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May 2005, Volume 55, Issue 5

Original Article

Eperisone compared to Physiotherapy on Muscular Tone of Stroke Patiehts: a Prospective Randomized open Study

Mohammad Tariq  ( Department of Neurology, Pakistan Institute of Medical Sciences(PIMS), Islamabad )
Nasim Akhtar  ( Department of Neurology, Pakistan Institute of Medical Sciences(PIMS), Islamabad )
Mohammad Ali  ( Department of Neurology, Pakistan Institute of Medical Sciences(PIMS), Islamabad )
Sohail Rao  ( Department of Neurology, Pakistan Institute of Medical Sciences(PIMS), Islamabad )
Mazhar Badshah  ( Department of Neurology, Pakistan Institute of Medical Sciences(PIMS), Islamabad )
Mohammad Irshad  ( Department of Neurology, Pakistan Institute of Medical Sciences(PIMS), Islamabad )


Objectives: To compare the effects of Eperisone, a muscle relaxant and physiotherapy on the muscular tone after stroke.

Twenty six (26) patients were included from age 15 to 75 years in an open prospective randomized study of three weeks duration and were treated with either Eperisone (n=13) or were advised to undergo formal physiotherapy (n=13) at the department of physiotherapy PIMS. The end point was observed in the form of change in the grade of tone. Safety and tolerability was assessed on the basis of adverse events.

Results: Eperisone was found to be comparable to physiotherapy in reducing the spasticity in patients
after stroke and improved the grade of tone from 3-2 (n=2), 4-3 (n=2), 2-1(n=2). The safety analysis showed persistent vomiting (n=1), fatigue (n=1), headache and dry mouth (n=2), epigastric pain (n=1) and slight changes in blood pressure under Eperisone which was generally well tolerated by the patients.

Conclusion: Eperisone was found to be comparable to physiotherapy in its effects to improve spasticity in patients after stroke(p>0.05) (JPMA 55:202;2005).


Several cerebrovascular diseases, spastic spinal paralysis, cervical spondylosis, amyotrophic lateral sclerosis, spinocerebellar degeneration and other spinal vascular diseases are accompanied by spasticity. Spasticity is believed to arise from the release of sustained inhibition from the higher central nervous system. Although a certain degree of tone in stroke patients is necessary for maintenance of the body posture but excessive tone results in marked interference in daily activities of life. Several central muscle relaxants have recently been developed to treat various diseases with spasm as a chief complaint. These drugs mainly act at polysynaptic reflex mechanism to improve the spasm as demonstrated in experimental models.

These drugs reduce spasticity; improve reflexes, walking capabilities and subjective symptoms of spastic paralysis.1,2 In the background of many trials the present trial was conducted to investigate the therapeutic effects and safety profile of the drug in stroke patients at PIMS (Pakistan Institute of Medical Sciences) Islamabad.

Patients and Methods

Study design

It was a prospective randomized open study. Informed consent was taken from all the participants. The duration of the study was 3 weeks. Alternate patients with stroke and hemiplegia attending Neurology OPD were selected. The patients were advised to take either Eperisone Hcl three tablets a day or referred for formal physiotherapy at department of Physiotherapy PIMS. These patients were offered passive with active exercises depending on the initial grade of the power, for one hour daily for 3 weeks.

Twenty-one day supply of medicines was given. On return visit they were questioned on the intake of medicines to determine compliance. Physiotherapy card was checked to assess the attendance in physiotherapy sessions. Only those patients who were regular with medicines and physiotherapy sessions were included in the study.

The patients were examined at visit 1(trial entry examination) their name, age, sex, address and baseline blood pressure was recorded. Brief medical history, treatment for hypertension in the past one month, any concomitant disease and medication if any, was documented. Neurological examination was conducted by assessing the tone, power, reflexes, Babinsiki's sign and range of movement power of both upper and lower limbs.

Tone was assessed by the following grade:

In upper limbs tone was assessed as: 0) Hypotonia, 1) Normal tone, 2) Slightly increased tone (Pronator catch), 3) Moderately increased tone (increased resistance on movement but no clasp knife rigidity) and 4) Severely increased tone (clasp knife rigidity).

In lower limbs tone was graded as: 0) Hypotonia, 1) Normal tone, 2) Slightly increased tone (Flexion around the knee also lifts the heel), 3) Moderately increased tone (increased resistance on movement but no clasp knife rigidity) and 4) Severely increased tone (clasp knife rigidity).

Power was assessed by the following grades: 0) No movement, 1) Flicker of contraction, 2) Horizontal movement eliminating the effect of gravity, 3) Movement against the gravity but not against the resistance, 4) Against the gravity and also against the resistance but not the normal full power and 5) Normal power.

Range of movement was determined as: 1) No movement, 2) Severely impaired, 3) Slightly impaired and 4) Full movement. Patients were re-examined at second visit after 3 weeks.

Adverse events were recorded if any according to the grades: 1) Mild: Does not interfere with the routine activities, 2) Moderate: Interferes with the routine activities and 3) Severe: Impossible to perform routine activities.

