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Symptomatic Treatment of Multiple Sclerosis

Treatment of Spasticity, Weakness, Fatigue, Pain and Bladder Dysfunction in Multiple Sclerosis

Symptomatic Treatment of Multiple Sclerosis

Symptomatic treatment does not address the cause of multiple sclerosis. It is not intended to prevent relapses or future disability. Symptoms of MS significantly affect quality of life.

The goal of symptomatic treatment is improvement of the quality of life by reducing some of the MS symptoms.

Spasticity Treatment in Multiple Sclerosis

Spasticity is an increased muscle tone produced by the brain and the spinal cord lesions. Muscle tone is usually higher in the antigravity muscles (flexors in the upper limbs and extensors in the lower limbs) in strokes and other brain disorders. In MS this difference is sometimes not so obvious.

Spasticity does not come independently of weakness, but it does cause some additional problems. Spasticity has an important role in ability to hold the body weight; it is actually rather beneficial. In paralysis caused by peripheral nerve damage muscles are flaccid and are unable to resist the gravity force and hold the body upright. Increased tone in the leg extensors allows staying upright even with minimally preserved voluntary control over the muscle function.

This body defensive mechanism comes at a price. Constantly unbalanced muscle pull generates contractures (permanent muscle stiffness), painful muscle cramps, and causes additional problems with ambulation.

Strength in the limbs might be sufficient for the intended task, but the stiffness decreases the speed and accuracy of movements.
Another problem is painful muscle spasms. Antagonist muscles (the ones that pull the joint in opposite directions) may contract at the same time. This is a very disturbing experience.

Due to MS plaques location preferences (spinal cord and around the ventricles) spasticity in the legs is usually significantly worse than in the arms.

Spasticity management is tricky. The goal is to decrease the abnormal muscle tone without causing significant weakness. In mild spasticity stretching exercises might be a sufficient measure.

Baclofen (Lioresal) is the most commonly used medication for muscle spasms and associated pain. The dose varies greatly depending on individual response (from 10mg to 160 mg per day). Initially low dose is gradually increased until desired effect is reached.
Baclofen may cause weakness and worsen ability to walk. It causes sedation. Baclofen dose is titrated in order to reach spasticity control without producing significant weakness and sedation.
Baclofen, especially in high doses, should not be stopped abruptly. Withdrawal symptoms might be severe. Seizures and mental status changes are the main concerns.
Intathecal baclofen pump may be offered to patients who are unable to walk, cannot tolerate adequate oral dose, or have severe spasticity especially in the legs.

Tizanidine (Zanaflex) has a different mechanism of action. It has similar side effects of sedation and weakness. The difference is that sedation is more pronounced than in Baclofen, but it produces less weakness.
Usual dose is between 4 mg and 36 mg per day. The starting dose is usually 1mg to 2 mg per day. It is started while the patient is on Baclofen. Depending on the response to Tizanidine, Baclofen can be partially and then completely gradually discontinued.

Diazepam (Valium) has similar to Baclofen mechanism of action, side effects, and it has a significant dependence potential. Its use in spasticity management is limited.

Gabapentin (Neurontin) offers only mild benefit in spasticity management.

Dantrolene (Dantrium) acts directly on the muscles and produces muscle relaxation. It is very effective in spasticity, but its use is limited by the side effects – mostly liver toxicity.

Weakness treatment in MS

Muscle weakness is one of the most common symptoms in MS. It is the major cause of difficulty ambulating and disability.

Dalfampridine-SR (Ampyra)

Ampyra acts directly on nerve fibers with damaged myelin by improving conduction. It is proven in clinical trials that Ampyra increases walking speed in MS patients.

Heat sensitivity with worsening symptoms is common in MS (Uhthoff phenomenon). Ampyra alleviates this sensitivity as well.
Clinical trials demonstrated that it subjectively improves spasticity, weakness, sensory symptoms, and speech problems.

Most common dose dependent side effects are tingling, stomachache, dizziness, nausea, and vomiting. The major concern is lowering of seizure threshold which may cause seizures in non-epileptic patients. It is contraindicated in epilepsy. Seizures while in therapy necessitate discontinuation of the drug.

Suboptimal kidney function leads to delayed elimination of the drug and increases toxicity, which requires lower dose.
This medication is contraindicated in moderate-to-severe renal insufficiency.

Sensory Symptoms Treatment in MS
Loss of sensation cannot be treated. Unpleasant sensations such as tingling, burning (neuropathic pain) is usually treated with Gabapentin (Neurontin), Pregabaline (Lyrica), Carbamazepine (Tegretol), and antidepressants – Duloxetine (Cymbalta), Amitriptyline (Elavil), Nortriptyline (Pamelor).
MS Paroxysmal Symptoms Treatment

Trigeminal neuralgia affects 2% of MS patients. Sometimes it involves both sides. Trigeminal neuralgia in MS responds to the same medications as trigeminal neuralgia due to any other cause. Carbamazepine (Tegretol) is the most effective drug.

Paroxysmal tonic spasms respond well to Carbamazepine and Oxcarbazepine (Trileptal).

Fatigue Treatment in Multiple Sclerosis

Fatigue is extremely common in MS. As much as 80% reports fatigue sufficient to affect daily activities. Fatigue is reported as the most disabling symptom by 40%.

Amantadine (Symmetrel) 100 mg twice a day has been shown to improve fatigue in 30% of patients. It is overall a benign drug, which is OK for prolonged use. It has no addiction potential. Common issues are hallucinations, nausea, stomach upset, hyperactivity, and difficulty falling and staying asleep.

Aspirin 650 mg twice a day offers benefit according to one study.

Wake promoting agents Modafinil (Provigil), Armodafinil (Nuvigil) and stimulants Methylphenidate (Ritalin), Adderall are frequently used, but their benefit remains controversial.

Bladder Problems Treatment in Multiple Sclerosis

The most common bladder related initial symptom in MS is urinary urgency. It is caused by premature contraction of the bladder, which prevents it from storing an adequate volume of urine.
It is one of the first symptoms in 15% of MS patients and more than 50% will eventually develop bladder dysfunction. It is caused by spinal cord and periventricular lesions and correlates with lower limbs weakness.

There are multiple drugs on the market, which act by relaxing the bladder (detrusor) muscle. They are called anticholinergic drugs: Oxybutynin (Ditropan), Propantheline (Pro-Banthine), Solifenacin Succinate (Vesicare), and others.
Their typical side effects are drowsiness, dry mouth, and constipation. High doses may cause urine retention (inability to urinate and bladder distension as a result). This is a potentially dangerous complication and it has to be watched for.

Later in the disease the problem might be opposite. The bladder muscle may lose the tone leading to difficulty urinating. Medications with opposite effect, or cholinergic, (such as Bethanechol) become useful. They increase the bladder muscle tone and help with urination. Medication effect is usually suboptimal, which requires chronic intermittent catheterization – catheter is placed on as needed basis.

The hardest to manage is so called sphincter-detrusor dyssynergia. The muscle in the bladder wall, detrusor, contracts. The sphincter, which controls the opening, fails to relax. Using combination of different drugs may be helpful but usually fails. It is commonly treated by combination of medications (anticholinergic) and catheterization.

Considering frequent UTIs, urine acidification by drinking cranberry juice or taking vitamin C (1000 mg per day) is usually recommended.

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