Multiple sclerosis

Multiple sclerosis is characterized by the appearance of disseminated foci of demyelination in the brain and spinal cord.

Characteristic symptoms include visual and oculomotor disturbances, paresthesia, weakness, pelvic dysfunction, and cognitive impairment.

Typically, neurological deficit is multiple, with remissions and exacerbations, gradually leading to disability. The diagnosis of multiple sclerosis is made in the presence of remissions and exacerbations, at least 2 topically separate neurological disorders detected clinically or instrumentally, changes in MRI or other criteria (depending on the complaints). Treatment of multiple sclerosis: glucocorticoids during exacerbations, immunomodulators for the prevention of exacerbations and symptomatic therapy.

Read also: Multiple Sclerosis: Face to Face

Multiple sclerosis is the most common cause of acquired demyelination of the central nervous system, which is essentially an inflammatory process directed against the myelin of the brain and spinal cord. A fairly common disease in the Western Hemisphere and Europe, multiple sclerosis is one of the leading causes of disability in middle-aged and young adults. For most, if not all, patients, multiple sclerosis is a source of significant physical and emotional suffering, and it causes significant economic and social damage to society. In the United States, 300,000 to 400,000 people suffer from multiple sclerosis. Although the exact cause of multiple sclerosis remains unknown and the disease cannot be completely cured, in recent years, drugs have appeared that influence the course of the disease, affecting the pathogenetic processes underlying it, and are able to improve the quality of life and health.

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Epidemiology of multiple sclerosis

Multiple sclerosis (MS) probably involves an immunological mechanism, and it is possible that there is an infection (an unidentified latent virus) that triggers a secondary immune response. Increased prevalence in some families of certain allotypes of the major histocompatibility complex (HLA-DR2) suggests a genetic predisposition. Multiple sclerosis is more common in people who spent the first 15 years of life in temperate climates (1/2000) than in the tropics (1/10,000). Smoking also increases the risk. The onset of the disease is at the age of 15-60 years, typically 20-40 years. Women are more often affected.

Multiple Sclerosis - Epidemiology

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Causes of Multiple Sclerosis

Demyelination areas (called plaques) are revealed, within and around which there is destruction of oligodendroglia, perivascular inflammation, chemical changes in the lipid and protein components of myelin. Axonal damage is also possible, but the cell bodies and axons are fairly intact. Fibrinous gliosis develops in plaques scattered throughout the CNS, first in the white matter, in particular in the lateral and posterior columns (especially in the cervical region), optic nerves and periventricular zones. The conduction pathways of the midbrain, pons and cerebellum are affected. The gray matter of the brain and spinal cord is affected to a lesser extent.

Multiple Sclerosis - Causes and Pathogenesis

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Symptoms of Multiple Sclerosis

Multiple sclerosis is characterized by remissions and exacerbations of neurological deficit. The frequency of exacerbations varies, averaging about 3 times per year. The most common initial symptoms are paresthesias in one or more limbs, the trunk, or one side of the face; weakness or clumsiness in an arm or leg; and visual disturbances (eg, partial loss of vision and pain in one eye due to retrobulbar neuritis, diplopia due to oculomotor palsy, scotomas). Other common early symptoms of multiple sclerosis include numbness or increased fatigability of a limb, gait and pelvic disorders, and dizziness. These signs, indicating mosaic involvement of the central nervous system, may be barely noticeable. Symptoms may worsen with increased temperature (heat, hot bath, fever).

Usually mild cognitive decline, sometimes apathy, decreased criticism and attention, and affective disorders, including emotional lability, euphoria or, more often, depression. Depression may be reactive or develop as a result of brain damage. Epileptic seizures are possible.

Cranial nerves

Unilateral (asymmetric) optic neuritis and bilateral internuclear ophthalmoplegia are typical. Optic neuritis leads to visual impairment (from scotoma to blindness), eye pain, sometimes narrowing of the visual fields, optic disc edema, partial or complete afferent pupillary defect. Internuclear ophthalmoplegia is the result of damage to the medial longitudinal fasciculus, which unites the nuclei of the III and VI pairs of cranial nerves. When looking in the horizontal plane, adduction of one eye decreases and nystagmus of the other appears; convergence is not impaired. Rapid, low-amplitude oscillations of the eye during direct gaze (peduncular nystagmus) are characteristic of multiple sclerosis, but are uncommon. Dizziness is common. Intermittent unilateral facial numbness, pain (resembling trigeminal neuralgia), paralysis, or spasm may occur. Mild dysarthria may occur due to bulbar, cerebellar, or cortical control disorders. Involvement of other cranial nerves is uncommon but may complicate brainstem lesions.