Inclusion criteria were: Patients age above 15 and below 75 years, patients suffering from mild/moderate HTN and Features of CVA for the last one month.
The exclusion criteria comprised of seriously ill patients, patients suffering from hepatic or renal impairment and pregnant/lactating women.


There were 26 patients who participated in the study of whom 13 received medication and 13 were offered formal physiotherapy. Only 17 patients came for a second visit of whom 8 were on Eperisone. Three of these cases had right-sided hemiplegia and 5 had left sided hemiplegia. From these 8 patients 6 showed improvement in muscle tone with the grade changing from 3-2 (n=2), 4-3 (n=2) and 2-1 (n=2). Two patients in treatment group did not show any change.

Of the 13 patients on physiotherapy, only 9 had a revisit. Of these 9 patients 7 had right sided whereas 2 had left sided hemiplegia. In this group 4 patients improved showing a change in tone. Two patients improved from grade 3 to 2 whereas 2 from grade 2 to 1. Of the Eperisone group, 6 (75%) showed improvement in spasticity whereas in the physiotherapy group 4 (44%) improved.

Regarding side effects, one patient discontinued treatment because of persistent vomiting. Two of the 8 cases who re-visited experienced dryness of mouth(25%). One had epigastric pain (12.5%), one had headache (12.5%) and one had fatigue (12.5%). Overall the drug was well tolerated.

Among the patients receiving treatment with Epirisone, 3 patients showed slight increase in the systolic BP.Among the physiotherapy group there were 6 patients who had high BP as compared to base line BP measurement.


The oral medications that are most commonly used for spasticity are diazepam, dantrolene, oral baclofen and tizanidine, which is a relatively new medication. Benzodiazepines reduce muscle tone and painful spasms by increasing the affinity of GABA receptors for endogenous GABA, predominantly at the spinal cord level3, but it causes habituation and tachyphylaxis and more so causes sedation and confusion.4 Dantrolene acts on skeletal muscles to reduce muscular tone by directly interfering with excitation-contraction coupling reaction.5 It is also of limited use because it is hepatotoxic and also causes muscular weakness.4

Baclofen is -aminobutyric acid (GABA) agonist and acts by inhibiting both monosynaptic and polysynaptic spinal cord reflexes.6 The drug however is poorly tolerated because of sedation, mental confusion and by causing muscular weakness.4,7,8 The intrathecal baclofen, or ITB therapy, is a relatively new treatment, which has had a dramatic effect on the lives of my patients with generalized spasticity.9

Tizanidine is an imidazoline derivative which acts at a2-receptors in the brain and spinal cord by decreasing the excitability of a and d motor neurons in the spinal cord by reducing the release of excitatory neurotransmitters in the spinal cord and decreasing the action of these excitatory neurotransmitters at their receptors.10

For focal spasticity Botulinum toxin A in injectable form has been successfully used in the recent past which acts by inhibiting the neuronal release of acetylcholine, producing functional denervation of muscle fibers4 and reduces spasticity.

Our study shows that Eperisone is a useful drug for treatment of muscular hypertonic symptoms in patients with stroke. Three tablets of Eperisone can be used in three divided doses after each meal and can be adjusted according to patient's age and symptoms. It reduces skeletal muscular spasticity via its actions within the CNS and relaxes vascularsmooth muscle directly. It primarily acts at the spinal cord level and gamma motor neurons therefore it suppresses spinal reflexes and reduces the sensitivity of muscle spindles, also enhances blood circulation and has analgesic effects.

One of the reports by Ohtomo et al. mainly in patients with cerebrovascular disturbance,11 muscular stiffness in resting and walking conditions and difficulty in walking showed remarkable improvement with use of Eperisone.

An overall improvement in tone in 33% of the patients on 150 mg/day dose and 78% of patients on 300 mg /day was reported by Yoshigoro et al.12 Kiyokata et al observed the effects of Eperisone on patients with headache caused by muscular tension. Improvement was had in 70% of patients on 150mg daily after one week. Continuous administration in 300mg daily dose had better effects on tension headache.13

The present study showed that Eperisone is an effective drug for reducing spasticity after stroke, has very few side effects a good safety profile and tolerability. It has slightly beter effects when compared to physiotherapy alone, although the change in tone was only of one grade. Our study did not check the functional improvement in the patient's condition. Moreover, the small number of patients and a large drop off rate limits this study.

High drop off rates in both arms of the study indicate, that patients probably did not take medicine regularly and attend physiotherapy sessions. The study outcome measures were non-blinded and sample size was too small to detect a statistically significant difference. A larger study may be more conclusive.


Eperisone was provided free of cost by the manufacturers for the study patients.


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11. Ohtomo E. Clinical effects of E-0646 on contracture and spasmodic paralysis. Control study with placebo. Medical consultation and new remedies 1982;19:2073-96.

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13. Nishikata K, Shimomura T, Takahashi K. Clinical examination of eperisone hydrochloride (Myonal) on headache caused by muscle tension. Med Consult N Remedy 1985;22:1-20.

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