Medullary Actions An

Electrophysiological Study

Marc

Bratzlavsky, MD,

polysynaptic pathways. Proprioceptive re-

flexes behaved variably. The observations are discussed in regard to the possible sources of enhanced motoneuronal activity in tetanus. It is concluded that, besides depression of inhibitory synapses on motoneurons, interneuronal damage may contribute to the tetanus symptomatol-

(Arch

Neurol

in Man

Henri vander Eecken, MD

\s=b\ Brain-stem reflexes have been studied in four patients with generalized tetanus. Inhibitory cutaneous reflexes were abolished or severely depressed. The same held true, to a lesser degree, for excitatory cutaneous reflexes with long

ogy.

of Tetanus Toxin

33:783-785, 1976)

impedance head with an aecelerometer preamplifier and measuring amplifier. Electrical stimuli were applied with a bipolar skin electrode (interelectrode dis¬ tance, 2 cm). A constant current stimulator was used, delivering rectangular shocks of

Electrophysi al investigations studyingologicmedullary

actions the of tetanus toxin in cats1"1 have stressed depression of synaptic inhibi¬ tion as the source of tetanic motoneuron hyperexcitability. Struppler et al' confirmed this finding in man by showing a reduction of inhibitory reflexes in cases of localized and generalized tetanus. The present work further analyzes the possible sources of enhanced motoneuronal activity in tetanus patients by studying inhibito¬ ry as well as excitatory reflexes in the cranial musculature.

0.5

Ten normal control subjects of either sex and four men with generalized tetanus have been studied. During examination, the subjects reclined in bed. Mechanical stimuli were delivered by means of an electrodynamic type force generator to which an impedance head was attached (linear displacement, 1 to 3 mm; circular contact surface, 1.5 cm in diameter). The duration of the mechanical stimuli was 5 msec. Their intensity was adjustable from 0.01 newton to 10 newton, with steps of 0.01 newton. It was assessed by connecting the

were

Department of Neurology, University of Ghent (Belgium). Reprint requests to Department of Neurology, Academisch Ziekenhuis, De Pintelaan 135, B-9000 Gent, Belgium (Dr Bratzlavsky).

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studied:

(1) The myotatic masseter reflex;' or jaw jerk, was elicited by a downward tap to the chin. The recording electrodes were located over the masseter muscle, the reference electrode being placed at the level of the

1976.

From the

in duration and 1 to 15 mamp in

eous silver disk electrodes (0.7 cm in diameter) placed 3 cm apart. After ampli¬ fication, the muscular responses were displayed on the cathode ray oscilloscope of an electromyographic apparatus and filmed on direct print paper. In each subject, five brain-stem reflexes

SUBJECTS AND METHODS

Accepted for publication April 26,

msec

intensity at a frequency always kept below one cycle per three seconds. Reflex responses were picked up from the masseter, orbicularis oris, and orbicularis oculi muscles by means of two cutan¬

-

muscle tendon. (2) The proprioceptive masseteric silent period?'' was studied after inducing on a background of spontaneous or voluntary electromyographic (EMG) activity a twitch contraction of the masseter muscle, either by myotatic reflex activation or by direct electrical muscle stimulation. (3) The crossed exteroceptive masseter inhibition'""1 was obtained on a back¬ ground of spontaneous or voluntary EMG activity by electrical stimulation of the ipsilateral or contralateral labial mucosa. (4) The lip-tap reflex'" was induced in

the orbicularis oris muscle by applying single, short mechanical pulses to the lips. The recording electrodes were placed over the orbicularis oris muscle near the corner of the mouth. (5) The short- and long-latency blink reflex components1"1-' were analyzed after delivering single electrical pulses to the supraorbital skin. The recording electrodes were placed over the orbicularis oculi muscle at the level of the inferior eyelid

Reflex Jaw jerk Silent period masseter

performed. It has been reported previously that the normal human jaw jerk occurs after a latency of approximately 7 msec, and has a central relay time that strongly suggests a monosynaptic re¬ flex.'' In the present study, the jaw jerk was recorded as a biphasic summation potential whose peak-topeak amplitude varied from 0.2 to 2.5 mV. Its threshold ranged from 0.7 to 1 was

newton chin

tap intensity. The masseteric silent period had a duration of

depending on the strength of the foregoing contraction. It was elicited by a threshold electrical stimulus of 5 to 7 mamp, just suffi¬ 20 to 100 msec,

cient to induce a brief contraction of the masseter muscle. The exteroceptive suppression of voluntary masse¬ ter activity is known to contain an early and a late component (R, and R,

inhibitory masseter, respectively), whose respective latencies are in the

range of 10 to 15 msec and 30 to 60 msec, respectively.""11" On electrical stimulation of the labial mucosa in the control subjects, their threshold inten¬ sity varied from 3 to 4 mamp, being often slightly lower for the early

component. The tap-induced lip reflex also contains

an

early

and

a

late

component.1' The reflex is difficult to elicit at rest, and is more prominent when evoked

on a background of slight voluntary activity.11 In the control subjects, both lip reflex compo¬ nents (R, and R., lip-tap) were induced at much the same threshold intensity

+

masseter

RESULTS Control Subjects

analysis

+

Inhibitory

++

R,t R,.t Lip-tap R,

-

+t

R, Blink

+

+4 +

-

R, R_,

+T

+T +

+

-

+

+1+1

+

+

+|

+

+indicates normal; +4 .potentiated: +f depressed; and —, abolished. t/R, indicates early component; R2, late *

,

component.

