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Home , Clonus, Spasticity, Spinal neuron

REVIEW

Clonus: definition, mechanism, treatment

Ismail Boyraz1, Hilmi Uysal2, Bunyamin Koc1, Hakan Sarman3

1Physical Medicine and Rehabilitation, Abant Izzet Baysal University, Bolu, 2Neurology, Akdeniz University Hospital, Antalya, 3Orthope- adics Department, Abant Izzet Baysal University, Bolu; Turkey

ABSTRACT

Clonus is involuntary and rhythmic muscle contractions caused by a permanent lesion in descending motor . Clonus may be found at the ankle, patella, triceps surae, wrist, jaw, biceps brachii. In general, clonus may occur in any muscle with a frequency of 5-8 Hz and the average period of oscillations of the ankle clonus is approximately 160–200 ms. Plantar flexion (PF) comprises 45% of the period, dorsifleksion (DF) comprises 55% of the period. The first beat is always longer, with the time shortening in conti- nuing beats and becoming stable in the 4th or 5th period. The exact mechanism of clonus remains unclear. Two different hypotheses have been asserted regarding the development of clonus. The most widely accepted explanation is that hyperactive stretch reflexes in clonus are caused by self-excitation. Another alternative explana- Corresponding author: tion for clonus is central generator activity that arises as a con- Ismail Boyraz sequence of appropriate peripheral events and produces rhythmic Physical Medicine and Rehabilitation stimulation of the lower motor neurons. The durations of clonus Hospital, Abant Izzet Baysal University burst were found longer than the durations of Soleus medium-la- tency reflex (MLR). There is a similarity in their nature, although Aibu Ftr Hospital Karacasu, the speed and cause of the stretch of triceps surae differ in the Bolu 14100Turkey MLR and the clonus, and there is a sufficient period of time for Phone: +90 505 469 17 28; group II afferents and for other spinal mechanisms to be involved Fax: +90 374 262 91 90; in the clonus, together with Ia afferents. Clonus can be treated by E-mail: [email protected] using , applying cold, botox or phenol injections. Key words: , , upper motor disorder, gait disorder

Original submission: 04 September 2014; Revised submission: 22 December 2014; Accepted: 05 January 2015.

