Symptomatic treatment of multiple sclerosis

This article briefly reviews the most common symptoms of multiple sclerosis and their pharmacological treatment. In patients with multiple sclerosis, pseudo-exacerbations may occur against the background of fever of any origin, which are explained by reversible temperature-dependent changes in the conductivity of demyelinated axons. Methylprednisolone should not be prescribed for untreated infection, since it may be the cause of an increase in symptoms. At the advanced stage of the disease, many patients take a combination of several drugs to relieve symptoms. It is important to remember that the likelihood of side effects (for example, cognitive dysfunction with anticholinergics) increases with the simultaneous use of several drugs, for example, agents for normalizing urinary function, GABAergic antispasmodics, anticonvulsants, and tricyclic antidepressants for the treatment of pain and depression. It is often difficult to decide whether new symptoms, such as fatigue or muscle weakness, are caused by the drugs or the disease itself.

Patients with multiple sclerosis may require general medical care, but they may also require special equipment to accommodate their motor impairment (such as a special examination table). However, patients with multiple sclerosis rarely have contraindications to procedures or medications needed for other conditions. They also do not have contraindications to general or regional anesthesia, pregnancy, childbirth, or immunizations. Careful studies have found no adverse effects of influenza vaccination on the frequency of exacerbations or the rate of disease progression.

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Spasticity

Spasticity occurs as a result of damage to the central motor neurons and the elimination of their inhibitory effect on the segmental apparatus of the spinal cord, through which the reflex arcs are closed. It is usually caused by damage to the descending pyramidal tracts. Damage to the pyramidal tracts is the most common cause of movement disorders in multiple sclerosis. It manifests itself as weakness of the limbs, increased muscle tone, muscle spasms in the upper and especially in the lower limbs. With moderate spasticity, joint movements are difficult. Most often, extension spasms are observed, accompanied by contraction of the quadriceps muscle of the thigh and extension of the lower leg. Flexion spasms with flexion in the knee joint are usually painful and are especially difficult to treat. With severe impairment of movement in the limbs, joint contractures may develop. Spasticity may increase with fever, urinary infection, and in some cases with treatment with INFbeta.

Baclofen. Baclofen is an analogue of gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the spinal cord and brain. Baclofen inhibits both monosynaptic and polysynaptic spinal reflexes and may also have some effect on supraspinal structures. Its dose is mainly limited by the depressant effect on the central nervous system, which may manifest as drowsiness or confusion. The dose of the drug is also limited by other side effects, such as constipation and urinary retention. After oral administration, the concentration of the drug in the blood reaches a peak in 2-3 hours, the half-elimination period is 2.5-4 hours. 70-80% of the drug is excreted in the urine unchanged. Treatment begins with a dose of 5-10 mg at night, and then it is gradually increased, switching to 3-4-time administration. In some cases, the effective dose is 100-120 mg or more. In severe cases, when maximum oral doses do not produce sufficient effect, intrathecal (endolumbar) administration of baclofen is possible using an implanted pump, which allows control of the rate of drug delivery.

Other GABA agonists. Diazepam or clonazepam can be used to enhance the effects of baclofen, especially to reduce nocturnal muscle spasms, although they have a more pronounced CNS depressant effect than baclofen. Clonazepam has the longest duration of action (up to 12 hours) and can be used at a dose of 0.5-1.0 mg 1-2 times per day. Diazepam is prescribed at a dose of 2 and 10 mg up to 3 times per day.

Tizanidine. Tizanidine is an alpha2-adrenergic receptor agonist that acts primarily on polysynaptic (but not monosynaptic) spinal reflexes. After oral administration, serum concentrations of the drug peak after 1.5 hours, and the half-life is 2.5 hours. When taken orally, bioavailability is 40% (due to first-pass metabolism through the liver). Although the hypotensive activity of tizanidine is 10-15 times lower than that of clonipine, it can occur after taking 8 mg of the drug. Due to the possible hepatotoxic effect, it is recommended to study the aminotransferase level 1, 3, 6 months after the start of treatment and then at regular intervals. Tizanidine should be used with caution in the elderly and patients with impaired renal function due to decreased clearance of the drug. Treatment begins with 4 mg, subsequently increasing the dose to 24 mg / day.

