Distinguishing active from passive components of ankle plantar flexor stiffness in stroke,spinal cord injury and multiple sclerosis

Objective

Spasticity is a common manifestation of lesion of central motor pathways. It is essential for correct anti-spastic treatment that passive and active contributions to increased muscle stiffness are distinguished. Here, we combined biomechanical and electrophysiological evaluation to distinguish the contribution of active reflex mechanisms from passive muscle properties to ankle joint stiffness in 31 healthy, 10 stroke, 30 multiple sclerosis and 16 spinal cord injured participants. The results were compared to routine clinical evaluation of spasticity.

Methods

A computer-controlled robotic device applied stretches to the ankle plantar flexor muscles at different velocities (8–200 deg/s; amplitude 6°). The reflex threshold was determined by soleus EMG. Torque and EMG data were normalized to the maximal torque and EMG evoked by supramaximal stimulation of the tibial nerve. Passive resistance (the torque response to stretches) was confirmed to be a good representation of the passive stiffness also at higher velocities when transmission in the tibial nerve was blocked by ischemia.

Results

Passive torque tended to be larger in the neurological than in the healthy participants, but it did not reach statistical significance, except in the stroke group (p < 0.05). Following normalization to the maximal stimulus-evoked torque, the passive torque was found to be significantly larger in neurological participants identified with spasticity than in non-spastic participants (p < 0.01). There was no significant difference in the reflex threshold between the healthy and the neurological participants. The reflex evoked torque and EMG were significantly larger in all neurological groups than in the healthy group (p < 0.001). Twenty three participants with evidence of hypertonia in the plantar flexors (Ashworth score ? 1) showed normal reflex torque without normalization. With normalization this was only the case in 11 participants. Increased reflex mediated stiffness was detected in only 64% participants during clinical examination.

Conclusion

The findings confirm that the clinical diagnosis of spasticity includes changes in both active and passive muscle properties and the two can hardly be distinguished based on routine clinical examination.

Significance

The data suggest that evaluation techniques which are more efficient in distinguishing active and passive contributions to muscle stiffness than routine clinical examination should be considered before anti-spastic treatment is initiated.     

Modulation of monosynaptic transmission by presynaptic inhibition during fictive locomotion in the cat

The effect of multisensory inputs onto the presynaptic inhibitory pathways affecting IA terminals was studied during fictive locomotion in decerebrated cats. The effect was evaluated from changes in amplitude of the monosynaptic excitatory postsynaptic potential (EPSP) measured in lumbosacral motoneurones. Responses were grouped and averaged according to their timing within the step cycle divided into five bins. Presynaptic inhibition was evoked by stimulating group I afferents from the posterior biceps-semitendinosus (PBSt) muscles and one of three cutaneous nerves: superficial peroneal (SP), sural and saphenous. Statistical analysis was applied to compare (1) EPSPs conditioned by PBSt input alone and those conditioned by the combined PBSt and cutaneous inputs, and (2) each bin dividing the step cycle to disclose phase-dependent changes. Results from 19 motoneurones showed that: (1) there was a significant phase-dependent modulation in EPSP amplitude (by 25%) with the maximum usually occurring during the depolarized phase; (2) PBSt alone reduced the EPSP amplitude (by 21%) in 3.2 bins on average; (3) combined PBSt and cutaneous stimuli further modified (up or down) the EPSP amplitude in half the trials but only in one to two bins; and (4) the most efficient cutaneous nerve (SP) usually decreased the PBSt-evoked reduction in EPSP size. Minimal changes in membrane input resistance suggest that the EPSP modifications were mostly due to presynaptic inhibition. Results indicate that muscle afferents can induce an important phase-dependent presynaptic inhibition of monosynaptic transmission and that concomitant activation of cutaneous afferents can alter this inhibition but only for a restricted part of the step cycle.     

Electromyographic assessment of spasticity

We define the concept of muscle tone and describe the signs and symptoms of its alteration in spasticity. In assessing muscle tone it is important to consider all the inputs and outputs affecting it, using biomechanical-EMG techniques for measuring active tone. We list the various features of the myotatic and defence reflexes that are altered in spastics and analyze the altered parameters in relation to the tonic reflexes. The degree of displacement, the position from which it is initiated and the velocity of displacement constitute a specific, sensitive and reliable criterion. We report the results of a personal study of these reflexes and of the shortening reflexes.