Med Glas (Zenica) 2015; 12(1):19-26

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INTRODUCTION occurs in the lower limb under like circumstan- ces (7). But the wrist-phenomenon, provoked Clonus is involuntary and rhythmic muscle con- or spontaneous, is much more uncommon. In tractions caused by a permanent lesion in descen- general, clonus may occur in any muscle with a ding motor neurons and it is usually considered frequency of 5-8 Hz and the average period of to be a result of oscillations in the group Ia spinal oscillations of the ankle clonus is approximately stretch reflex (Figure 1). Clonus is accompanied 160–200 ms (9). Plantar flexion (PF) comprises by spasticity and other findings of reflex - exci 45% of the period, and dorsiflexion (DF) compri- tability (1). Spasticity is defined as an increa- ses 55% of the period (9). It has been shown that sed resistance to stretching caused by disorders the duration of the dorsiflexion was 88.63±10.83 involving the upper motor neurons, and clonus ms, and the duration of the PF was 71.75±6.73 is characterized by exaggerated stem and ms (9). The DF and PF comprised 55.17±3.9% spinal reflexes resulting in increased muscle tone and 44.83±3.9% of one clonus beat, respectively and involuntary . Although closely linked, (9). The first beat is always longer, with the time clonus is not seen in all patients with spasticity shortening in continuing beats and becoming (2).Clonus does not occur if the muscle is exce- stable in the 4th or 5th period. Measured the re- ssively hypertonic (2). Any mechanism or phar- fractory period only in the triceps surae muscle macological drug suppressing increased reflexes is 90-100 ms. This period may differ for other and muscle tone is also prone to block the clonus muscle groups with different central stretch re- (2). Severe clonus can interrupt sleep and prevent flex organizations, thereby resulting in different the transfer capability of the patient and result in maximum clonus frequencies (9). In order to fatigue that can decrease work performance of an reach an understanding of clonus, it is essential individual (3). It can also interfere with the po- to consider not only reflex path length but also sture and gait of the patient (4). Clonus can also and relaxation times, muscle occur in normal individuals. The plantar flexion load, activity and central exci- power is low in normal individuals (5). Clonus tability, all of which play a role in clonus (7,9). may be found at the ankle, patella, triceps surae, Dimitrijevic et al. have shown that clonus occu- wrist, jaw, biceps brachii (6-8). Jaw jerk is due to rred in the presence of a lesion involving a large supranuclear lesion of the trigeminal and portion of the lateral corticospinal tract(2). This it may occur in Amyotrophic Lateral Sclerosis observation was based on the histopathological (6).Wrist clonus in patients with hemiplegia was evaluation of specimens from patients with a le- notably described in lectures published in 1883 sion in the (CNS). They by the French neurologist Jean-Martin Charcot, reported that the frequency of clonus was con- who called the phenomenon “provoked trepida- stant in each muscle and the frequency of clo- tion”, the patients, on raising the paralyzed arm, nus did not show a tendency toward a change often experience trembling similar to that which over time (2). Rapid onset exteroceptive stimu- lations in sufficient intensity can induce clonic discharge in the muscle and not only via type Ia afferent fibers (9). Painful stimuli and cold are the leading cutaneous stimuli giving rise to and sustaining clonus. The cutaneous stimulation of the unaffected side can also produce clonus. The stimulations causing polysynaptic flexor or extensor reflexes are susceptible to produce clo- nus via nonspecific descending facilitations pro- duced by the “Jendrassik” maneuver. The stimuli activating these pathways can stop clonus (5). Clonus may even occur in the absence of any mo- vement in the extremity. The amplitude of clonus Figure 1. Ankle clonus Soleus rectified EMG and position of the ankle are displayed superimpose. Soleus muscle activity can induced and sustained by stretch can decrease be seen after ankle dorsiflexion and become attenuated over time. Cutaneous sti-

20 Boyraz et al. Clinical aspect of clonus

mulation triggered by scratching skin over the cited during muscle lengthening is now sufficient muscle will provide sufficient input to the spinal to reach threshold for motoneuron firing (16). cord to maintain the amplitude of clonus (2). Ber- This shift in threshold can be thought of as an nhard and Therman showed that proprioceptive effective increase in the feedback gain since the inputs generated with the movement of the limbs same amount of afferent input in the spastic case trigger rhythmic discharges from the motor units will result in higher motoneuron activation than in decerebrate cats (10). in a normal threshold level (17,18). According to Gottlieb and Agarwal showed that pharmaco- control theory, instability may arise in a system logical agents increasing the discharge from with a high feedback gain and significant delays, stretched muscle fibers could produce clonus in conditions both present in the ankle muscles of healthy individuals. They reported that clonus in spastic subjects (13). Hidler et al have clearly normal individuals shares common features with shown that both movement frequency and EMG those in spastic patients and possesses a limited burst frequency can be altered, and so we can band of frequency, and it is independent from the only speculate that the loads used in the mentio- loading on the extremity (11).Struppler observed ned studies were not sufficient to perturb the sy- these findings using iv succinylcholine injection, stem onto a different limit cycle orbit (19). Clo- and Marsden, Meadows, and Hodgson used IV nus was of shorter duration when more muscles adrenalin injections (12,13). were activated. In contrast, clonus was persistent when EMG activity was largely confined to the CLONUS MECHANISM synergistic triceps surae muscles (20). The exact mechanism of clonus remains uncle- Iansek found a linear relationship between the ar. Two different hypotheses have been asserted frequency of clonus and the distance between regarding the development of clonus. The most and the muscle. Mathematically, re- widely accepted explanation since the pionee- flex oscillation latency was found to be predo- ring studies by Denny-Brown (1928-1929) is that minant in determining frequency, and if there hyperactive stretch reflexes in clonus are caused was a central spinal pacemaker, it would predict by self-excitation (14). Szumski et al. observed the frequency of clonus regardless of the length that a few beats of clonus occurred after tendon of the reflex pathway (21). The findings that are tap in the wrist flexors and clonus was sustained parallel to pure peripheral self-re-excitation me- by the “Jendrassik” maneuver. They concluded chanisms are preferably coupled with high reflex that the spindles involved in clonus were abnor- arc gain (shift in threshold of motoneuron activa- mally sensitive and dynamic fusimotor neurons tion). Possible factors involved in the regulation were important motor neurons involved in elici- of clonus frequency are length of reflex arc; the ting clonus (2). Szumski and Hagbarth showed frequency of clonus can increase with the decre- the discharge of Ia afferent fibers before clonic ase in activation latency of la afferent fibers; fac- bursts on electromyographi (EMG) and these tors such as the mass and viscosity of the muscles discharges were not activated during muscle con- can affect the frequency of clonus by changing traction. They concluded that muscle spindles the activity latency of spindle relaxation (21). were stretched during muscle relaxation and re- The idea that central mechanisms may be invol- peated oscillatory movement elicited EMG acti- ved was not adopted in observations where clo- vity (5). Janell et al. reported that clonus would nus was attributed to peripheral mechanisms. The not be elicited if reflex responses were not gene- frequency of clonus changed by changing the rated against a stretch (3). Rack et al. observed mechanical load on the . The rhythmic os- that the frequency of soleus EMG activity could cillations occurring in stretched muscles in some be regulated by loading and loaded oscillatory animal preparations are assumed to be analogous movements in spastic patients, and they con- to clonus, and these oscillations were inhibited cluded that self-sustaining oscillation of stretch by the blockade of peripheral afferent fibers (22). reflex pathway resulted in clonus. In spastic su- Unsuccessful utilization of the signals from bjects, motoneuron firing threshold may decrease muscle spindles and Golgi tendon organs com- to a level in which the spindle afferent output eli- plicates imaging and regulation of muscle length