(0.2

to 0.3

newton) and had

an

The subse¬

quent silent period was brief (about 20 msec duration). When evoked by direct stimulation of the masseter muscle, it

Patient*

margin.

The ten normal subjects were between 22 and 60 years old. Control values for the several tested brainstem reflexes were obtained for the reflex threshold and on the reflex amplitude or duration. No statistical

peak amplitude of about 6 mV.

Brain Stem Reflexes in Four Patients With Generalized Tetanus

ampli¬

ranging between 0.2 and 2 mV. early and the late blink-reflex components (R, and R, blink) showed an amplitude of between 0.2 and 1.5 mV. They were elicited at approxi¬ mately the same threshold intensity (3 to 5 mamp).

tude The

reached 40 msec in duration. The early and the late exteroceptive masseter inhibitions were abolished bilaterally. The early liptap reflex component was facilitated, being induced by taps of 0.1 newton in intensity and reaching an amplitude of 4 mV on stronger tapping. It was often followed by a transient pause in the orbicu¬ laris oris activity, lasting 10 to 20 msec. The late lip-tap reflex component was abol¬ ished. The two blink reflex components showed a marked difference in threshold: the early component had a low threshold (3 mamp) while the late component was elic¬ ited at a threshold intensity of about 10 mamp. The maximal amplitude was 2 mV for the early and 0.4 mV for the late

component.

Case 2.—A 48-year-old man was exam¬ ined on the tenth day of tetanus. The jaw jerk was normal and followed by a silent period lasting 30 to 50 msec. Direct elec¬ trical stimulation of the masseter muscle evoked a silent period of 60 msec. The

short-latency exteroceptive

masseter inhi¬

man was exam¬

bition had an increased threshold intensity of 8 mamp. The long-latency exteroceptive masseter inhibition was abolished, as was the late lip-tap reflex component. By contrast, the early lip-tap reflex compo¬ nent was easily evoked on the background of spontaneous tonic orbicularis oris activ¬ ity, by taps of 0.2 newton. It reached an amplitude of 2 mV. The first blink reflex component was normal, but often followed by a short pause of 10 to 15 msec in the spontaneous orbicularis oculi activity. The second blink reflex component had an increase in threshold, requiring a stimula¬ tion intensity at or above 9 mamp. Its amplitude remained within normal limits. Case 3.—A 59-year-old man was exam¬ ined on the ninth day of tetanus. The jaw jerk was potentiated, exhibiting a maximal amplitude of 5.5 mV, with a threshold of 0.6 newton. No subsequent silent period was observed. On electrical stimulation of the masseter muscle, the silent period never lasted more than 30 msec. Both the shortand the long-latency exteroceptive masse¬ ter inhibitions were abolished. The lip-tap reflex and the blink reflex components behaved similarly: their early component was potentiated, reaching amplitudes of 3 to 4 mV, while their late component re¬ mained within physiological limits. The reflex thresholds were normal.

the seventh day of tetanus symp¬ toms. The jaw jerk was hyperactive. It was elicitable by light chin taps of 0.5 newton intensity and had a maximum peak-to-

Case 4.—A 53-year-old man was exam¬ ined on the 12th day of tetanus. The jaw jerk and the masseter silent period were normal. The short- and long-latency exter-

Patients

The four tetanus patients were conscious during examination. They had typical histories and symptoms, with trismus and severe rigidity in the extremity muscles. Case 1 also had marked hypertonia of the facial mus¬ cles, causing narrowing of the pal¬ pebrai fissure and mild retraction of the corner of the mouth. In all the pa¬ tients, the EMG examination of the masseter, orbicularis oris, and orbicu¬ laris oculi muscles revealed a sponta¬ neous tonic activity of motor units pulsating at frequencies of between 10 and 40 cps. Three patients recov¬ ered after treatment. One (case 1) died from pneumonia. In each tetanus patient, the threshold, amplitude, and duration of the different investigated brain stem reflexes were analyzed and compared with the control values. The results are summarized in the Table. Case 1.—A

ined

26-year-old

on

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oceptive

masseter inhibitions were abol¬ ished. The early lip-tap reflex was facili¬ tated: it was elicited at a threshold inten¬ sity of 0.2 newton and showed a maximal amplitude of 4.5 mV. The late lip-tap reflex was obtained at an increased threshold intensity of 0.8 newton, and had a low amplitude of about 0.5 mV. The early blink reflex component was normal, while the late blink reflex component had an in¬ creased threshold of 7 mamp.

