, results, and indications in patients.
Histological and physiological eff e c t sPerineural injections: At low concentrations(5% to 10%), alcohol acts as a local anes-thetic by decreasing sodium and potassiumconductance; at higher concentrations, alco-hol nonselectively denatures proteins andi n j u res cells by precipitating and dehydrat-
ing pro t o p l a s m .7 4 In 1912, May showed inanimals that absolute alcohol causes degen-eration of neurons with extensive fibro s i sand partial re g e n e r a t i o n .7 2 At lower concen-trations, axonal destruction was inconstant.F u n c t i o n a l l y, there was always full re c o v e ryof paralysis, and with 50% alcohol, noweakness was seen. Gordon studied 80%alcohol, producing various degrees of neu-ronal degeneration and surro u n d i n gf i b ro s i s .7 3 Functionally these injectionscaused some degree of weakness withoutcomplete paralysis. Labat, using 48% and95% alcohol in dogs, also provoked a tem-p o r a ry paralysis with both concentrationslasting usually less than 2 months,7 5 w h i c hwas not correlated with the concentrationused.
Ta rdieu et al. applied 35% alcohol into oneposterior tibial nerve of healthy cats, withthe other side left untre a t e d .69,70 The catsw e re first observed for several weeks: Theywalked, ran, and jumped normally despitethe block. A midcollicular section was thenp e rf o rmed for decerebration. Despite thep re s e rvation of strength in the “blocked” legb e f o re decerebration, there was a diminu-tion of spasticity after decerebration re s u l t-ing from the nerve block. Furt h e rm o re, ten-sion produced by the stretch reflex wasreduced, while tension produced by stimu-lation of the tibial nerve was not.Histological analyses were perf o rmed 3weeks after application of alcohol. On theinjected side, there were lesions in themyelin, mostly in small fibers, with noaxonal damage.6 9 Cholinesterase activity inthe endplates of the muscle spindles wasreduced on the injected side only. Theauthors did not find any abnormality in thecholinesterase activity in the extrafusalfibers. Clinically, voluntary movement wasn o rmal. Ta rdieu felt that these findingsf a v o red a selective effect of 35% alcohol onsmall diameter gamma motor neuro n s .C o n v e r s e l y, Fisher et al. studied the evokedresponse of fibers injected with 35% to 47%alcohol soon after exposure and found that
Local treatments Muscle & Nerve Supplement 6 1997S14
Vascular complications: O’Hanlan et al. initial-ly re p o rted several cases of phlebitis, whichthey ascribed to a poor preparation of thealcohol (“state store” alcohol). Theyo b s e rved no phlebitis when alcohol wasp re p a red in a pharm a c y.8 4 A case of transientspinal ischemia following a deep plexusalcohol injection has also been re p o rt e d .8 5
P e rmanent peripheral nerve palsy: This hasbeen re p o rted for obturator or pero n e a ln e rv e s .5 1 , 5 2
Skin irritation: This may be secondary tos u p e rficial injection. Skin torpid ulcerationshave also been re p o rted after alcoholizationof peripheral fibers.8 6
Systemic eff e c t s : Patients may exhibit sys-temic signs and symptoms of intoxication inthe immediate postinjection period.5 1
Painful muscle necrosis: At least one case hasbeen re p o rted when using alcohol concen-trated beyond 75%.8 7
Motor nerve blocks in spasticity: clinical re s u l t sand indicationsIn the early 1960s, Ta rdieu and colleaguesinitially proposed injection of a local chemi-cal neurolytic compound directly into mus-c l e .6 6 , 5 7 , 6 9 They injected 45% alcohol intomuscles at the motor point in children withc e rebral palsy and re p o rted that spasticitywas reduced in most cases without aff e c t i n gv o l u n t a ry strength. The effect lasted from 6to 12 months and occasionally as long as 2to 3 years.66,57,69,70 The treatment was thenstudied by other authors,84,88,53,78,89 and somemodifications in the technique were pro-p o s e d .1 0 9 , 1 9 , 2 0 O ’ H a n l a n1 0 9 used the samedilution of alcohol but did not try to targ e tthe motor nerves specifically. He injectedl a rge quantities of 45% alcohol (between 10and 40 mL according to the muscle) intomultiple locations within the target musclesof spastic patients. Like Ta rdieu, O’Hanlanfound a significant reduction of spasticity inthe 10 cases re p o rted with no loss of volun-