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and power and autogenic reflex pathways play a (24).Cook et al. showed that ankle dorsi-flexor major role in motor control in humans (4,23,24). remained reactively silent during the emergence The stretch reflex is a primary autogenic reflex of clonus, and the blockade of the peroneus co- and the negative feedback arc is the first line of mmunis nerve did not affect the amplitude and active resistance when the body interacts with the duration of oscillation (25). environment. In normal conditions, the gains in The character of the input-output relationship in reflex pathways were shown to be minimal. The motor neurons can be defined by the Gaussian functional behavior of the reflexes changes si- cumulative distribution function. Accordingly, gnificantly with increasing excitability of motor the synaptic current scale is linearly correlated neurons. It is believed that clonus with rhythmic with the spindle firing rate. The functional pa- or oscillatory contractions could occur in distal ttern of motor neurons is determined by both limbs where there is a change in the excitability motor unit recruitment and modulation rate. The of CNS associated with concurrent neurological single major reason for the delay in the generati- disorders and when there is an increased tenden- on of the monosynaptic reflex arc is neural con- cy toward instability (2,4,23). duction time in the reflex pathway. The delays in Hidler et al. hypothesized the coexistence of the “negative feedback” pathway possess a de- both conditions for the occurrence of clonus: re- stabilizing effect on the behavior of the system. flex pathway delay (involving distal extremity The frequency of oscillation decreases with in- muscles, displaying slow twitch properties), and creasing conduction delay (1). increasing motor excitability (decrease in Another reason for the delay in the reflex pathway excitability threshold). These two is the contractile features of the muscle. These phenomena disrupt the stability of motor neu- delays are caused by Ca dynamics, myofilament rons. The high incidence of orderly motor unit cross bridges, elasticity of the muscle fibers, and recruitment in human skeletal muscles that, due tendon compliance. In pathological conditions, to spinal trauma, are under no voluntary con- slow-twitch muscle fibers can be replaced by trol from higher centers suggests that spinal sy- fast-twitch muscle fibers. The input-output beha- stems also dominate the stereotyped excitation vior in the muscle is similar to that in low pass of human motoneurons during clonus. Thus, any filtering. Low pass filtering in the muscle or the changes in spinal neuron excitability, synaptic delays in the reflex pathway due to conduction inputs, or muscle properties due to injury were delays will affect reflex stability (24). appropriate to preserve an orderly pattern of It is believed that clonus and spasticity share a motor unit recruitment, as found during volun- common pathway; therefore, their co-occurrence tary contractions of muscles innervated from the on most, if not all, occasions is not surprising. level of injury (12,13). Orderly recruitment of The neuroaxial lesions such as or spinal motor units during clonus is ordered by size of cord injury result in a net inhibition in segmen- unit excitability. Afferent activity from the previ- tal neurons. The balance of synaptic input to ous contraction and the level of spinal excitation the motor neurons would change in favor of net were adequate to recruit most of the units during excitation. It was reported that the muscle was every contraction but were insufficient to increa- continuously active due to on-off signal during se their firing rates. None of these peripheral or rotational movement, and high tonic activity can spinal factors were sufficient to markedly disrupt be responsible for this condition. The oscillatory the recruitment order of pairs of motor units du- behavior observed in clonus is similar to closed ring clonus (4). arc oscillations seen in negative feedback control The reason for this lengthened delay in spasticity encompassing high feedback gains accompanied may be the sensitivity of muscle spindles or chan- by significant delays. ges in the passive features of the muscle. Increase Hagbarth et al. recorded medial gastrocnemius of viscoelasticity of passive tissues enlarges the Ia afferent muscle spindle discharges during clo- clonus receptive area (shaded); that is, it incre- nus caused by the stretch before muscle stretch ases the amount of combinations of motor unit and not during muscle activation. While spindle pool threshold and gain that will result in clonus activity is expected during muscle stretch, the

