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S PA S T I C I T Y
• Motor disorder
characterized by
velocity dependent
increase in tonic
stretch reflexes and
exaggerated tendon
jerks
D.S.N.V. - UniGE
UPPER MOTONEURONE
SYNDROME
• Negative phenomena
- Weakness
- Fatigability
- Reduced MUs
recruitment
- Reduced dexterity
• Positive phenomena
- Tone increase
- Stretch hyperreflexia
- Clonus
- Flexor-extensor spasms
- Abnormal cutaneous r.
- Babinski sign
- Cocontraction/Dystonia
D.S.N.V. - UniGE
Higher
Centres
Descending
+
Peripheral
Afferents
+
-
Spinal Cord
Circuitry
Pathways
Skeletal
Muscle
-
D.S.N.V. - UniGE
SPASTICITY and UMN Syndrome
Pathophysiological Mechanisms
• Defective Inhibition
 MNs
Postsynaptic  MNs inhibition
Presynaptic Ia inhibition
Excitatory group II INs
• Defective Excitation
Inhibitory Ia-INs ‘ Reciprocal’
Inhibitory Ib- INs ‘Autogenetic’
Renshaw cells ‘Recurrent’
D.S.N.V. - UniGE
SPASTICITY
Ia Pre-synaptic Inhibition
D.S.N.V. - UniGE
SPASTICITY
Ia Reciprocal Inhibition
D.S.N.V. - UniGE
SPASTICITY
Interneuronal Excitability
D.S.N.V. - UniGE
SPASTICITY and UMN Syndrome
Pathophysiological Mechanisms
• Motor Units changes
–
–
–
–
–
collateral sprouting
transynaptic degeneration
dendrite shortening
silent synapses activation
denervation supersensitivity
• Changes of Stiffnes and
muscle properties
D.S.N.V. - UniGE
Muscle & Nerve suppl 6 - 1997
D.S.N.V. - UniGE
TREATMENT of SPASTICITY
Therapeutic Objectives
• TECHNICAL:
- Promote: TONE REDUCTION
- Improve: RANGE of MOTION, JOINT POSITION
- Facilitate: REHABILITATION
• FUNCTIONAL:
- Improve: GAIT, HYGIENE, ADL, EASE of CARE
- Reduce: SPASMS, PAIN
D.S.N.V.- UniGE
PHARMACOLOGIC TREATMENT
OF SPASTICITY
• Recommended when spasticity produces a clinical disability
by interfering with posture, motor capacity, nursing, ADL
• Indicated when muscle overactivity is diffusely distributed
(spinal > cerebral)
• Timed in the early stages to prevent permanent
musculoskeletal deformities or contractures
• The goal is to decrease spinal reflex excitability by:
- reducing the release of excitatory neurotransmitters
- potentiating the activity of inhibitory circuits
D.S.N.V.- UniGE
NEUROTRANSMITTERS AND
PHYSIOLOGICAL MECHANISMS
INVOLVED IN SPASTICITY
GABA
Glycine
Glutamate
EAAs
Noradrenaline
Serotonine
D.S.N.V. - UniGE
DIAZEPAM
• Aumenta l’affinità del
GABA per il suo
recettore ionoforico
(GABA a)
-
-
Livello postsinaptico: aumento
conduttanza Cl,
iperpolarizzazione, inibizione
postsinaptica
Livello presinaptico: aumento
conduttanza Cl,
depolarizzazione, inibizione
rilascio aminoacidi eccitatori
D.S.N.V. - UniGE
BACLOFEN
• Stimolazione recettori
GABA b (metabotropici)
- Livello postsinaptico: aumento
conduttanza K,
iperpolarizzazione cellulare,
inibizione
- Livello presinaptico: blocco dei
canali del Ca, alterazione
liberazione aminoacidi eccitatori
D.S.N.V. - UniGE
D.S.N.V. - UniGE
DIAZEPAM (2)
• CLINICAL EFFECTS:
- Reduction of resistance to stretch (increased range of motion)
- Reduction of deep tendon reflexes and of painful spasms
• SIDE EFFECTS:
- Sedation & drowsiness, Attention & memory impairment
- Weakness amd motor incoordination
- Tolerance, dependency (withdrawal phenoemena)
• INDICATIONS: SCI - MS (possible: TBI - CP - CVA)
• EFFICACY SHOWN BY DOUBLE-BLIND PROTOCOLS IN SC