the injection had a nonselective effect on theresponses of fibers of various diameters.7 6
Intramuscular injections: When absolute alco-hol is injected at doses up to 10 mL/kg intomuscle in the hind leg of rats, there is alocal dose-dependent coagulation necro s i sfollowed by granulation tissue form a t i o nand subsequent fibro s i s .7 7 Biopsies of sitesp reviously injected with 45% alcohol havedemonstrated muscle necrosis and inflam-m a t o ry cells within the damaged are a s .7 8 A tlower concentrations, from 20% to 40%,alcohol has still been demonstrated to bemyotoxic in animals7 7 , 7 9 with creatine kinaserelease being inhibited by adjunction ofdibucaine, a very potent local anesthetic.7 9
The destructive effect of alcohol on tissuehas led some authors to propose absolutealcohol as a local antitumoral treatment bytopical injection for cancer,8 0 in thyroid orp a r a t h y roid nodules,8 1 , 8 2 or as sclero t h e r a p yfor venous malform a t i o n s .8 3
Adverse eff e c t sT h e re have been relatively few re p o rts ofadverse effects of intramuscular and peri-neural alcohol injections as compared tophenol. This may correspond to gre a t e rsafety of alcohol or to the fact that phenolhas been used more extensively in the lastt h ree decades, with pro p o rtionately morere p o rts of adverse events using this com-pound. The adverse effects of alcohol injec-tion include:
Pain at injection: Ethyl alcohol injected intra-muscularly is painful, such that some sug-gest conscious sedation or general anesthe-s i a .5 1 Carpenter has re p o rted complicationsincluding burning sensation of the muscleand local hyperemia usually lasting less than36 hours.53,78
t a ry motor power. Sensation was alsore p o rted to remain intact.8 4
Carpenter and Seitz, using 45% to 50%alcohol, popularized this technique underthe name “intramuscular alcohol wash.”5 3 , 7 8
The pro c e d u re was perf o rmed under generalanesthesia because of the local pain duringinjection. These authors obtained their bestresults with gastrocnemius muscle injec-ions. The muscle was divided into quad-rants and 2 to 6 mL of alcohol were injectedinto each quadrant. The authors claimedthat the treatment eliminated the equinusgait in 128 of 130 children injected. Resultsf rom injections into other muscles were notas consistently good. However, the durationof effect was shorter than that re p o rted byTa rdieu et al., with a re t u rn of equinus pos-t u re 7 to 20 days after the gastro c n e m i u sinjections. Overall, the effects lasted onlyf rom 1 to 6 weeks. Muscle biopsies per-f o rmed in 6 patients 4 to 6 weeks after theinjection revealed a round cell infiltratewithout fibrosis.
Other indications in intramuscular injectionsOther indications in intramuscular injec-tions are currently expanding, and thisshould encourage clinicians to consideralcohol more often for muscle overactivityin spastic conditions. Alcohol has re c e n t l ybeen proposed in association with 0.5%lidocaine, in repeated injections as localt reatment of dystonia (10% dilution)4 8 o rspasmodic torticollis (99% dilution).5 8 I t slesional effects on muscular tissue have alsobeen exploited to damage the “re e n t ry cir-cuits” characteristic of Wo l ff - P a r k i n s o n -White syndrome; intracardiac injections ofabsolute alcohol for this indication havebeen studied in animals9 0 and used inp a t i e n t s .9 1 , 9 2
Dilutions usedThe most common alcohol dilution rangeused in spasticity until recently has been35% to 60%.6 6 , 8 4 , 8 9H o w e v e r, some now useweaker concentrations in children withs p a s t i c i t y.8 7 For some forms of dystonia, Kajirecently re p o rted the use of alcohol dilutedto 10%, mixed with 0.5 % lidocaine inject-ed intramuscularly.4 8
Conclusion: alcohol for chemoneuro l y s i sIn intramuscular injections, alcohol dilutedat 45% or lower seems relatively safe,although it acts by destruction of muscle.Alcohol appears to be more efficient wheninjected close to the motor point. Little hasbeen re p o rted on the use of alcohol in peri-neural injections.3 2 , 6 7 Clinical contro l l e dstudies are re q u i red to assess its value com-p a red to phenol and to botulinum toxin.