22 Boyraz et al. Clinical aspect of clonus

observation of muscle spindle activation in medi- disease. The shortening reaction in the ankle has al gastrocnemius is not surprising during clonus been rarely observed in patients with first motor elicited by fast stretch of PF; however, it was su- syndrome (12%) and the rate was uncommonly ggested that this would not be proven if spindle compared to disabled subjects (23). activation directly elicited or maintained clonus. Attempts have been made to change the frequ- No positive correlation was found between the ency of clonic oscillatory burst patterns in order number and frequency of power and spindle dis- to test the stretch reflex and central oscillatory charges following clonic EMG bursts. They re- theories. If clonus correlates with the stretch, ported that hyperexcitability of the stretch reflex externally applied motion frequency affects the is not centrally related for certain (26). frequency of clonus. Rack et al. observed rhyt- If repeated muscle stretch and the resulting hmic EMG activity with various frequencies in muscle spindle activation elicit clonus, tibialis response to ankle loading (16). Hidler and Rymer anterior muscle spindle activity and subsequent reported that the increase in the applied moment EMG activity should have been formed in a pa- loading produced a greater stretch on the plan- ttern following the activity of medial gastrocne- tar flexors, and this resulted in early EMG res- mius. Hagbarth et al. did not record this from the ponse with higher frequency (1). It was reported tibialis anterior (26). Janell et al. suggested that that clonus could be re-established (reset) with the synchronous discharge of muscle spindle af- the stimulation of the soleus H-reflex in the time ferents of antagonistic muscles would be unlikely frame between two successive clonic beats (28). during DF-PF of the ankle joint, although muscle Peripheral events are estimated to regulate affe- spindle activation was not measured directly (3). rent output, and such observations are commonly When synchronous activation of plantar flexors reported. On the other hand, there is no sufficient and tibialis anterior during clonus was demon- evidence to suggest that clonic EMG was only strated, the inconsistency with the origin of the caused by the recurrent stretch reflex. The obser- stretch reflex was not taken into consideration. vation of oscillatory EMG activity in the absence Cook et al reported tibialis anterior EMG acti- of synchronous repetitive peripheral inputs sup- vity synchronous with PF that could not be eli- ports the role of oscillatory neurons in the spi- minated by tibialis anterior nerve blockade, and nal cord that can be activated by many afferent they concluded that the observed tibialis anterior events (19). EMG activity could have been caused by cross- Another alternative explanation for clonus is cen- convergence due to PF (27). In addition, succe- tral generator activity that arises as a consequen- ssive plantar-dorsiflexion EMG was not observed ce of appropriate peripheral events and produces during clonus. They concluded that antagonistic rhythmic stimulation of the lower motor neurons activity was not necessary to elicit clonus and it (9). Walsh reported that clonic EMG frequencies was attributed to the repeated reflex stretch of of plantar flexors remained unchanged (14). In plantar flexors. According to the results of the their study, Dimitrijevic et al. evaluated clonus stimulation data, the investigators ruled out tibia- EMG records, ankle angle, and pressure applied lis anterior and supported repeated stretch reflex to the soles, and they investigated whether the as the cause of clonus (l). Cook et al. provided silent period between two beats of clonus was alternative explanations, suggesting that the acti- caused by loading on the spindles or by the cen- vity observed in tibialis anterior was not caused tral refractory period (2). The attempts failed to by plantar flexors, but may have been caused by change the frequency of clonus. The refractory incomplete nerve blockade (19). period was approximately 100 msec and the exci- Hidler and Rymer observed tibialis anterior EMG tatory period was approximately 60 msec, and activity synchronous with soleus and medial ga- accordingly cyclic changes in centrally regulated strocnemius activity during clonus, and they excitability constitute the basis for clonus and attributed tibialis anterior EMG activity to shor- determine its frequency. They indicated that peri- tening reaction. The shortening reaction is defi- odicity could be modified only for a short period ned as the EMG response in the shortened muscle by Ia inputs while transforming from the refrac- commonly observed in patients with Parkinson’s tory period to excitatory period (2). According