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Sommario Dopo aver definito, anche in senso semeiologico, il concetto di tono muscolare, gli AA sottolineano l'importanza di una valutazione che tenga calcolo al momento stesso dell'esame di tutti gli apporti afferenti e discendenti che influiscono su di esso. Ciò può essere fatto adottando le tecniche biomeccaniche-emg di misura del tono attivo. Dopo aver elencato i vari aspetti dei riflessi miotatici e di difesa che vengono modificati nella spasticità gli AA analizzano i parametri alterati in rapporto ai riflessi tonici. Di valore specifico, sensibile e attendibile appare il grado di spostamento, la posizione iniziale dal quale viene effettuato nonché la velocità di spostamento. Vengono poi illustrati i risultati ottenuti a carico di tali riflessi e di quelli di accorciamento sulla base di ricerche personali.

     

Long-term results of selective dorsal rhizotomy for hereditary spastic paraparesis

Pure hereditary spastic paraparesis usually presents with progressive weakness and spasticity of the legs, which is similar to spastic cerebral palsy. In this study selective dorsal rhizotomy (SDR) was performed to improve the spasticity of pure hereditary spastic paraparesis and the long-term results were followed. A series of four patients with pure hereditary spastic paraparesis diagnosed by a multidisciplinary team received SDR. The dorsal rootlets from the L2 to S1 levels were selectively resected under electrophysiological monitoring. The patients were followed up for more than 2 years to evaluate the outcome of surgery. There was a significant reduction in muscular spasm after SDR. Standing and walking stability were improved in all patients which led to improvement in walking posture and longer walking distance without assistance. No urinary retention, cerebrospinal fluid leak, surgical infection or kyphosis occurred. For severe pure hereditary spastic paraparesis, SDR can reduce muscle spasm and improve standing and walking stability. These results were stable throughout follow-up. SDR performed at the level of the conus medullaris through a laminectomy from T12 to L1 or L1 to L2 requires a shorter incision, laminectomy of fewer segments, and has a shorter operation time than the usual method (laminectomy from L2 to S1). Intraoperative electrophysiological monitoring is helpful to discriminate abnormal rootlets and protect sphincter function.     

Effect of diazepam and desmethyldiazepam in spasticity and rigidity

Benzodiazepines are known to reduce increased muscle stretch reflexes. To investigate the relationship between the necessary plasma concentrations of diazepam and its major metabolite desmethyldiazepam on the one hand and the phasic and tonic ankle reflex activity on the other, 10 mg diazepam was given intravenously to nine patients, seven with spasticity due to multiple sclerosis and two with parkinsonian rigidity. Diazepam and desmethyldiazepam both had a normalizing effect on the increased phasic ankle reflex seen in spasticity. No effect was observed on the increased tonic reflexes in rigidity. The concentrations of diazepam necessary to reduce spasticity ranged between 300-2,200 mg/l and were so high that drowsiness did occur. However, the study may indicate that desmethyldiazepam has a higher potency and a more long lasting effect on the increased phasic reflexes than diazepam.     

Correlation of quantitative measures with the modified Ashworth scale in the assessment of plantar flexor spasticity in patients with traumatic brain injury

This study of plantar flexor spasticity describes relationships among a traditional qualitative spasticity scale, three potential quantitative spasticity measures and a measure of voluntary ankle muscle function. Thirty-four volunteer adult patients with traumatic brain injuries participated. There were 28 males and 6 females; the mean age was 30.3 years. A battery of five randomly sequenced tests was performed for each subject on one ankle. Tests were: modified Ashworth scale (MAS) scoring; H-reflex testing with and without Achilles tendon vibration; H-reflex testing with and without dorsiflexor contraction; reflex threshold angle and timed toe tapping (TTT). Twenty-six subjects returned to have the second ankle tested, resulting in 60 ankles for the analyses. Spearman's coefficients for correlation of quantitative spasticity measures with MAS scores ranged from 0.39 to 0.49 with associated probabilities 0.002. Pearson coefficients for correlation of quantitative spasticity measures with TTT scores were lower but also significant (P 0.07). Multiple correlation for the set of quantitative measures yieldedR = 0.614 (P < 0.001) with MAS scores andR = 0.365 (P = 0.045) with TTT scores. These findings reveal statistically significant relationships of low to moderate strength among potential quantitative spasticity measures, a traditional qualitative spasticity scale and a simple measure of voluntary ankle muscle function. Understanding these relationships is an essential part of the ongoing search for quantitative spasticity measures.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.     