Phenol Injections
Phenol (benzyl alcohol) is the major oxi-dized metabolite of benzene, a knownhuman leukemogen and ubiquitous envi-ronmental pollutant. Cell damaging pro p e r-ties of phenol were first exploited in anti-spasticity treatment with intrathecal admin-i s t r a t i o n .6 2 , 6 3 Khalili and collaborators64 t h e np e rf o rmed perineural injections andH a l p e rn and Meelhuysen,6 5 D e l a t e u r,9 3 a n dAw a d4 p i o n e e red intramuscular injections.Since then, phenol has been used to contro lmuscle overactivity in the upper or lowerlimbs, mainly in adult stroke or brain trau-ma patients.5 1 , 9 5 , 9 6 H o w e v e r, Spira, and morerecently Ya d a v, re p o rted the successful useof phenol in children with cerebral palsy.9 7 , 7 1
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Metabolism and risksFollowing oral or intravenous administra-tion in mice, phenol metabolites are phenolsulfate, phenol glucuronide, and hydro-quinone glucuronide, with more oxidationof phenol to hydroquinone in males than inf e m a l e s .9 8 Both phenol and hydro q u i n o n ehave synergistic effects in myelotoxicity andgenotoxicity in the bone marrow of mice.9 9
To our knowledge, no re t rospective orp rospective studies have been made inpatients about the genotoxic and myelotoxicrisk of phenol injections.
Histological eff e c t sPerineural injections: Like alcohol, phenold e n a t u res protein, causing tissue necro s i s .H o w e v e r, some authors suggest that,depending on the concentration of phenolused, the extent of protein denaturation andthe subsequent local injury are more com-plete than those due to alcohol.5 1 As withlocal anesthetics and alcohol, the destru c t i v ee ffects of phenol have been also confirm e das nonselective across fiber sizes.6 8 They cor-relate with the concentration of phenola p p l i e d .6 8 At 5% in saline, coagulation ofperipheral nerves at the site of injectionoccurs 1 hour following injection, with theaxons in the center of the nerve being not orless affected when phenol is dripped ontothe nerve. Wallerian degeneration occurs inthe weeks following injection and eventual-l y, there is re g rowth of most axons.1 0 0
H o w e v e r, after administration of only 2%aqueous phenol, damage to the micro - c i rc u-lation occurs around the nerve, includingslugging, oscillation, plasma skimming, andi n v e rted flow.1 0 1 This may lead to occlusionof small blood vessels and fibrosis in theinjected area, and might account for long-t e rm eff e c t s .1 0 0 , 1 0 1 , 1 0 2
The tissue-destructive effect of phenol ispotent: A case of focal necrosis of the ure t e rwas re p o rted following CT-guided phenols y m p a t h e c t o m y,103 and phenol is commonlyused in experimental cardiology to produce
localized heart infarc t i o n .1 0 4 H o w e v e r,Koman re p o rts that neutralization with alco-hol limits damage to surrounding soft tissuewhen phenol is appled directly to anexposed peripheral nerv e .51 This forms thebasis of the “open” techniques that havebecome more frequent in recent years.7 1 , 9 5 , 9 6
Intramuscular injections: Intramuscular injec-tions of aquenous phenol in rats and dogsp roduces neurogenic atrophy of the muscleby 2 months as well as collateral re i n n e rv a-tion and regeneration of muscle fibers.H a l p e rn105 also found local necrosis of themuscle and an associated inflammatoryreaction of the fascia and subfascial tissues.The reaction began within days of the pro-c e d u re in dogs and rats, was intensified bythe end of 2 weeks, and then began toresolve. Return to normal of the muscle at 3months only occurred if the concentrationof phenol used was lower than 3%.1 0 5
Other sites of injections: Other injection sitesfor alcohol appear to be dangerous. Sincethe initial works of Nathan, and Kelly eta l . ,6 2 , 6 3 subarachnoid administration of phe-nol has been abandoned in antispastic indi-cations because of the spinal risks associatedwith this technique. It continues to be usedin analgesic indications for intractable can-cer pain.1 0 6 , 1 0 7 Epidural phenol injectionshave been used to target otherwise inacces-sible proximal muscles (iliopsoas, quadratusl u m b o rum) or lumbar or sacral paraspinalmuscles. However, histopathologic changesin primate spinal cord after epidural 3% and6% phenol administration have re c e n t l ybeen systematically studied.1 0 8 With bothdilutions, damage affected pre d o m i n a n t l yposterior nerve roots, and there was alsod i rect cord injury. In addition, the authorspointed out the greater difficulty contro l l i n gthe spread of epidural vs. subarachnoidphenol, and they concluded that the risks ofepidural phenol may outweigh the benefits
F i n a l l y, the intrinsic complications of anyepidural intervention must be considere d ,especially the possibility of spinal subduralh e m a t o m a .109 Lumbosacral paravert e b r a lblocks with phenol carry the risk of acci-dental intrathecal injection by way of theroot sleeves,110 and this could also causecauda equina or spinal cord injury (seebelow).