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to Dimitrijevic, the central generator is a transi- is due to the inhibition of motor neurons and/or stor providing a functional organization, and it is . The prolonged period of refractori- made up of segmental reflex activity influenced ness is caused by Renshaw cells. by peripheral, propriospinal, suprasegmental me- The results of Janell et al.and Walsh support the chanisms, proprioceptive volleys from the limb, interaction between many peripheral events and and the movement of the muscle and parts of the central mechanisms to elicit clonus (3,33). Despi- limb. The features of the central generator inclu- te the lack of an input that would produce a stret- de cyclic, regular activation at a fixed phase (2). ch in the muscles, bilateral clonic EMG activity Brune and Schenck examined H-reflex volleys was prominent in the proximal and distal limbs between two clonic bursts and reported a refrac- in the standing position without bearing weight. tory period between EMG bursts. They attribu- Clonus has been observed in the hamstring musc- ted the cessation of motor neuron activity at the les following the development of clonus in the beginning of the silent period to the refractory vastus medialis, vastus lateralis, and rectus femo- state of the motor neurons with the inhibition of ris muscles while loading in the standing position Renshaw cells after firing and lack of stimulati- and clinically after clonus in the ankle. The co- on from spindle afferents at the rest of the pe- activation of the muscles between the limbs may riod (29). Strupler, Burg, and Erbel suggested have played a role after , but that recurrent inhibition produced by Renshaw the co-activation of antagonistic muscles in the cells and autogenic inhibition by Golgi afferents same limbs also point to the convergence of the played a role in the refractory phase of the motor interneurons. A synchronous and bilateral muscle neurons and not only spindle unloading (30). Na- stretch in agonist and antagonist muscles seems than measured the refractory period only in the unlikely (3). triceps surae muscle (90-100 ms). He proposed that this period may differ for other muscle gro- TREATMENT OF CLONUS ups with different central stretch reflex organi- Clonus can be treated by using baclofen, appl- zations, thereby resulting in different maximum ying cold, botox or phenol injections (7, 9, 34- clonus frequencies (31). Wachholder and Alte- 37). Several studies in the literature have repor- nburger showed that the latency of the first clo- ted that centrally active antispastic drugs do not nic beat was same as the stretch reflex. This time have significant effects on clonus; however, some relationship did not persist in sustained clonus. studies have shown that baclofen has more dra- Therefore, they expressed that clonus was trig- matic effects than other drugs. selecti- gered by the stretch and rhythmic discharge was vely blocks group II pathways, which have a role maintained by the central factors (32). in spasticity but has no effect on clonus (38-41). The characteristic feature of clonus is synchro- In a study by Bassett and Lake on patients with nous motor discharge. It was reported that syn- lesions, spasticity and clonus chronous discharge occurred despite the input both decreased with the application of wet towels from asynchronous spindles to the clonus, musc- wrapped in crushed ice and with submergence in le geometry, and the contribution of peripheral cold water (42). Measurable functional improve- muscle factors such as the relaxation rate of the ment has been reported in association with decre- muscle (31). This indicates that the reflex is rigid- ased spasticity after cold application. Knutsson ly controlled over time and in the spatial extent who studied the kinematics of spastic gait before in the motor unit pool. It was asserted that the and after cold application, reported that a decre- discrepancy between peripheral factors and syn- ase in spasticity of antagonistic spastic plantar chronized motor unit response indicates that cen- flexors paralleled an increase in the late oscillati- tral mechanisms play a major role (3,5). It was on phase during dorsiflexion (43). Hedenberg on reported that peripheral input is essential for the the other hand, tested upper extremity functions re-activation of cyclic bursts and the overall ac- of patients with hemiplegia before and after sub- tivity is controlled by spinal mechanisms. The mergence in cold water and after cold application intermittent discharge of clonus is suggested to and noted significant improvements in functional be caused by the periods of refractoriness, which capacities (44). Dimitrijevic et al. reported no