Spastic dystonia in stroke subjects: prevalence and features of the neglected phenomenon of the upper motor neuron syndrome

ObjectiveSpastic dystonia is one of the positive phenomena of the upper motor neuron syndrome (UMNS). It is characterised by the inability to relax a muscle leading to a spontaneous, although stretch-sensitive, tonic contraction. Although spastic dystonia is a recognized cause of muscle hypertonia, its prevalence among hypertonic muscles of stroke subjects has never been investigated. Differently from spasticity, which is an exaggerated stretch reflex, spastic dystonia is viewed as an efferent phenomenon, due to an abnormal central drive to motoneurons.MethodsIn 23 hemiparetic stroke subjects showing increased muscle tone of wrist flexors, surface EMG was used to investigate the presence of spontaneous, stretch-sensitive EMG activity in flexor carpi radialis.ResultsSpontaneous, stretch-sensitive EMG activity was found in 17 subjects. In the remaining 6 subjects, no spontaneous EMG activity was found.ConclusionsThe majority of stroke subjects is affected by spastic dystonia in their hypertonic wrist flexor muscles. Only a minority of subjects is affected by spasticity.SignificanceTo stop spastic dystonia from being the neglected aspect of UMNS, it is essential to link its definition to increased muscle tone, as occurred for spasticity. Recognizing the real phenomena underling muscle hypertonia could improve its management.     

Spinal interneurones; how can studies in animals contribute to the understanding of spinal interneuronal systems in man?

The first part of this review deals with arguments that the essential properties and organization of spinal interneuronal systems in the cat and in man are similar. The second part is concerned with the possibility that some interneuronal systems may be responsible for motor disturbances caused by spinal cord injuries and that these interneurones may be defined. This possibility is discussed with respect to the hyperexcitability of -motoneurones and the exaggeration of stretch reflexes in spastic patients. To this end, what is known about cat spinal interneurones and about the neuronal basis and pharmacological treatment of spasticity, is put together. Interneurones in di- and trisynaptic reflex pathways from group II muscle afferents are singled out, since they are depressed by the ₂ noradrenaline receptor agonists clonidine and tizanidine, which is a critical feature of interneurones expected to contribute to exaggerated stretch reflexes which are reduced by ₂ noradrenaline receptor agonists. Recent observations that reflex excitation of extensor motoneurones from group II afferents is enhanced in spastic patients and that the pathologically strong reflex actions of group II afferents are reduced by clonidine and tizanidine support this proposal. On the other hand, a lack of effect of clonidine and tizanidine upon other types of excitatory or inhibitory interneurones argues against any major contribution of such interneurones to the abnormally strong responses of -motoneurones to muscle stretch.     

GABA(A) receptor-mediated presynaptic inhibition on glutamatergic transmission

We investigated the functional roles of presynaptic GABA_A receptors on excitatory nerve terminals in contributing to spontaneous and action potential-evoked glutamatergic transmission to rat hippocampal CA3 pyramidal neurons. Single CA3 neurons were mechanically isolated with adherent nerve terminals, namely the ‘synaptic bouton preparation’, and spontaneous glutamatergic excitatory synaptic potentials (sEPSCs) and EPSCs evoked by focal electrical stimuli of a single presynaptic glutamatergic boutons (eEPSCs) were recorded using conventional whole-cell patch recordings. Selective activation of presynaptic GABA_A receptors on these excitatory nerve terminals by muscimol, markedly facilitated sEPSCs frequency but inhibited eEPSC amplitude. The facilitation of sEPSC frequency was completely occluded by GABA_A receptor-Cl⁻ channel blockers bicuculline or penicillin (PN). PN itself concentration-dependently inhibited the GABA_A receptor response induced by bath application of muscimol, but had no effect on the glutamate receptor response. In addition, pretreatment with a blocker of the Na⁺, K⁺, 2Cl⁻ co-transporter type 1 (NKCC-1), bumetanide, prevented the muscimol-induced inhibition of eEPSCs. The results indicate that activation of presynaptic GABA_A receptors directly depolarizes glutamatergic excitatory nerve terminals and thereby differentially modulates sEPSCs and eEPSCs.     