Physiological eff e c t sConcentrations lower than 3%: With perineur-al injections of concentrations up to 2% inw a t e r, phenol has only local anestheticp ro p e rties. It may be faster acting than 2%l i d o c a i n e1 1 1 and has been used as a topicallocal anesthetic agent.1 1 2 This fast eff e c tp robably accounts for the transient anesthe-sia and weakness that are commonly seenafter nerve blocks and can be a confoundinge ffect if the assessment is made too earlyafter the injection. Studies of the actionpotentials obtained by electrical stimulationafter injection of 2% phenol around a nerv eshow a depression with a biphasic timec o u r s e .1 0 1 A first depression occurs soonafter injection, followed by a transientre c o v e ry, and then a second depre s s i o nappears after 30 minutes. The first depre s-sion corresponds to the local anestheticp ro p e rt y, while the second depression isc o n s i d e red to be due to circ u l a t o ry damageof the nerve fibers1 0 1 (see above). At verylow concentration (0.5%) the local anesthet-ic effect of phenol is synergistic with that ofa local anesthetic of long duration of eff e c t( b u p i v a c a i n e ) ,1 1 6 in contrast with the pro p o-fol/prilocaine combination discusseda b o v e .5 6 C l i n i c a l l y, concentrations lowerthan 3% generally give poor results andre q u i re frequent repetition of blocks.1 1 4
Hence, the dilution used most usually inclinical indications is 3% to 6%.
Concentrations above 3%: At concentrationsabove 3%, there is an almost immediate andthen monophasic, constant denervation inEMG studies in humans.111,112,113 This 3%limit is consistent with the pattern of histo-logical results presented above.1 0 5 A re c e n tstudy examined the physiological effect of a5% aqueous solution of phenol whenapplied to a rat nerv e .1 1 5 Axonal degenera-tion was evident within the injected nerve 2days following phenol application. By 2weeks, the innervated muscles had atro-phied to almost 50% of contro l .R e i n n e rvation occurred between 2 and 4weeks following the nerve block, but at 5months, maximal tension of the innerv a t e dmuscle was only 74% of control and themuscle consisted of more fast fibers on aver-age. The authors concluded that the injuryto the nerve caused by 5% phenol wasc h ronic and more severe than a crush injury.
D i ff e rential effect on descending and reflex con-traction? With phenol treatment, as withlocal anesthetics and alcohol blocks, itappears that strength is more often pre-s e rved than stretch re f l e x e s .6 9 , 7 0 , 8 4 F i s h e r7 6 , 1 1 7
has noted that the relative pre s e rvation ofv o l u n t a ry strength in the face of markedreduction in spasticity does not have to bethe result of a putative immunity of motorn e u rons to neurolytic agents (a hypothesiswhich was ruled out histologically,6 8 s e eabove). Interrupting both eff e rents (alphaand gamma motor neurons) and aff e re n t s( f rom the muscle spindle) may be enough tohave a synergistic effect upon reflex contrac-tions, greater than the effect on contractionsof descending origin which bypass the seg-mental aff e rent pathway. This may be tru eeven when only interrupting the alpha andgamma eff e rents, since gamma eff e rents actfunctionally as aff e rents, in that theyenhance the messages coming from spin-dles. Hence partial curarization, whicha ffects only the neuromuscular junction andnot aff e rents, has also been shown to re d u c espasticity to a greater degree than voluntarys t re n g t h ,1 1 8 and the same phenomenon was
K E Y P O I N T S
• Subarachnoid and
epidural
administration of
phenol carry
important risks of
spinal lesion.
Caution is also
warranted with
paravertebral
blocks
• Stretch reflexes
are more reduced
than strength after
local anesthetics,
alcohol, and
phenol injection
Local treatments Muscle & Nerve Supplement 6 1997S18
recently observed with injections of botu-linum toxin in the upper limb of hemiplegicp a t i e n t s .54
The diff e rential effect on voluntary andreflex contractions may there f o re dependl a rgely on the number of paralyzed periph-eral neurons, with reflex functions such asspasticity being affected by a relative smallreduction in number, and voluntarys t rength or other forms of “non-aff e re n t ”command of movements (includingunwanted co-contractions in spasticpatients) requiring a quantitatively larg e rreduction. In any case, the existence of thisd i ff e rential effect may not be of clinical re l e-vance, since only a mild weakening aftern e rve block may be insufficient to give afunctional benefit from the injection undermost circ u m s t a n c e s .5 2 , 5 4
When correlating histological and physio-logical effects, it appears that significante ffect depends on the use of a concentrationhigher than 3%, with histological destru c-tion of nerve, as with alcohol. Many sidee ffects observed with phenol injections arethe direct consequence of the re q u i red his-tological damage.
Adverse eff e c t sA p a rt from the pain during injection, theother tolerance issues are long-term side-e ffects and have been an important pro b l e mwith phenol injections.