Other drugs used to treat spasticity. Dantrolene is indicated for patients with severe spasticity when other drugs have failed. The possibility of severe liver damage and other side effects limits its use in multiple sclerosis. Paroxysmal spasms of the upper and lower extremities may be relieved by anticonvulsants, including carbamazepine, phenytoin, or valproic acid. These drugs may also be effective for other types of paroxysmal symptoms, including pain (eg, trigeminal neuralgia), myoclonus, or dysphonia. Local intramuscular injection of botulinum toxin is also used to treat spasticity in multiple sclerosis.

Pelvic Organ Dysfunction

Dysfunction of urination is one of the most common symptoms in multiple sclerosis. Sometimes severe dysfunction of urination is observed in cases where other manifestations of the disease are mild. Hyperreflexive bladder is characterized by a decrease in functional capacity due to uninhibited contractions of the detrusor. In this case, anticholinergic agents that relax the bladder muscle are effective, for example, oxybutynin, tolteradine or tricyclic antidepressants such as imipramine or amitriptyline. Oxybutynin hydrochloride is prescribed in a dose of 5-10 mg 2-4 times a day, tolteradine - in a dose of 1-2 mg 2 times a day, tricyclic antidepressants are initially used in a dose of 25-50 mg at night, then it is gradually increased until the desired effect is achieved.

Hyoscyamine sulfate is a belladonna alkaloid with cholinolytic activity. It is prescribed at a dose of 0.125 mg every 4 hours. Hyoscyamine is also available in a slow-release dosage form, which is prescribed at 0.375 mg 2 times a day.

An alternative or supplement to anticholinergics may be vasopressin, which also helps with frequent urination. It is used in the form of a nasal spray, which is prescribed once a day - in the evening or in the morning. Propantheline bromide or dicyclomine hydrochloride are also used.

Impaired bladder emptying may result from weak detrusor contractions or from detrusor contractions occurring against the background of a closed external sphincter (detrusor-external sphincter dyssynergia). In detrusor weakness, intermittent catheterization is most effective to prevent accumulation of a large volume of residual urine, but cholinergic drugs such as bethanechol may also be useful. Alpha2-adrenergic receptor antagonists (eg, terazosin and phenoxybenzamine), which relax the sphincter, can be used to treat dyssynergia. Clonidine, an alpha2-adrenergic agonist, may also be used.

Bowel dysfunction may manifest itself as constipation, diarrhea, or urinary incontinence. Anticholinergic drugs used to treat spasticity, urinary disorders, or depression may worsen an existing tendency toward constipation. For constipation, a high-fiber diet and laxatives are recommended.

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Fatigue

The physiological mechanisms of increased fatigue in multiple sclerosis have not been sufficiently studied. In some cases, fatigue is probably associated with high energy expenditure on overcoming spasticity during everyday activities. However, fatigue in multiple sclerosis can be pronounced and can even be the leading symptom in patients with minimal motor impairment and even in those without any motor impairment. Depression should be excluded in patients with multiple sclerosis with loss of strength. Two drugs are most often used to treat pathological fatigue in multiple sclerosis: amantadine, an indirect dopamine receptor agonist, and pemoline, an amphetamine-like drug. Amantadine, prescribed at a dose of 100 mg twice daily, is usually well tolerated, but has only a moderate effect on fatigue. Occasionally, it causes livedo reticularis on the skin. Pemoline is prescribed at a dose of 18.75-37.5 mg once daily. Due to the possibility of tachyphylaxis in relation to the anti-asthenic effect of pemoline, it is recommended to take breaks in taking the drug for 1-2 days per week.

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Pain

Pain sometimes occurs in patients with spinal cord damage. It is usually localized in the same way as the sensory disturbances and is described by patients as burning, resembling paresthesia, or, conversely, as deep. Tricyclic antidepressants and anticonvulsants are used to reduce pain, including drugs with GABA-ergic action - gabapentin, diazepam or clonazepam. Baclofen may also be useful in these cases.