S P A S T I C I T Y D.S.N.V. - UniGE Motor disorder characterized by velocity dependent increase in tonic stretch reflexes and exaggerated tendon jerksMotor

S P A S T I C I T YS P A S T I C I T Y

D.S.N.V. - UniGED.S.N.V. - UniGED.S.N.V. - UniGED.S.N.V. - UniGE

• Motor disorder Motor disorder characterized by characterized by velocity dependent velocity dependent increase in tonic increase in tonic stretch reflexes and stretch reflexes and exaggerated tendon exaggerated tendon jerksjerks

UPPER MOTONEURONE UPPER MOTONEURONE SYNDROMESYNDROME

• Negative phenomenaNegative phenomena

- - WeaknessWeakness

- Fatigability- Fatigability

- Reduced MUs - Reduced MUs

recruitmentrecruitment

- Reduced dexterity- Reduced dexterity


• Positive phenomenaPositive phenomena

- Tone increase - Tone increase

- Stretch hyperreflexia- Stretch hyperreflexia

- Clonus - Clonus

- Flexor-extensor spasms- Flexor-extensor spasms

- Abnormal cutaneous r.- Abnormal cutaneous r.

- Babinski sign- Babinski sign

- Cocontraction/Dystonia- Cocontraction/Dystonia

Higher Higher CentresCentres

Spinal Cord Spinal Cord CircuitryCircuitry

Skeletal Skeletal MuscleMuscle

PeripheralPeripheralAfferentsAfferents

++

--

++ -- PathwaysPathwaysDescendingDescending


SPASTICITY and UMN SyndromeSPASTICITY and UMN SyndromePathophysiological MechanismsPathophysiological Mechanisms

• Defective InhibitionDefective Inhibition MNs MNs

Postsynaptic Postsynaptic MNs inhibition MNs inhibition

Presynaptic Ia inhibitionPresynaptic Ia inhibition

Excitatory group II INsExcitatory group II INs

• Defective ExcitationDefective ExcitationInhibitory Ia-INs ‘ Reciprocal’Inhibitory Ia-INs ‘ Reciprocal’

Inhibitory Ib- INs ‘Autogenetic’Inhibitory Ib- INs ‘Autogenetic’

Renshaw cells ‘Recurrent’Renshaw cells ‘Recurrent’


SPASTICITY SPASTICITY Ia Pre-synaptic InhibitionIa Pre-synaptic Inhibition


SPASTICITY SPASTICITY Ia Reciprocal InhibitionIa Reciprocal Inhibition


SPASTICITY SPASTICITY Interneuronal ExcitabilityInterneuronal Excitability


SPASTICITY and UMN SyndromeSPASTICITY and UMN SyndromePathophysiological MechanismsPathophysiological Mechanisms

• Motor Units changesMotor Units changes – collateral sproutingcollateral sprouting

– transynaptic degenerationtransynaptic degeneration

– dendrite shortening dendrite shortening

– silent synapses activationsilent synapses activation

– denervation supersensitivitydenervation supersensitivity

• Changes of Stiffnes and Changes of Stiffnes and

muscle propertiesmuscle properties


Muscle & Nerve suppl 6 - 1997Muscle & Nerve suppl 6 - 1997


TREATMENT of SPASTICITYTREATMENT of SPASTICITYTherapeutic ObjectivesTherapeutic Objectives

• TECHNICAL:TECHNICAL:- Promote: TONE REDUCTION- Promote: TONE REDUCTION

- Improve: RANGE of MOTION, JOINT POSITION- Improve: RANGE of MOTION, JOINT POSITION

- Facilitate: REHABILITATION- Facilitate: REHABILITATION

• FUNCTIONAL:FUNCTIONAL:- - Improve: GAIT, HYGIENE, ADL, EASE of CAREImprove: GAIT, HYGIENE, ADL, EASE of CARE

- Reduce: SPASMS, PAIN- Reduce: SPASMS, PAIN

D.S.N.V.- UniGED.S.N.V.- UniGED.S.N.V.- UniGED.S.N.V.- UniGE

PHARMACOLOGIC TREATMENT PHARMACOLOGIC TREATMENT OF SPASTICITYOF SPASTICITY

• Recommended when spasticity produces a clinical disability Recommended when spasticity produces a clinical disability by interfering with posture, motor capacity, nursing, ADLby interfering with posture, motor capacity, nursing, ADL

• Indicated when muscle overactivity is diffusely distributed Indicated when muscle overactivity is diffusely distributed (spinal > cerebral)(spinal > cerebral)

• Timed in the early stages to prevent permanent Timed in the early stages to prevent permanent musculoskeletal deformities or contracturesmusculoskeletal deformities or contractures