24 Boyraz et al. Clinical aspect of clonus

changes in clonus frequencies with cold appli- of dependence on others (33). The treatment of cation (2). Miglietta showed that the longer the clonus and spasticity may be obtained by using period of cold application, the longer it took for centrally and peripherally effective mechanisms clonus to recur. The average periods of recurren- simultaneously. ce of clonus observed after 10, 20, and 30 minu- Clonus was considered to be a common presen- tes of cold application were 28 (range, 15 to 45 tation of the intrinsic oscillation of the spinal ne- minutes), 48 (range, 10 minutes to 2 hours), and ural network after a reduction in sensorial input 85 minutes (20 minutes to 6 hours), respectively related to loading and chronic loss of supraspi- (40,45). Cold application induced prolonged in- nal input. The spinal networks can be activated hibitory effects on clonus. In response to cryothe- by numerous stimulations including interventi- rapy, Boyraz et al. showed persistence of H and T ons during voluntary movements, nociceptive reflexes with prolonged latencies, as well as de- , and cutaneous synapses. Due to the creases in the stimulation threshold and H/M ra- presence of limited motor pools to elicit volun- tio, but with a marked inhibitory effect on clonus. tary movements after severe spinal cord injury, There is a persistence of ankle clonus inhibition the attempts mostly result in generalized motor even after a cooled muscle has returned to body patterns. In most cases with spinal cord injury, temperature. This phenomenon could be explai- chronic unloading occurs not only as a result of ned by an increase in the threshold of the nerve fi- the absence of supraspinal input, but also due to ber and/or a relatively prolonged refractory peri- a lack of stepping and standing. Synchronous os- od. The prolonged effect of the cold supports the cillatory motor output could be a re-organization presence of spinal neuroplasticity and adaptation of the neural network as a response to chronically in individuals with neurologic impairments (35). changing afferent and supraspinal inputs, and Thevenon showed that clonus affected the first therefore the same stimulus before injury did not metatarsal, since it was selectively triggered by cause the activation of the entire network. It must extension of the first metatarsophalangeal joint. be investigated as to whether repetitive afferent To treat clonus, they applied injecting botulinum information regarding stepping would re-modi- toxin into the peroneus muscles but failed. To fy the clonic motor firing pattern. Better results stop clonus through selective neurotomy of the in the treatment of clonus and spasticity may be gastrocnemius and soleus, Thevenon performed obtained by using centrally and peripherally ef- neurotomy of the branches of the superficial fi- fective mechanisms simultaneously. bular nerve that innervated the peroneus brevis and peroneus longus. After the , clonus of FUNDING the first metatarsal was no longer observed (35). No specific funding was received for this study. Botulinum toxin has a role in treating ankle clo- nus in neurological patients, where it interferes TRANSPARENCY DECLARATION in gait and may improve walking speed and level Competing interest: none to declare.