Pain during injection: The patient usuallyfeels a burning sensation during the injec-t i o n .5 2 To our knowledge, this has not beenc o m p a red in a controlled fashion to the painexperienced during alcohol injections.
C h ronic dysesthesia and pain: The incidenceof dysesthesia re p o rted after peripheralblocks with phenol has varied from 2% to3 2 % .5 2 , 1 1 9 , 1 2 0 The risk seems higher with sen-sorimotor blocks than with motor blocks5 2
but the number of patients treated wassmaller with the latter technique.Dysesthesias are usually re p o rted from a fewdays to about 2 weeks after the pro c e d u reand are generally experienced as a burn i n gp a resthesia exacerbated by light tactile stim-ulation, often only in a small portion of thes e n s o ry distribution of the nerve that wasb l o c k e d .119 The typical duration is severalw e e k s5 2 , 1 1 9 but chronic dysesthesia has beenre p o rt e d .1 2 0 The etiology is not clear, thoughit may be associated with abnorm a lre g rowth of sensory axons.
A uniformly applied compressive garm e n tsuch as sock, glove, elastic wrap, or lycras l e e v e1 8 , 2 3 may minimize the effects of others u p e rficial stimulation and decrease edemaif present. Some authors have attempted toreblock the nerve with phenol.1 1 9 Braun andcolleagues employed surgical neurolysis toresolve persistent dysesthesia caused bymedian nerve blocks in 2 patients.1 2 1
Sometimes systemic treatment is re q u i re d .9 3
T h e re have been only a few publishedre p o rts of severe, lancinating pain after phe-nol sensorimotor blocks, including one inthe fore a rm following median nerve blockwith phenol at the level of the elbow.1 2 0
H o w e v e r, the frequency of this side eff e c tmay be underestimated since most cases arep robably not re p o rted. The same is also tru efor alcohol blocks.87
Vascular complications: Peripheral edema,p a rticularly in the lower extre m i t y, may fol-low chemical neurolysis and is said to usual-ly resolve within a week or two.5 2 A c c i d e n t a lintravascular injection has not been re p o rt e din association with phenol neurolysis, butinjections of phenol into the stellate gan-glion and into the cervical subarachnoidspace for analgesic indications have beenassociated with infarction in the cerv i c a lspinal cord and cere b e l l u m .106 Deep venoust h rombosis has also been re p o rted after phe-nol neuro l y s i s .122 Vascular risks includen e c rosis of the intima of arteries and veinsand thrombotic occlusion of small vessels.This makes the routine precaution of aspi-rating before injecting even more import a n twith this compound. Other mechanismsthat could contribute to deep venous thro m-bosis in an injected limb include trauma tothe vein or loss of muscle pumping action,leaving the extremity more susceptible tostagnation of venous blood. However, thesemechanisms exist with injection of anyblocking agent.
Cutaneous side-eff e c t s : Skin slough has beenre p o rted after phenol injections.5 1
Excessive motor weakness: As with alcoholblocks, most patients have pre s e rvation ofs t re n g t h .64,119 Aggravation of disability byexcessive paralyzing effects is a potentialrisk with both perineural and intramuscularblocks. As discussed above, the use of diag-nostic blocks with local anesthetic agentsmay help anticipate functional consequencesof a more permanent pro c e d u re. However, alocal anesthetic block may not be equivalentto a block with phenol, especially since itmay underestimate the consequences ofexcess weakness.
S e n s o ry loss: P e rmanent functional loss ofsensation is a rare occurrence followingmixed sensorimotor nerve blocks with phe-n o l .5 2 S e n s o ry loss is common in the firsthours or days following the pro c e d u re butthis usually re s o l v e s .1 1 9 , 5 2
Wound infection: Phenol is bacteriocidal atthe concentrations used for neurolysis (as isalcohol), and local infection at the site ofinjection has been rarely re p o rt e d .5 1 , 1 2 3
Systemic side effects: O v e rdose with phenolcauses tre m o r,1 2 convulsions, central ner-vous system depression, and card i o v a s c u l a rc o l l a p s e .5 2 The amount of phenol ro u t i n e l yused for nerve blocks however, is usuallywell below the lethal range, which starts at8.5 g.1 1 2 A 10 mL injection of 5% phenolcontains only 0.5 g of phenol. To re m a i nwithin safe limits, no more than 1 g shouldbe injected in one day.5 2 O v e rdosage has notbeen re p o rted in association with phenoln e u rolysis. However, the possibility of sys-temic side effects warrants caution in avoid-ing accidental intravascular injection. Thepotential of myelotoxic and genotoxic com-plications has been addressed above.