• The goal is to decrease spinal reflex excitability by:The goal is to decrease spinal reflex excitability by:

- reducing the release of excitatory neurotransmitters - reducing the release of excitatory neurotransmitters

- potentiating the activity of inhibitory circuits- potentiating the activity of inhibitory circuits

D.S.N.V.- UniGED.S.N.V.- UniGED.S.N.V.- UniGED.S.N.V.- UniGE

NEUROTRANSMITTERS ANDNEUROTRANSMITTERS ANDPHYSIOLOGICAL MECHANISMS PHYSIOLOGICAL MECHANISMS

INVOLVED IN SPASTICITYINVOLVED IN SPASTICITY

GABAGABA

Glycine Glycine

GlutamateGlutamate

EAAsEAAs

NoradrenalineNoradrenaline

SerotonineSerotonine


DIAZEPAMDIAZEPAM

• Aumenta l’affinità del Aumenta l’affinità del GABA per il suo GABA per il suo recettore ionoforico recettore ionoforico (GABA a)(GABA a)

- Livello postsinaptico: aumento Livello postsinaptico: aumento conduttanza Cl, conduttanza Cl, iperpolarizzazione, inibizione iperpolarizzazione, inibizione postsinapticapostsinaptica

- Livello presinaptico: aumento Livello presinaptico: aumento conduttanza Cl, conduttanza Cl, depolarizzazione, inibizione depolarizzazione, inibizione rilascio aminoacidi eccitatoririlascio aminoacidi eccitatori


BACLOFENBACLOFEN

• Stimolazione recettori Stimolazione recettori GABA b (metabotropici)GABA b (metabotropici)

- - Livello postsinaptico: aumento Livello postsinaptico: aumento conduttanza K, conduttanza K, iperpolarizzazione cellulare, iperpolarizzazione cellulare, inibizioneinibizione

- Livello presinaptico: blocco dei - Livello presinaptico: blocco dei canali del Ca, alterazione canali del Ca, alterazione liberazione aminoacidi eccitatoriliberazione aminoacidi eccitatori



DIAZEPAM (2)DIAZEPAM (2)

• CLINICAL EFFECTS:CLINICAL EFFECTS:- Reduction of resistance to stretch (increased range of motion)eduction of resistance to stretch (increased range of motion)

- Reduction of deep tendon reflexes and of painful spasms- Reduction of deep tendon reflexes and of painful spasms

• SIDE EFFECTS:SIDE EFFECTS:- Sedation & drowsiness, Attention & memory impairment- Sedation & drowsiness, Attention & memory impairment

- Weakness amd motor incoordination- Weakness amd motor incoordination

- Tolerance, dependency (withdrawal phenoemena)- Tolerance, dependency (withdrawal phenoemena)

• INDICATIONS:INDICATIONS: SCI - MS (possible: TBI - CP - CVA) SCI - MS (possible: TBI - CP - CVA)

• EFFICACY SHOWN BY DOUBLE-BLIND PROTOCOLS IN SC EFFICACY SHOWN BY DOUBLE-BLIND PROTOCOLS IN SC LESIONS (POSSIBLE STRENGTH-GAIT DETERIORATION) LESIONS (POSSIBLE STRENGTH-GAIT DETERIORATION)



BACLOFEN (2)BACLOFEN (2)

• CLINICAL EFFECTS:CLINICAL EFFECTS:

- Reduction of flexor-extensor spasmsReduction of flexor-extensor spasms

- Reduction of mono- polysynaptic reflexes- Reduction of mono- polysynaptic reflexes

- Reduction of sphincter hyperreflexia- Reduction of sphincter hyperreflexia

• SIDE EFFECTS:SIDE EFFECTS:

- Sedation, Drowsiness, Fatigue, Confusion, Dizziness

- Hypotonia, Ataxia

• INDICATIONS:INDICATIONS: Spinal s Spinal spasticity pasticity

• EFFICACY SUFFICIENTLY DOCUMENTED IN PATIENTS EFFICACY SUFFICIENTLY DOCUMENTED IN PATIENTS WITH SC LESIONS (LESS IN CEREBRAL)WITH SC LESIONS (LESS IN CEREBRAL)

INTRATHECAL BACLOFENINTRATHECAL BACLOFEN

• Consists of direct long-term delivery of baclofen to the Consists of direct long-term delivery of baclofen to the intrathecal space via an implanted programmable pumpintrathecal space via an implanted programmable pump