REFERENCES

1. Hidler JM, Rymer WZ. A simulation study of reflex 5. Szumski AJ, Burg D, Struppler A, Velho F. Activity instability in spasticity: origins of clonus. IEEE Trans of muscle spindles during muscle twitch and clonus Rehabil Eng 1999; 7:327-40. in normal and spastic human subjects. Electroencep- 2. Dimitrijevic MR, Nathan PW, Sherwood AM. Clo- halogr Clin Neurophysiol 1974; 37:589-97. nus: the role of central mechanisms. J Neurol Neuro- 6. Iodice R, Manganelli F, Dubbioso R, Ruggiero L, surg Psychiatry 1980; 43:321-32. Santoro L. Teaching video neuroimages: clonus of the 3. Beres-Jones JA, Johnson TD, Harkema SJ. Clonus lower jaw: an old sign that comes back. after human spinal cord injury cannot be attributed 2014; 82:e96. solely to recurrent muscle-tendon stretch. Exp Brain 7. Biotti D, Vighetto A. Images in clinical medicine. Res 2003; 149:222-36. Upper limb clonus. N Engl J Med 2013; 369:e12. 4. Wallace DM, Ross BH, Thomas CK. Motor unit be- 8. Walsh EG, Wright GW. Patellar clonus: an autonomo- havior during clonus. J Appl Physiol (1985) 2005; us central generator. J Neurol Neurosurg Psychiatry 99:2166-72. 1987; 50:1225-7.

