No single clinical electrophysiological test can evaluate disorders of muscle tone. These disorders, symptomatic of a variety of diseases have a multifactorial physiological basis. The several tests used are complimentary each aiming to study different aspects of spinal and supraspinal reflexes which become deranged. The H reflex and F wave (H max/M max and F max/M max ratios) measure motoneuron pool excitability in general. The tendon reflex includes spindle mechanisms bypassed by the H reflex and, with limitations, comparison of H max/M max and T max/M max yields information about the -y system. Tonic vibration of a tendon inhibits the H reflex from the same muscle. The TVR measures autogenous presynaptic inhibition exerted by the la afferents of the muscle. Recurrent inhibition via Renshaw cells is evaluated by studying the effect of collision on the H reflex. Reciprocal inhibition of the la afferents can be assessed by measuring H reflex change induced by stimulating la afferents from antagonists. Changes in the H reflex recovery cycle measure polysynaptic influences on spinal motoneuron excitability. Cutaneomuscular (flexor) reflexes measure poly- and oligosynaptic excitatory drive to spinal motoneurons and the blink reflex evaluates the excitatory drive to brainstem motoneurons. Long loop (segmental) responses can be evaluated by limb pertubation using a torque motor or electrical stimulation applied during voluntary muscle contraction. Finally needle electromyography is a more relevant test in several disorders of muscle tone such as the stiff-man syndrome and Isaacs' syndrome.

We have investigated the influence on the excitability of lumbar motoneurons of 5-hydroxytryptamine (5-HT), substance P and thyrotropin releasing hormone (TRH), three substances which coexist in the same bulbospinal descending pathway and end in large part around motoneurons. We have also studied the effect of clonidine, an alpha 2 noradrenergic agonist. This was done in spinalized rats (T5) treated three weeks before with 5-7-dihydroxytryptamine. Under those circumstances 5-HTP (LP.), 5-HT (intrathecally) TRH (LP. or I.T.) and substance P (I.T.) all elicited a strong excitation of motoneurons as measured by integrated EMG of the hindlimb muscles. Substance P reduced by almost half the subsequent response to 5-HTP, 1 hour and 24 hours later. TRH given acutely did not modify the response to 5-HTP but given chronically for twenty one days by means of Alzet minipump, markedly increased the response to 5-HTP. Clonidine by itself decreased the excitability of motoneurons and antagonized the excitatory effect of 5-HTP and TRH. In a pilot trial, cyproheptadine, a 5-HT antagonist was shown to decrease the manifestations of spasticity in patients with a partial spinal lesion. Clonidine also appears to be of potential use in the treatment of spasticity.

The availability of new antispasticity agents has greatly extended the therapeutic arm of the neurologist and has obviated the need for destructive neurosurgical procedures in many instances. Baclofen remains the single most useful agent, but in certain circumstances, benzodiazepines and dantrolene sodium are useful alternative or adjunctive treatments. Tizanidine has been recently introduced, and early experience with this agent appears to be favourable. A variety of new drugs are awaiting further evaluation. The effective use of these agents demands an understanding of their principal mechanisms of action, knowledge of their predictable side effects, and a familiarity with the underlying neurological disorders. The monitoring of clinical efficacy is difficult and is often dependent upon subjective evaluation. The application of electrophysiological studies might facilitate the monitoring of treatment and the prediction of optimum treatment strategies forindividual patients. The use of these pharmacological agents, from the perspective of a clinician, will be discussed.

Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino) -2, 1, 3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks.

A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented.

Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.

MS could well be a two stage disease. The first stage involves the sequential development of multiple small lesions, mostly inflammatory, that accumulate at a given rate. The second stage could be that of consolidation and confluence of lesions that involves not only demyelination but gliosis. MRI now gives us an opportunity to watch the evolution of these processes and also to monitor treatment effects. It is only after the evolution of this process is understood that we can design rational therapies directed toward the prevention of spasticity in MS.

Dystonia is mysterious and its pathophysiology is uncertain. The fundamental motor abnormality is an abnormality of muscle command signals, such that the wrong agonists may be activated for too long, there is abnormal co-contraction of agonist and antagonists, and there is excessive and misdirected action of synergists and postural fixators. The result is action dystonia. In addition, muscle spasms may occur spontaneously. The peripheral motor apparatus, the corticomotoneurone pathway, and (as far as is known) the proprioceptive feedback machinery, are all intact in primary dystonia. However, a defect of interneuronal machinery has been identified in both the brainstem and spinal cord. In blepharospasm there is hyperexcitability of the lower brainstem interneurones responsible for the R2 component of the blink reflex. In the dystonic arm there is loss of the later phases of la reciprocal inhibition from extensors to flexors. Both deficits may be due to loss of normal basal ganglia inputs onto interneurones. The known sites of focal lesions that may cause symptomatic dystonia all impair basal ganglia output. However, whether such abnormal interneuronal function is sufficient to explain dystonia is not known. Among many unanswered questions are 1) are the cortical instructions for movement specified correctly, and 2) what is responsible for the spontaneous dystonic spasms?

A number of pharmacologic agents have been found to be effective for the dystonias. Anticholinergic drugs have been shown to be the most effective in terms of percentage of subjects who receive moderate to marked benefit. About 50% of children and 40% of adults obtain such improvement. Peripheral adverse effects are usually overcome by pyridostigmine. It may be necessary to utilize pilocarpine eyedrops for blurred vision. Central adverse effects, such as forgetfulness, can be reduced only by a reduction in dosage of the anticholinergic. In comparing trihexyphenidyl and ethopropazine, we found that children tend to have better tolerance of the former and adults tend to have better tolerance of the latter. The antidopaminergics are the group of drugs that were found to be the next most effective agents in terms of percentage of patients who respond. However, these drugs, particularly the dopamine receptor blockers, have the capacity to induce tardive dyskinesia and tardive dystonia. Tardive syndromes are difficult to treat and can persist indefinitely. Other agents that have shown usefulness in controlling dystonia are levodopa, baclofen, carbamazepine, and the benzodiazepines, either alone or in combination with each other and with the anticholinergics. Stereotactic thalamotomy is particularly useful in contralateral hemidystonia. The risk of adverse effects is less than with bilateral thalamotomy, which may need to be employed when generalized dystonia is severely disabling and not responsive to pharmacotherapy.