• Indicated in patients with severe spasticity, not managed by Indicated in patients with severe spasticity, not managed by oral baclofen (inadequate BBB penetration, side effects) or oral baclofen (inadequate BBB penetration, side effects) or other oral medicationsother oral medications

• Same clinical effects at much lower doses (1 %)Same clinical effects at much lower doses (1 %)

• - Selection- Selection

- Screening- Screening

- Implantation- Implantation

- Dose adjustment & maintenance- Dose adjustment & maintenance


INTRATHECAL BACLOFEN (2)INTRATHECAL BACLOFEN (2)

• Benefits have been documented by placebo-controlled Benefits have been documented by placebo-controlled studies in severely disabled nonambulatory patients with studies in severely disabled nonambulatory patients with overactivity mainly in ther lower limbs and with flexor overactivity mainly in ther lower limbs and with flexor spasmsspasms

• Reduction of spasticity, spasms and painReduction of spasticity, spasms and pain

Sleep improvement and better bladder managementSleep improvement and better bladder management

• IMPROVEMENT IN QUALITY OF LIFEIMPROVEMENT IN QUALITY OF LIFE

• COMPLICATIONS: COMPLICATIONS: infection, pump dysfunction, high cost infection, pump dysfunction, high cost and invasivenessand invasiveness


TIZANIDINATIZANIDINA

• Attività Attività 2-agonista 2-agonista (spinale e sopra-spinale)(spinale e sopra-spinale)

- - riduce la liberazione di riduce la liberazione di aminoacidi eccitatori nel aminoacidi eccitatori nel midollo spinale midollo spinale

- inibisce la via coerulo-spinale - inibisce la via coerulo-spinale (questa via normalmente (questa via normalmente facilita i circuiti spinali)facilita i circuiti spinali)


TIZANIDINE (2)TIZANIDINE (2)

• CLINICAL EFFECTS: CLINICAL EFFECTS:

- - reduction of tonic stretch polysynaptic reflexes reduction of tonic stretch polysynaptic reflexes

- reduction of cocontraction- reduction of cocontraction

• SIDE EFFECTS: SIDE EFFECTS: sedation, dizziness, dry mouth, sedation, dizziness, dry mouth, but not weaknessbut not weakness

• INDICATIONS:INDICATIONS: MS - SCI (possible: cerebral spasticity) MS - SCI (possible: cerebral spasticity)

• EFFICACY PROVEN BY PLACEBO-CONTROLLED EFFICACY PROVEN BY PLACEBO-CONTROLLED STUDIES (> DIAZEPAM IN CEREBRAL). NO DEFINITE STUDIES (> DIAZEPAM IN CEREBRAL). NO DEFINITE FUNCTIONAL CHANGESFUNCTIONAL CHANGES


DANTROLENEDANTROLENE

• Peripheral inhibition of calcium release from sarcoplasmic Peripheral inhibition of calcium release from sarcoplasmic reticulum. Decreased excitation-coupling reaction.reticulum. Decreased excitation-coupling reaction.

• CLINICAL EFFECTS:CLINICAL EFFECTS:

Reduction of muscle tone, phasic reflexes and spasms Reduction of muscle tone, phasic reflexes and spasms

Increased range of passive motionIncreased range of passive motion

• INDICATIONS:INDICATIONS: CVA - CP (possible: TBI - SCI -MS) CVA - CP (possible: TBI - SCI -MS)

• SIDE EFFECTS: SIDE EFFECTS:

hepatotoxicity, GE symptoms, weakness, hepatotoxicity, GE symptoms, weakness, but less sedationbut less sedation


ANTISPASTIC DRUGSANTISPASTIC DRUGS

• Clonazepam, Ketazolam, TetrazepamClonazepam, Ketazolam, Tetrazepam

Progabide, GabapentinProgabide, Gabapentin

PiracetamPiracetam

ClonidineClonidine

L-threonineL-threonine

ThymoxamineThymoxamine

Cyproheptadine, OrphenadrineCyproheptadine, Orphenadrine

• ONLY FEW CONTROLLED STUDIESONLY FEW CONTROLLED STUDIES

MOSTLY OPEN OR ANECDOTICAL OBSERVATIONSMOSTLY OPEN OR ANECDOTICAL OBSERVATIONS


Cochrane Database Syst. Rev. (2000)Cochrane Database Syst. Rev. (2000)

- - To assess the effectiveness and safety of antispastic drugs in To assess the effectiveness and safety of antispastic drugs in patients with SCIpatients with SCI

-- 9 out of 53 parallel and crossover studies (up to 1998) included9 out of 53 parallel and crossover studies (up to 1998) included