LESIONS (POSSIBLE STRENGTH-GAIT DETERIORATION)
D.S.N.V. - UniGE
BACLOFEN (2)
• CLINICAL EFFECTS:
- Reduction of flexor-extensor spasms
- Reduction of mono- polysynaptic reflexes
- Reduction of sphincter hyperreflexia
• SIDE EFFECTS:
- Sedation, Drowsiness, Fatigue, Confusion, Dizziness
- Hypotonia, Ataxia
• INDICATIONS: Spinal spasticity
• EFFICACY SUFFICIENTLY DOCUMENTED IN PATIENTS
WITH SC LESIONS (LESS IN CEREBRAL)
D.S.N.V. - UniGE
INTRATHECAL BACLOFEN
• Consists of direct long-term delivery of baclofen to the
intrathecal space via an implanted programmable pump
• Indicated in patients with severe spasticity, not managed by
oral baclofen (inadequate BBB penetration, side effects) or
other oral medications
• Same clinical effects at much lower doses (1 %)
• -
Selection
Screening
Implantation
Dose adjustment & maintenance
D.S.N.V. - UniGE
INTRATHECAL BACLOFEN (2)
• Benefits have been documented by placebo-controlled
studies in severely disabled nonambulatory patients with
overactivity mainly in ther lower limbs and with flexor
spasms
• Reduction of spasticity, spasms and pain
Sleep improvement and better bladder management
• IMPROVEMENT IN QUALITY OF LIFE
• COMPLICATIONS: infection, pump dysfunction, high cost
and invasiveness
D.S.N.V. - UniGE
TIZANIDINA
• Attività 2-agonista
(spinale e sopra-spinale)
- riduce la liberazione di
aminoacidi eccitatori nel
midollo spinale
- inibisce la via coerulo-spinale
(questa via normalmente
facilita i circuiti spinali)
D.S.N.V. - UniGE
TIZANIDINE (2)
• CLINICAL EFFECTS:
- reduction of tonic stretch polysynaptic reflexes
- reduction of co- contraction
• SIDE EFFECTS:
sedation, dizziness, dry mouth, but not weakness
• INDICATIONS: MS - SCI (possible: cerebral spasticity)
• EFFICACY PROVEN BY PLACEBO-CONTROLLED
STUDIES (> DIAZEPAM IN CEREBRAL). NO DEFINITE
FUNCTIONAL CHANGES
D.S.N.V. - UniGE
DANTROLENE
• Peripheral inhibition of calcium release from sarcoplasmic
reticulum. Decreased excitation-coupling reaction.
• CLINICAL EFFECTS:
Reduction of muscle tone, phasic reflexes and spasms
Increased range of passive motion
• INDICATIONS: CVA - CP (possible: TBI - SCI -MS)
• SIDE EFFECTS:
hepatotoxicity, GE symptoms, weakness, but less sedation
D.S.N.V. - UniGE
ANTISPASTIC DRUGS
• Clonazepam, Ketazolam, Tetrazepam
Progabide, Gabapentin
Piracetam
Clonidine
L-threonine
Thymoxamine
Cyproheptadine, Orphenadrine
• ONLY FEW CONTROLLED STUDIES
MOSTLY OPEN OR ANECDOTICAL OBSERVATIONS
D.S.N.V. - UniGE
Cochrane Database Syst. Rev. (2000)
- To assess the effectiveness and safety of antispastic drugs in
patients with SCI
- 9 out of 53 parallel and crossover studies (up to 1998) included
•
2 studies (placebo controlled) showed a significant effect of
intrathecal baclofen in reducing spasticity (Ashworth - ADL)
• 1 study (placebo controlled) showed a significant effect of
tizanidine in improving Ashworth scale but not ADL
• No significant evidence for the other drugs (Gabapentin,
Clonidine, Diazepam, oral Baclofen)
D.S.N.V. - UniGE
Neurolytic 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 block
Motor point block
D.S.N.V. - UniGE
Phenol and Alcohol (1)
• INDICATIONS:
focal spasticity - proximal muscles (lower limb)
• CLINICAL EFFECTS
Reduction of muscle tone (and clonus) without impairment
of strength and voluntary contraction. Long duration.