Botulinum toxin type A for upper limb spasticity following stroke: an open-label study with individualised, flexible injection regimens

Abstract Current antispastic medications are unsatisfactory for spasticity treatment, but botulinum toxin type A (BTX-A) shows promise as a new therapeutic option. This open-label, prospective study aimed to assess the effectiveness of BTX-A in improving functional mobility in the early post-stroke population using an individualised, flexible range of doses and targeted muscle groups. Twenty-one stroke patients (13 male, 8 female) were enrolled and injected with BTX-A (Botox, Allergan, mean dose: 255 U; range: 185–300) according to individual spasticity patterns. Assessments were made at baseline and weeks 2, 4, 6, 10 and 16 post-treatment. Outcome measures comprised: Modified Ashworth Scale (MAS), finger flexion scale (Bhakta), MRC scale, Physicians Rating Scale (PRS), Nine Hole Peg Test (9HPT), Motor Assessment Scale, Clinical Global Impression (CGI), Global Assessment of Spasticity (GASS) and Visual Analogue Scale (VAS) for pain assessment. Statistically significant improvements in muscle tone as determined by the MAS were found in all areas (except arm) till week 16 (p<0.05). Finger positioning improved for the study duration, whilst muscle power increased only slightly in specific muscles. PRS revealed significant improvements to week 10 and slight improvement in 9HPT performance in selected patients was observed. Motor Assessment Scale results were statistically significant for arm, hand and advanced hand functions, although the overall functional benefit was mild. GASS and CGI results also showed improvement. Pain was present only in 11 patients and did not significantly improve following treatment. Individualised BTX-A injection regimens may be an effective, reversible and safe new treatment option for patients with spasticity. Nevertheless, functional improvement may be reached only in selected patients.     

A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot

Abstract Botulinum toxin A (BTX) injections have been used successfully in the treatment of post-stroke foot spasticity, but the optimal dose-response relationship for selected muscles has yet to be established. The aim of this study was to outline beneficial and unwanted effects of three different doses of BTX in the treatment of spastic foot. In this randomised, double-blind, dose-ranging study, 45 spastic feet were randomly allocated to one of three groups, each of which was treated with a different dosage of BTX. The doses were decided on the basis of suggestions in the literature. Outcome measures (Modified Ashworth Scale, Medical Research Council Scale, gait assessment, presence of Achilles tendon clonus, Visual Analogue Scales for Gait Function and Pain, Adverse Effects scale) were applied at baseline, 4 weeks and 4 months after treatment. All the groups showed significant scales scores improvements after treatment with BTX. Group II (mean BTX total dose: 322 U) and Group III (mean BTX total dose: 540 U) showed a greater and more prolonged response than Group I (mean BTX total dose: 167 U). Group III showed the highest rate of adverse effects 4 weeks post-treatment. BTX injections constitute a useful and safe method of improving post-stroke foot spasticity, associated pain, gait speed and function. In particular, the medium BTX dosages (320 UI spread over 2–5 muscles) were found to be both safe and effective in producing long-lasting improvement of spastic foot dysfunction.     

Autonomic cardiovascular reflexes in pregnancy. A longitudinal study

Cardiovascular reflexes were studied in 22 healthy women before they were pregnant, once during each pregnancy trimester and after delivery to evaluate the effect of pregnancy on autonomic control of haemodynamics. The Valsalva manoeuvre, the deep breathing test, the orthostatic test and the isometric handgrip test were used to assess changes in autonomic nervous function. We found that pregnancy altered the heart rate response in the Valsalva manoeuvre, the deep breathing test and the orthostatic tests. The deep breathing difference (p = 0.03) and max/min ratio (p = 0.03) decreased in pregnancy, whereas standing heart rate increased (p < 0.0001). Both the systolic and diastolic blood pressure increased after standing up during pregnancy. The circulatory responses to isometric exercise were not affected by pregnancy. The results show that parasympathetic respon-siveness is decreased in pregnancy and that it returns to normal after delivery.     