P a rticular tolerance issues with intramusculari n j e c t i o n s : The additional side effects associ-ated with motor nerve blocks are local painand swelling that may be present for a fewdays or occasionally longer.6 5 , 1 2 5 This localreaction can mimic deep venous thro m b o-sis, especially when it occurs in the calf.Induration with tender nodules may appear1 to 3 weeks after the injection.1 2 6 A re c e n tinvestigation of 9,845 children re c e i v i n grepeated intramuscular injections of peni-cillin diluted by only 1.5% to 2% phenolre p o rted 122 cases of “gluteal muscle con-t r a c t u re,” which corresponds to a morbidityof 1.36% for this side eff e c t .1 2 7
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Intensity and Duration of Eff e c tIntensity of effect: The literature on the eff i c a-cy of phenol consists only of anecdotalre p o rts. It is interesting, however, to com-p a re re p o rts of authors who used diff e re n tconcentrations. Khalili1 2 8 used 3% phenolfor tibial nerve blocks in a patient with dys-tonia who developed superimposed spasticright hemiplegia following a neuro s u rg i c a lp ro c e d u re. While this resulted in re d u c e dankle clonus, dystonic and voluntary con-traction of the plantar flexors were nota ffected. Halpern and Meelhuysen, however,re p o rted good efficacy from higher concen-tration injections on “extrapyramidal” rigidi-ty of sternomastoid and leg adductors in 2patients with Parkinson’s disease.6 5 A possi-ble explanation is the higher concentrationsused by the Danish authors (3% to 5% usedin paravertebral blocks1 2 9) than those usedby Khalili (only 2% to 3% phenol6 4 , 1 2 8) ,which may be high enough to block thedescending output to the muscle rather thanjust the reflexes from aff e rents within them u s c l e .
Modifications of aff e rent input to the spinalc o rd by the block may account for someclinical effects, whether these aff e rent modi-fications are due to direct aff e rent block bythe compound or simply to a massivereduction of aff e rent impulses from a musclethat now does not contract as much. Forexample, Mooney and colleagues1 0 2 f o u n dthat 2 of 8 patients with upper extre m i t ys y n e rgy patterns had global weakening ofthese patterns following phenol neuro l y s i sof only motor branches of the mediann e rve. These observations appear consistentwith the fact that co-contractions are facili-tated by the stretch of co-contracting musclein spastic patients.9
Duration of effect: The re p o rted duration ofclinical effect of phenol injections has beenvariable, in contrast to some precise physio-logical data obtained re c e n t l y.1 1 5 The re c u r-rence of overactivity in injected muscles isbelieved to be due to subsequent re g e n e r a-tion of injured motor nerves taking placeafter the Wallerian degeneration.51,115 As dis-cussed above, long-term effects may be sec-o n d a ry to muscle necrosis and fibro s i s ,endoneural fibrosis, or local vascular injurycaused by nonspecific protein denaturingwithin the injection zone.51 K h a l i l i1 2 8 re p o rt-ed a duration of efficacy from 10 to 850days in a series of 94 peripheral nerv eblocks using 2% to 3% phenol (average 317days = 10 to 11 months). Petrillo and col-l e a g u e s1 1 9 re p o rted a slightly longer durationof effect of tibial nerve blocks with 5% phe-nol (9 to 22 months with an average of 13months). Katz and colleagues1 3 0 found thatof 31 effective peripheral nerve blocks outof a total of 56 using 3% phenol, only 9lasted for longer than 1 month. After intra-muscular neurolysis with 5% phenol, Eastonet al.126 re p o rted similar variability in theduration of effect, ranging from 1 to 36months. These are some examples of anabundant and divergent literature .52 T h e rea re no controlled comparisons of the eff e c tof the treatment site on outcome.