COMMENT In experimental animals, at least three actions have been attributed to tetanus toxin at the medullary level: (1) depression of inhibitory synapses on motoneurons,11 (2) destruction of interneurons,"1 and (3) damage to motoneurons.17 Although all these effects could theoretically produce motoneuronal hyperexcitability, disinhibition is most commonly accepted as the source of tetanic rigidity. The present observations are in agree¬ ment with this conclusion, confirming

former EMG studies in man.1 Both short- and long-latency inhibitory cutaneous reflexes in jaw-closing musculature were abolished or se¬ verely depressed in the tested pa¬ tients. The results suggest, however, that, at least at the bulbar level, a disturbance in synaptic inhibition is not the sole factor involved in tetanus. Indeed, irrespective of their excita¬ tory or inhibitory character, all late exteroceptive cranial reflex compo¬ nents were usually depressed, while short-latency excitatory reflexes were mostly enhanced. While the latter finding can be explained by the motoneuron hyperexcitability, the se¬ lective impairment of reflexes with

long polysynaptic pathways supports the assumption of interneuronal dys¬ function; interneuronal damage is well known as a cause of rigidity.1" Contrasting with the exteroceptive inhibitory reflexes, the proprioceptive masseteric silent period was never

abolished in the tetanus patients. This likely results from its partial genera¬ tion by motoneuronal disfacilitation.8 In two patients, the jaw jerk and the proprioceptive masseteric silent peri¬ od were normal. Two other patients had a marked potentiation of the jaw jerk, which coincided with a depres¬ sion of the silent period. Instead of resulting from defective inhibitory synapses on a-motoneurons, the latter could be related to -motoneuron hyperactivity. If so, the behavior of proprioceptive reflexes in tetanus pa¬ tients would depend on whether moto¬ neuronal hyperexcitability is re¬ stricted to the alpha pool or involves both the alpha and the gamma pool. This could be an important factor in determining the severity of tetanic

rigidity.

This investigation was supported by a grant from the Belgian "Nationaal Fonds voor Wetenschappelijk Onderzoek."

References 1. Brooks VB, Curtis DR, Eccles JC: The action of tetanus toxin on the inhibition of motoneurones. J Physiol 135:655-672, 1957. 2. Curtis DR: Pharmacological investigations upon inhibition of spinal motoneurones. J Physiol 145:175-192, 1959. 3. Wilson VJ, Diecke FP, Talbot WH: Action of tetanus toxin on conditioning of spinal motoneurons. J Neurophysiol 23:659-666, 1960. 4. Struppler A, Struppler E, Adams RD: Local tetanus in man. Arch Neurol 8:162-178, 1963. 5. McIntyre AK, Robinson RG: Pathway for the jaw jerk in man. Brain 82:468-474, 1959. 6. Bratzlavsky M: Pauses in activity of human jaw closing muscle. Exp Neural 36:160-165, 1972. 7. Hufschmidt HJ, Spuler H: Mono- and polysynaptic reflexes of the trigeminal muscles in human beings. J Neurol Neurosurg Psychiatry

25:332-335, 1962. 8. Hoffmann P, Tonnies JF: Nachweis des v\l=o"\lligkonstanten Vorkommens des Zungen\x=req-\ Kieferreflexes beim Menschen. Pfluegers Arch 250:103-108, 1948. 9. Yu SKJ, Schmidt A, Sessle BJ: Inhibitory effects on jaw muscle and activity of innocuous and noxious stimulation of facial and intraoral sites in man. Arch Oral Biol 18:861-870, 1973. 10. Kugelberg E: Facial reflexes. Brain 75:385\x=req-\ 396, 1952. 11. Rushworth G: Observations on blink reflexes. J Neurol Neurosurg Psychiatry 25:93\x=req-\ 108, 1962. 12. Shahani BT, Young RR: Human orbicularis oculi reflexes. Neurology 22:149-154, 1972. 13. Bratzlavsky M: Inhibitory interactions between Group Ia masseter afferents and labial

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mechanosensitive input in man. Brain Res 96:124-127, 1975. 14. Bratzlavsky M: Human brainstem reflexes, in Shahani M (ed): The Motor System: Neurophysiology and Muscle Mechanisms. Amsterdam, Elsevier Publishing Co, 1975, pp 135-154. 15. Ekbom KA, Jernelius B, Kugelberg E: Perioral reflexes. Neurology 2:103-111, 1952. 16. Foster JB, Matzke HA: Neurocytology of experimental ascending tetanus. World Neurol 2:22-35, 1961. 17. Tarlov IM: Rigidity and primary motodamage in tetanus. Exp Neurol 44:246\x=req-\ 254, 1974. 18. Gelfan S, Tarlov IM: Interneurones and rigidity of spinal origin. J Physiol 146:594-617, 1959. neuron

Medullary actions of tetanus toxin. An electrophysiological study in man.

Medullary Actions An Electrophysiological Study Marc Bratzlavsky, MD, polysynaptic pathways. Proprioceptive re- flexes behaved variably. The obse...
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