The relation between spasticity and muscle behavior during the swing phase of gait in children with cerebral palsy

There is much debate about how spasticity contributes to the movement abnormalities seen in children with spastic cerebral palsy (CP). This study explored the relation between stretch reflex characteristics in passive muscles and markers of spasticity during gait. Twenty-four children with CP underwent 3D gait analysis at three walking velocity conditions (self-selected, faster and fastest). The gastrocnemius (GAS) and medial hamstrings (MEHs) were assessed at rest using an instrumented spasticity assessment that determined the stretch-reflex threshold, expressed in terms of muscle lengthening velocity. Muscle activation was quantified with root mean square electromyography (RMS-EMG) during passive muscle stretch and during the muscle lengthening periods in the swing phase of gait. Parameters from passive stretch were compared to those from gait analysis.In about half the children, GAS peak muscle lengthening velocity during the swing phase of gait did not exceed its stretch reflex threshold. In contrast, in the MEHs the threshold was always exceeded. In the GAS, stretch reflex thresholds were positively correlated to peak muscle lengthening velocity during the swing phase of gait at the faster (r = 0.46) and fastest (r = 0.54) walking conditions. In the MEHs, a similar relation was found, but only at the faster walking condition (r = 0.43). RMS-EMG during passive stretch showed moderate correlations to RMS-EMG during the swing phase of gait in the GAS (r = 0.46–0.56) and good correlations in the MEHs (r = 0.69–0.77) at all walking conditions. RMS-EMG during passive stretch showed no correlations to peak muscle lengthening velocity during gait.We conclude that a reduced stretch reflex threshold in the GAS and MEHs constrains peak muscle lengthening velocity during gait in children with CP. With increasing walking velocity, this constraint is more marked in the GAS, but not in the MEHs. Hyper-activation of stretch reflexes during passive stretch is related to muscle activation during the swing phase of gait, but has a limited contribution to reduced muscle lengthening velocity during swing. Larger studies are required to confirm these results, and to investigate the contribution of other impairments such as passive stiffness and weakness to reduced muscle lengthening velocity during the swing phase of gait.     

A randomized comparative study of two methods for controlling Tendo Achilles contracture in Duchenne muscular dystrophy

A 30-month prospective randomized study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was done to compare the effect of passive stretching combined with the use of night splints (group A) or passive stretching (group B) on the evolution of Tendo Achilles contractures. Assessments were based on the methodology of Scott et al. (Muscle Nerve 1982;5:291-301)Analysis of the pattern and mechanism of dropout was done to eliminate bias between the two groups. Logistic regression showed that Tendo Achilles contracture was the most important variable (P=0.0020) for dropout. Methods of statistical analysis for longitudinal data avoiding induced serial correlations were used in the analysis. The expected annual change in Tendo Achilles contracture was found to be 23% less in group A than in group B after equalization for total muscle strength (%MRC).     

A study of the quantal (all-or-none) change in reflex latency produced by opiate analgesics

The properties of opiate-induced changes of tail-flick latency were studied in the rat.

(1) Morphine and pentazocine produced a stepwise increase in latency which rose from near baseline to cut-off (usually greater than 20 sec) in less than 30 sec. Abrupt return to pre-treatment latencies was observed either spontaneously or when the rat was back-titrated with the narcotic antagonist naloxone.

(2) The proportion of rats showing this stepwise change increase with increasing dose; however, the step itself was independent of dose. The same step was produced by a slow, constant infusion of morphine but was not produced by ice-water stress or barbiturate administration.

(3) Increasing heat intensity to the tail shortened the baseline latency and raised the mean dose of morphine required to produce a step latency increase.

(4) A step increase in latency was also observed when paw withdrawal instead of tail-flick was measured.

We hypothesize that the analgesic behavior described partly defines the operating characteristics of an intrinsic endorphin-mediated analgesia system which mediates narcotic suppression of withdrawal reflexes.