• 2 studies (placebo controlled) showed a significant effect of 2 studies (placebo controlled) showed a significant effect of intrathecal baclofenintrathecal baclofen in reducing spasticity (Ashworth - ADL) in reducing spasticity (Ashworth - ADL)

• 1 study (placebo controlled) showed a significant effect of 1 study (placebo controlled) showed a significant effect of tizanidinetizanidine in improving Ashworth scale but not ADL in improving Ashworth scale but not ADL

• No significant evidence for the other drugs (Gabapentin, No significant evidence for the other drugs (Gabapentin, Clonidine, Diazepam, oral Baclofen)Clonidine, Diazepam, oral Baclofen)


Neurolytic AgentsNeurolytic Agents

• Phenol and alcohol injections may be used to induce a focal chemodenervation by:

- protein denaturation

- non-selective tissue destruction

(nerve coagulation - muscle necrosis)

- Wallerian degeneration

• Motor nerve blockMotor nerve block

Motor point blockMotor point block


Phenol and Alcohol (1)Phenol and Alcohol (1)

• INDICATIONS:INDICATIONS:

focal spasticity - proximal muscles (lower limb)focal spasticity - proximal muscles (lower limb)

• CLINICAL EFFECTSCLINICAL EFFECTS

Reduction of muscle tone (and clonus) without impairment Reduction of muscle tone (and clonus) without impairment of strength and voluntary contraction. Long duration.of strength and voluntary contraction. Long duration.

• SIDE EFFECTSSIDE EFFECTS

sensory damage (dysesthesia, causalgia, neuralgic pain)sensory damage (dysesthesia, causalgia, neuralgic pain)

tissue damage (edema, venous thrombosis)tissue damage (edema, venous thrombosis)

• NO CONTROLLED FUNCTIONAL DATA NO CONTROLLED FUNCTIONAL DATA



BOTULINUM TOXINBOTULINUM TOXINPotent neurotoxin Potent neurotoxin

7 serotypes (A-G) with different antigenic properties 7 serotypes (A-G) with different antigenic properties reversible block of Acetylcholine release reversible block of Acetylcholine release


BOTULINUM TOXINBOTULINUM TOXINMechanism of actionMechanism of action


BTX e SPASTICITA’BTX e SPASTICITA’IndicazioniIndicazioni

• Trattamento della Trattamento della spasticità focalespasticità focale, cioè di limitati , cioè di limitati gruppi muscolari la cui iperattività o ipertonia gruppi muscolari la cui iperattività o ipertonia interferisce con lo svolgimento di specifiche attività interferisce con lo svolgimento di specifiche attività ‘funzionali’ statiche o dinamiche‘funzionali’ statiche o dinamiche

• Lo scopo è ottenere un Lo scopo è ottenere un effetto localeeffetto locale, in assenza di , in assenza di effetti sistemicieffetti sistemici

• Controindicazioni: Controindicazioni:

- mancanza di un’adeguata attività dinamica- mancanza di un’adeguata attività dinamica

- presenza di contratture fisse o deformità- presenza di contratture fisse o deformità


BTX e SPASTICITA’BTX e SPASTICITA’Possibili obiettiviPossibili obiettivi

E’ fondamentale la selezione dei E’ fondamentale la selezione dei pazientipazienti e dei e dei muscolimuscoli bersaglio e l’identificazione degli bersaglio e l’identificazione degli obiettiviobiettivi terapeutici terapeutici

• Prevenzione complicazioni (evitare chirurgia)Prevenzione complicazioni (evitare chirurgia)

• Controllo del dolore Controllo del dolore

• Facilitazione dell’igiene e/o assistenzaFacilitazione dell’igiene e/o assistenza

• Miglioramenti funzionaliMiglioramenti funzionali- adattabilità ortesi, ampliamento ROM - adattabilità ortesi, ampliamento ROM

- incremento autonomia (controllo motorio, appoggio, autonomia) - incremento autonomia (controllo motorio, appoggio, autonomia)


BTX e SPASTICITA’BTX e SPASTICITA’Effetti principaliEffetti principali

• Riduzione dell’iperattività muscolare:Riduzione dell’iperattività muscolare:- - riflesso tonico da stiramento (Ashworth Scale) riflesso tonico da stiramento (Ashworth Scale)

doloredolore

-- ‘range’ di movimento passivo ‘range’ di movimento passivo

• Evidenze neurofisiologiche:Evidenze neurofisiologiche:

- modificazioni attività riflesse spinali- modificazioni attività riflesse spinali

- effetti di tipo centrale ?- effetti di tipo centrale ?