• SIDE EFFECTS
sensory damage (dysesthesia, causalgia, neuralgic pain)
tissue damage (edema, venous thrombosis)
• NO CONTROLLED FUNCTIONAL DATA
D.S.N.V. - UniGE
BOTULINUM TOXIN
Potent neurotoxin
7 serotypes (A-G) with different antigenic properties
reversible block of Acetylcholine release
D.S.N.V. - UniGE
BOTULINUM TOXIN
Mechanism of action
D.S.N.V. - UniGE
D.S.N.V. - UniGE
BTX e SPASTICITA’
Indicazioni
• Trattamento della spasticità focale, cioè di limitati
gruppi muscolari la cui iperattività o ipertonia
interferisce con lo svolgimento di specifiche attività
‘funzionali’ statiche o dinamiche
• Lo scopo è ottenere un effetto locale, in assenza di
effetti sistemici
• Controindicazioni:
- mancanza di un’adeguata attività dinamica
- presenza di contratture fisse o deformità
D.S.N.V. - UniGE
BTX e SPASTICITA’
Possibili obiettivi
E’ fondamentale la selezione dei pazienti e dei muscoli
bersaglio e l’identificazione degli obiettivi terapeutici
• Prevenzione complicazioni (evitare chirurgia)
• Controllo del dolore
• Facilitazione dell’igiene e/o assistenza
• Miglioramenti funzionali
- adattabilità ortesi, ampliamento ROM
- incremento autonomia (controllo motorio, appoggio, autonomia)
D.S.N.V. - UniGE
BTX e SPASTICITA’
Effetti principali
• Riduzione dell’iperattività muscolare:
-
riflesso tonico da stiramento (Ashworth Scale)
dolore
-
‘range’ di movimento passivo
• Evidenze neurofisiologiche:
- modificazioni attività riflesse spinali
- effetti di tipo centrale ?
D.S.N.V. - UniGE
BTX e SPASTICITA’
Effetti principali
• Modificazioni funzionali:
- scale di autovalutazione (patient/caregiver)
- scale di valutazione funzionale
(ADL, FIM, Rivermead)
- test motori
(Frenchay Arm test, reaching, tapping)
- analisi EMG/Video del cammino
INCERTEZZA SULLE MISURE DI OUTCOME
D.S.N.V. - UniGE
BTX e SPASTICITA’
Problemi metodologici
• Sede d’iniezione: Quali criteri ??
valutazione clinica e/o infiltrazione EMG-guidata
- pattern MUPs
- localizzazione punto motore
- ‘turns amplitude analysis’
- stimolazione elettrica
Childers et al., 1996 - Finsterer et al., 1997
• Numero iniezioni e volume diluizione ??
D.S.N.V. - UniGE
BTX e SPASTICITA’
Problemi metodologici
• Dosaggio ??
- l’entità (ma non la durata) del miglioramento
funzionale può essere dose-dipendente
Wissel et al., 1999; Hyman et al., 2000; Smith et al., 2000;
Bakheit et al., 2000
- problema della ‘immunoresistenza’
- ‘basse dosi’ in associazione a procedure
riabilitative
D.S.N.V. - UniGE
BTX e SPASTICITA’
Trattamenti concomitanti
• La stimolazione elettrica o l’attività muscolare potenzia l’attività
della tossina
Hesse et al., 1995 e 1998, Eleopra et al. 1997
D.S.N.V. - UniGE
BTX e SPASTICITA’
Follow-up
• Efficacia nel tempo del trattamento ??
- analogia con altre indicazioni
 Lagalla et al. 2000
- efficacia invariata a 3 anni in pz. con ‘stroke’
dose invariata, > intervallo
D.S.N.V. - UniGE
SURGICAL TECHNIQUES
in Spasticity
• Objective: to treat permanently static or dynamic
consequernces opf UMN sundrome in stable patients
• Timing: early and before severe and fixed deformities
• Methods: specific interventions for individual
muscle/joints
- TENDON LENGTHENING
- INTRAMUSCULAR LENGTHENING
- TENDON TRANSFER
- NEURECTOMY
D.S.N.V. - UniGE
Management of Spasticity
Prevent:
- provocative factors or
noxious stimuli
(medication if necessary)
- delayed consequences
(surgery if necessary)
Treat muscle overactivity
with different strategies
MEDICAL
THERAPY
PHYSICAL
THERAPY
GENERAL
REGIONAL
FOCAL
ORAL
DRUGS
IT/BACLOFEN
NERVE BLOCKS
BTX
INJECTIONS
D.S.N.V. - UniGE