25 Medicinski Glasnik, Volume 12, Number 1, February 2015

9. Uysal H, Boyraz I, Yagcioglu S, Oktay F, Kafali P, 29. Brune H, Schenck E. Neurophysiologische Untersu- Tonuk E. Ankle clonus and its relationship with the chungen über den klonus bei spastikern. Eur Arch medium-latency reflex response of the soleus by pe- Psychiatry Clin Neurosci 1960; 201:65-80. roneal nerve stimulation. J Electromyogr Kinesiol 30. Struppler A, Burg D, Erbel F. The unloading reflex 2011; 21:438-44. under normal and pathological conditions in man.J 10. Bernhard CG, Therman PO. Rhythmical activity of Biomech1973; 3:603-17. motor units in myotatic reflexes. Acta Physiol Scand 31. Nathan P, Dimitrijevic MR, Sherwood AM. Reflex 1947; 14:1-14. path length and clonus frequency. J Neurol Neurosurg 11. Gottlieb GL, Agarwal GC. Physiological clonus in Psychiatry 1985; 48:725. man. Exp Neurol 1977; 54:616-21. 32. Wachholderu K, Altenburger H. Experimentelle Un- 12. Struppler A, Schulte F, Scheininger R, Kukku M. tersuchungen zur Entstehung des Fussklonus. J Neu- Eine elektromyographische Untersuchung bei Spastik rol 1925; 84:117-21. und Rigor. Journal of Neurology 1961; 183:134-47. 33. McGuinness S, Hillan J, Caldwell SB. Botulinum 13. Marsden CD, Meadows JC, Hodgson HJ. Observati- toxin in gait dysfunction due to ankle clonus: A case ons on the reflex response to muscle vibration in man series. Neurorehabilitation 2013; 32:635-47. and its voluntary control. Brain 1969; 92:829-46. 34. Lin JP1, Brown JK, Walsh EG.Continuum of reflex 14. Walsh EG. Clonus: beats provoked by the application excitability in hemiplegia: influence of muscle length of a rhythmic force. J Neurol Neurosurg Psychiatry and muscular transformation after heel-cord lengt- 1976; 39:266-74. hening and immobilization on the pathophysiolo- 15. Beres-Jones JA, Johnson TD, Harkema SJ. Clonus gy of spasticity and clonus. Dev Med Child Neurol after human spinal cord injury cannot be attributed 1999;41:534-48. solely to recurrent muscle-tendon stretch. Exp Brain 35. Manca M, Merlo A, Ferraresi G, Cavazza S, Marchi P. Res 2003; 149:222-36. Botulinum toxin type A versus phenol. A clinical and 16. Rack PM, Ross HF, Thilmann AF. The ankle stretch neurophysiological study in the treatment of ankle reflexes in normal and spastic subjects. The response to clonus. Eur J Phys Rehabil Med 2010; 46:11-8. sinusoidal movement. Brain 1984; 107(Pt 2):637-54. 36. Thevenon A, Serafi R, Fontaine C, Grauwin MY, Bu- 17. Powers RK, Marder-Meyer J, Rymer WZ. Quantita- isset N, Tiffreau V. An unusual cause of foot clonus: tive relations between and stretch reflex spasticity of fibularis longus muscle. Ann Phys Reha- threshold in spastic . Ann Neurol 1988; bil Med 2013; 56:482-8. 23:115-24. 37. Boyraz I, Oktay F, Celik C, Akyuz M, Uysal H. Effect 18. Katz RT, Rymer WZ. Spastic hypertonia: mechani- of cold application and tizanidine on clonus: clinical sms and measurement. Arch Phys Med Rehabil 1989; and electrophysiological assessment. J Spinal Cord 70:144-55. Med 2009; 32:132-9. 19. Hidler JM, Rymer WZ. Limit cycle behavior in spa- 38. Bass B, Weinshenker B, Rice GP, Noseworthy JH, sticity: analysis and evaluation. IEEE Trans Biomed Cameron MG, Hader W, Bouchard S, Ebers GC. Ti- Eng 2000; 47:1565-75. zanidine versus baclofen in the treatment of spasticity 20. Wallace DM, Ross BH, Thomas CK. Characteristics in patients with . Can J Neurol Sci of lower extremity clonus after human cervical spinal 1988; 15:15-9. cord injury. J Neurotrauma 2012; 29:915-24. 39. Stien R, Nordal HJ, Oftedal SI, Slettebo M. The tre- 21. Iansek R. The effects of reflex path length on clonus atment of spasticity in multiple sclerosis: a double- frequency in spastic muscles. J Neurol Neurosurg blind clinical trial of a new anti-spastic drug tizanidi- Psychiatry 1984; 47:1122-4. ne compared with baclofen. Acta Neurol Scand 1987; 22. Jansen JK, Rack PM. The reflex response to sinusoi- 75:190-4. dal stretching of soleus in the decerebrate cat. J Physi- 40. Smith C, Birnbaum G, Carter JL, Greenstein J, Lublin ol 1966; 183:15-36. FD. Tizanidine treatment of spasticity caused by mul- 23. Hidler JM, Harvey RL, Rymer WZ. Frequency res- tiple sclerosis: results of a double-blind, placebo-con- ponse characteristics of ankle plantar flexors in hu- trolled trial. US Tizanidine Study Group. Neurology mans following spinal cord injury: relation to degree 1994; 44:S42-3. of spasticity. Ann Biomed Eng 2002; 30:969-81. 41. Knutsson E, Martensson A, Gransberg L. Antiparetic 24. de Vlugt E, de Groot JH, Wisman WHJ, Meskers and antispastic effects induced by tizanidine in pati- CGM. Clonus is explained from increased reflex gain ents with spastic paresis. J Neurol Sci 1982; 53:187- and enlarged tissue viscoelasticity. Journal of Biome- 204. chanics 2012; 45:148-55. 42. Bassett S, Lake B. Use of cold applications in the 25. Cook WA. Antagonistic muscles in the production of management of spasticity; report of three cases. Phys clonus in man. Neurology 1967; 17:779-79. Ther Rev1958; 38:333-34. 26. Hagbarth KE, Wallen G, Lofstedt L. Muscle spin- 43. Knutsson E. Topical cryotherapy in spasticity. Scand dle activity in man during voluntary fast alternating J Rehabil Med 1970; 2:159-63. movements. J Neurol Neurosurg Psychiatry 1975; 44. Hedenberg L. Functional improvement of the spastic 38:625-35. hemiplegic arm after cooling. Scandinavian journal of 27. Cook WA, Jr. Antagonistic muscles in the production rehabilitation medicine 1970; 2:154. of clonus in man. Neurology 1967; 17:779-81. 45. Miglietta O. Action of cold on spasticity. Am J Phys 28. Rossi A, Mazzocchio R, Scarpini C. Clonus in man: Med 1973; 52:198-205. a rhythmic oscillation maintained by a reflex mec- hanism.Electroencephalogr Clin Neurophysiol1990; 75:56-63.

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