Overall, several factors may influence theduration of effect, but none has been stud-ied in a controlled fashion:- Concentration and volume used for injec-t i o n1 0 2
- Site of the block: intramuscular, peripheraln e rve, paravertebral, “intramuscular targ e t-ing endplates”9 3
- Treatment variables after the block; forexample, if the muscle is eff e c t i v e l ys t retched after nerve block, spasticity maybe further controlled and a longer term ben-efit could ensue1 5 , 1 6 , 1 7
- The presence of selective motor control inthe muscles supplied by the nerve tre a t e dprior to the block may be associated with alonger duration of eff e c t1 2 1
- The specificity and sensitivity of themethod used to evaluate the degree of spas-t i c i t y4 , 5
- Repeat injections: Aw a d9 4 and others havere p o rted that the effect of phenol injectionsmay become definitive after 3 or 4 injec-tions. Others do not re p o rt a diff e rent dura-tion of effect from first injections.1 2 0
Technical IssuesSelected peripheral nerves can be injectedwith 4% to 6% aqueous phenol perc u t a-neously or at higher concentrations underd i rect vision.71 Glycerin may be added torender the phenol more soluble in aqueouss o l u t i o n s .5 1 Quantities of 5% aqueous phe-nol injected onto peripheral nerves usuallyv a ry from 1 to 10 mL.1 1 9 Adjustment of thea p p ropriate position of the needle tipshould be done using the same technique ofe x p l o r a t o ry stimulation as described abovefor local anesthetics. In children with cere-bral palsy, Koman advises general anesthesiafor perineural injections in order to exposethe target peripheral nerve surg i c a l l y, and atleast deep conscious sedation for perc u t a-neous injections in a safe manner.9 1 G e n e r a lanesthesia is also recommended by othersfor intramuscular injections in children withc e rebral palsy.1 3 1
Sites of BlocksPerineural: In comparison with motor block,perineural block carries the additional riskof chronic dysesthesia, but may have alonger duration of effect. One must exerc i s ecaution in the use of a perineural pro c e d u rein a patient for whom a mild pain pro b l e mmight become the source of significant dis-ability (i.e., secondary gain) or the focalpoint for the displacement of other anxi-e t i e s .52
Perineural in lumbosacral paravert e b r a lre g i o n s : Taking the risk of chronic dysesthe-sia may be the only solution for musclesthat are difficult to access dire c t l y, such asthe psoas major because of its size, thequadratus lumborum because of its pro x i m-ity to the peritoneal cavity and the kidney,and the paraspinal lumbar or sacralm u s c l e s .66 To relax these muscles, injectioncan be made at the paravertebral level,1 2 8 , 1 2 9
because the peritoneal cavity is well pro t e c t-ed by the combined depth of the paraspinaland psoas muscles.5 2 Either mixed sensori-motor or motor nerves can be isolated inthis are a .5 2 H o w e v e r, this site of injectionalso carries the risk of accidental intrathecalpenetration of phenol110 as discussed above.In addition, a muscle such as iliopsoas istechnically difficult to identify and fluoro -ro s c o p y, ultrasound, or CT guidance may bere q u i re d .
Intramuscular injections - endplate targ e t i n gtechnique: An intramuscular block, byd e s t roying distal nerve branches, may alloweasier titration of the weakening effect thana more proximal block of the whole tru n k ,although the intramuscular pro c e d u re maybe more painful.1 3 1 The identification ofsmall motor branches can be facilitated bythe use of charts that depict the usual loca-tion of motor points within a given mus-
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c l e .1 3 2 To optimize the eff i c a c y, DeLateur9 3
p roposed to inject as close as possible toendplate areas. It has been shown thatmotor endplates do not occur at random inmost animal or human muscles.1 3 3 I n s t e a d ,they cluster at characteristic areas withinmost muscles (the “innervation band”),since the endplate generally lies near themidpoint of any given muscle fiber.1 3 4
H o w e v e r, there are exceptions to this ru l e ;for example, there are numerous innerv a t i o nbands scattered throughout sartorius andgracilis muscles.134,135
Since there is no noninvasive way to deter-mine where the endplate-rich areas are in amuscle, DeLateur used a hollow Te f l o n®-coated injection needle as an electro m y o-graphic exploring electrode to find charac-teristic electrical potentials in the muscle atrest, signifying the immediate proximity ofe n d p l a t e s .9 5 These include the characteristic“endplate ripple” or endplate noise,136,137, 138
a low-voltage increase in irregularity of thebaseline of about 10-40 µV;1 3 6 a n dmonophasic spike discharges, or diphasicwith negative onset, entirely or almoste n t i rely negative in sign, with a random pat-t e rn of discharge (as opposed to fibrillationpotentials). Buchtal and Rosenthal showedthat when the concentric needle was dis-placed slightly from the area of endplate rip-ple, the discrete monophasic negative spikesw e re re a c h e d .1 3 6 A c c o rd i n g l y, when themonophasic negative spikes are found, theexploring electrode is close to the endplatez o n e .9 3 Because the contact of the needlewith endplate zones can be painful for thepatient, movements of the exploring elec-t rode must be slow and smooth. Finally,xylocaine can be used for skin wheals overeach of the approximate cutaneous sites cor-responding to endplate areas. Several are a scan be explored through a single skin whealover the pre d e t e rmined cutaneous area. Inaddition, it is possible that the deaff e re n t a-tion of the skin also helps reduce clonic fir-
ing of the motor units.9 3 While DeLateur’stechnique is attractive, it has not been re p l i-cated by others and its practicality re m a i n sto be confirmed.