BTX e SPASTICITA’BTX e SPASTICITA’Effetti principaliEffetti principali

• Modificazioni funzionali:Modificazioni funzionali:

- scale di autovalutazione (patient/caregiver)- scale di autovalutazione (patient/caregiver)

- scale di valutazione funzionale - scale di valutazione funzionale

(ADL, FIM, Rivermead)(ADL, FIM, Rivermead)

- test motori - test motori

(Frenchay Arm test, reaching, tapping)(Frenchay Arm test, reaching, tapping)

- analisi EMG/Video del cammino- analisi EMG/Video del cammino

INCERTEZZA SULLE MISURE DI OUTCOMEINCERTEZZA SULLE MISURE DI OUTCOME


BTX e SPASTICITA’BTX e SPASTICITA’Problemi metodologiciProblemi metodologici

• Sede d’iniezione: Quali criteri ??Sede d’iniezione: Quali criteri ??valutazione clinica e/o infiltrazione EMG-guidata valutazione clinica e/o infiltrazione EMG-guidata

- pattern MUPs- pattern MUPs

- localizzazione punto motore- localizzazione punto motore

- ‘turns amplitude analysis’- ‘turns amplitude analysis’

- stimolazione elettrica- stimolazione elettricaChilders et al., 1996 - Finsterer et al., 1997Childers et al., 1996 - Finsterer et al., 1997

• Numero iniezioni e volume diluizioneNumero iniezioni e volume diluizione ?? ??


BTX e SPASTICITA’BTX e SPASTICITA’Problemi metodologiciProblemi metodologici

• Dosaggio ??Dosaggio ??

- l’entità (ma non la durata) del miglioramento - l’entità (ma non la durata) del miglioramento funzionale può essere dose-dipendentefunzionale può essere dose-dipendente

Wissel et al., 1999; Hyman et al., 2000; Smith et al., 2000;Wissel et al., 1999; Hyman et al., 2000; Smith et al., 2000;

Bakheit et al., 2000Bakheit et al., 2000

- problema della - problema della ‘immunoresistenza’‘immunoresistenza’

- ‘basse dosi’ in associazione a procedure- ‘basse dosi’ in associazione a procedure

riabilitativeriabilitative


BTX e SPASTICITA’BTX e SPASTICITA’Trattamenti concomitantiTrattamenti concomitanti

• La stimolazione elettrica o l’attività muscolare potenzia l’attività La stimolazione elettrica o l’attività muscolare potenzia l’attività della tossinadella tossina

Hesse et al., 1995 e 1998, Eleopra et al. 1997Hesse et al., 1995 e 1998, Eleopra et al. 1997


BTX e SPASTICITA’BTX e SPASTICITA’Follow-upFollow-up

• Efficacia nel tempo del trattamento ??Efficacia nel tempo del trattamento ??

- analogia con altre indicazioni- analogia con altre indicazioni

Lagalla et al. 2000 Lagalla et al. 2000

- efficacia invariata a 3 anni in pz. con ‘stroke’- efficacia invariata a 3 anni in pz. con ‘stroke’

dose invariata, > intervallodose invariata, > intervallo



SURGICAL TECHNIQUES SURGICAL TECHNIQUES in Spasticityin Spasticity

• Objective:Objective: to treat permanently static or dynamic to treat permanently static or dynamic consequernces opf UMN sundrome in stable patientsconsequernces opf UMN sundrome in stable patients

• Timing:Timing: early and before severe and fixed deformities early and before severe and fixed deformities

• Methods:Methods: specific interventions for individual specific interventions for individual muscle/jointsmuscle/joints- TENDON LENGTHENING- TENDON LENGTHENING- INTRAMUSCULAR LENGTHENING- INTRAMUSCULAR LENGTHENING- TENDON TRANSFER- TENDON TRANSFER- NEURECTOMY- NEURECTOMY


Management of SpasticityManagement of Spasticity

REGIONALREGIONALIT/BACLOFENIT/BACLOFEN

NERVE BLOCKSNERVE BLOCKS

MEDICALMEDICALTHERAPYTHERAPY

PHYSICAL PHYSICAL THERAPYTHERAPY

Treat muscle overactivityTreat muscle overactivitywith different strategieswith different strategies

FOCALFOCALBTXBTX

INJECTIONSINJECTIONS

GENERALGENERALORALORAL

DRUGSDRUGS

Prevent:Prevent:- provocative factors or- provocative factors or noxious stimuli noxious stimuli (medication if necessary)(medication if necessary)- delayed consequences- delayed consequences(surgery if necessary)(surgery if necessary)

Documents

S P A S T I C I T Y D.S.N.V. - UniGE Motor disorder characterized by velocity dependent increase in tonic stretch reflexes and exaggerated tendon jerksMotor