Open nerve blocks: These can be perf o rm e dto ensure that only motor branches arebeing blocked, but this involves anesthesiaand an incision that might temporarilyrestrict the use of the extre m i t y.3 2 Sedation isre q u i red if the adult patient is likely to haved i fficulty tolerating the pro c e d u re. In youngc h i l d ren or aggressive, brain-injure dpatients, general anesthesia may be the onlyway to ensure a proper completion of theb l o c k .120,126,131 Anatomic guides may help thepractitioner in muscle and nerve localiza-t i o n .1 1 0 , 1 3 9 , 1 4 0
Topical phenol and alcohol in other indicationsA p a rt from intramuscular use of phenol inspasmodic tort i c o l l i s ,141 exploitation of thetissue destructive effects of phenol and alco-hol have included sclerotherapy in hemor-ro i d s1 4 2 or esophageal varices,1 4 3 c h e m o n u-cleolysis in intradiscal injections as an alter-native to surgical treatment for lumbar disch e rn i a t i o n ,1 4 4 pain relief by re t robulbar injec-tion in cases of blind painful eye,1 4 5 s u b t r i g-onal injection in hyperactive bladder,146 l i m bischemia by sympathectomy,1 4 7 p ro x i m a lgastric vagotomy in re f r a c t o ry ulcers,1 4 8 a n dh y p e rh i d rosis with caudal epidural injectionin patients with cervical cord injury.1 4 9
C o n c l u s i o n s
Patients with damage to central motor path-ways causing disabling focal muscle overac-tivity may benefit from chemical neuro l y s i sby injection of alcohol or phenol into theoveractive muscles or their supplyingn e rves. Whichever blocking agent is underconsideration, one may question whetherfunctional benefit from the block dependson significant weakening in the targ e t e dmuscle. Local anesthetic blocks may be usedto help predict whether long duration
blocks are warranted, with the same caveat:Without a significant weakening effect, atest with local anesthetic may not bring use-ful information on the potential fori m p rovement or the mechanisms re s p o n s i-ble for a focal motor impairm e n t .
In the last three decades, alcohol and phe-nol blocks have too rarely been perf o rm e dby the same groups and in the same indica-tions. For each compound, there is a needfor placebo-controlled studies to reach firmconclusions on their safety and eff i c a c y. Theexperience with alcohol mainly concern sintramuscular injections in children, whilephenol has chiefly been used with perineur-al injections in adults. The number of sidee ffects re p o rted with phenol is larger thanwith alcohol, as is the total number of pub-lications re p o rting phenol use. Whether thebenzyl core of phenol carries an additionalmyelotoxic or genotoxic risk, especially inc h i l d ren, remains to be evaluated.Physicians who regularly administer blocksemphasize that safety increases with theexperience of the clinician and that nerv eblocks should not in general be perf o rm e dby physicians who use them only occasion-a l l y, since proper perf o rmance of the tech-nique re q u i res training and experience.
Comparison with Botulinum To x i nIn comparison with botulinum toxin, alco-hol and phenol have advantages in theirearly onset of action and perhaps longerduration of effect, low cost, lack of anti-g e n i c i t y, better stability, and a greater flexi-bility in the timing of injections. However,their lack of selectivity on motor function,t i s s u e - d e s t ructive effect, propensity to causepain during injection, and adverse eff e c t ssuch as chronic painful dysesthesia, localmuscle transformations, or vascular re a c-tions may favor the use of botulinum toxin.
In current practice, many clinicians use bothtypes of treatment in combination. Alcoholand phenol are usually injected perineurallyto block large muscles, for which the eff e c-tive botulinum toxin dose would appro a c hor exceed the ceiling dose. Botulinum toxinis usually re s e rved for injection into smallerand more distal muscles that can be targ e t e ds e l e c t i v e l y.
In the future, indications for neuro l y t i cagents and for botulinum toxin may alsohave to be based on the severity and pro g-nosis of the patient, and the goals of tre a t-ment. The absence of histological destru c-tion after repeated botulinum toxin injectionand the specific action on eff e rent fibersmay make this the preferable agent wheret h e re is hope of re c o v e ry of active functionof the injected limb. Because of their chro n-ic histological effects and the destruction ofs e n s o ry fibers, alcohol or phenol may pro v em o re appropriate than botulinum toxin incases where treating muscle overactivity isp e rf o rmed primarily for hygiene and com-f o rt, i.e., in patients with severe deficitsw h e re re c o v e ry of intact muscle and sensoryp e rception is not expected. In an economiccontext where cost effectiveness of therapyis critical, controlled comparative studiesbetween neurolytic agents and botulinumtoxin are needed in specific patient popula-tions to determine the appropriate indica-tions for each.
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