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Motor sphere

Bilateral spastic paresis, predominantly of the lower limbs, usually develops as a result of damage to the corticospinal pathways at the level of the spinal cord. Tendon reflexes (knee and Achilles) are increased, extensor plantar reflexes (Babinski reflex) and clonus of the feet and kneecaps are often detected. Gait disturbances over time may confine the patient to a wheelchair. In the later stages, painful flexor spasm occurs in response to sensory stimuli (e.g., touching bed linen). Brain damage may lead to hemiplegia.

Intention tremor - the limb oscillates during movement - can simulate cerebellar dysmetria (ataxic movements of the limbs). Rest tremor is also encountered, especially noticeable when the head is deprived of additional support.

Cerebellum

In advanced stages of multiple sclerosis, cerebellar ataxia and spasticity lead to permanent disability. Other manifestations of cerebellar damage may include dysarthria, scanned speech (slow pronunciation with hesitation at the beginning of a word or syllable), intention tremor, and nystagmus.

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Sensitivity

Paresthesia and partial loss of sensitivity of any type (e.g., in the arms or legs) are characteristic. Various sensory disturbances (e.g., a burning sensation or pain as if an electric shock were produced) may occur spontaneously or in response to touch, especially in cases of spinal cord damage. An example is Lhermitte's sign, when, when the head is tilted forward, pain like an electric shock radiates from top to bottom along the spine and into the legs. Objective signs of sensory disturbances are transient.

Spinal cord

Spinal cord involvement results in pelvic dysfunction (eg, urgency, urinary retention, or incontinence). Constipation, erectile dysfunction in men, and genital anesthesia in women may occur.

Optic myelitis ( Devic's disease ) is a variant of multiple sclerosis - acute, sometimes bilateral optic neuritis combined with demyelination in the cervical or thoracic spinal cord; leads to vision loss and paraparesis. Another variant is isolated motor weakness due to spinal cord damage without other neurological deficits (progressive myelopathy).

Multiple Sclerosis - Symptoms

Diagnosis of multiple sclerosis

Multiple sclerosis should be suspected in the presence of optic neuritis, internuclear ophthalmoplegia, and other symptoms compatible with multiple sclerosis, especially if the deficit is multifocal or intermittent. Most diagnostic criteria for multiple sclerosis require a history of exacerbations and remissions and objective evidence of two or more focal CNS lesions. MRI of the brain and sometimes the spinal cord is performed. If MRI and clinical findings are inconclusive, additional testing may be needed to objectively demonstrate the presence of lesions. CSF analysis and, if necessary, evoked potentials are usually the first step.

MRI is the most sensitive neuroimaging method. It allows to exclude potentially reversible diseases that mimic multiple sclerosis. Among them are non-demyelinating lesions in the area of the spinal cord-oblongata transition (for example, subarachnoid cysts and tumors in the foramen magnum area). Contrast enhancement with gadolinium helps to differentiate active inflammation from old plaques. Contrast-enhanced CT is an alternative. The sensitivity of MRI and CT can be increased by repeated administration of contrast and delayed scanning.

Usually, the CSF has elevated IgG levels relative to protein (normal <11%), albumin (normal <27%), and other indicators. The IgG level correlates with the severity of the disease. CSF agarose electrophoresis usually reveals a zone of oligoclonal clusters. In the active demyelination phase, myelin basic protein may increase. The lymphocyte and protein levels in the CSF may be elevated.

The method of evoked potentials (latency periods of responses to sensory stimulation) for the diagnosis of multiple sclerosis is often more sensitive than complaints. Visual evoked potentials reveal hidden brain lesions (for example, with confirmed lesions only in the spinal cord). Sometimes somatosensory evoked potentials are assessed, including at the level of the brainstem. Routine blood tests sometimes allow us to exclude, for example, systemic lupus erythematosus, Lyme disease, etc.

Multiple Sclerosis - Diagnosis

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Treatment of multiple sclerosis

The goal of treatment is to reduce the duration of exacerbations, their frequency and the severity of complaints; it is especially important to ensure the ability to walk. In exacerbations that lead to objective deficits (e.g. loss of vision, strength or coordination), short courses of glucocorticoids are prescribed (prednisolone 60-100 mg orally once a day with a decrease in dose over 2-3 weeks, methylprednisolone 500-1000 mg intravenously once a day for 3-5 days). Corticosteroids can shorten the duration of an acute attack, but do not provide a long-term effect. However, methylprednisolone can delay progression in acute severe optic neuritis.

Immunomodulatory therapy reduces the frequency of exacerbations and can delay the threat of disability. Among the immunomodulatory drugs are interferon-beta 1b 8 million IU subcutaneously every other day, interferon-beta 1a 6 million IU intramuscularly weekly. Side effects: flu-like symptoms, depression (decreases over time), the appearance of neutralizing antibodies after months of treatment and cytopenia. Glatiramer acetate 20 mg subcutaneously once a day can be used. Interferon-beta and glatiramer acetate are not immunosuppressants, and in gradually progressive MS, the immunosuppressant mitoxantrone, 12 mg / m ² intravenously every 3 months for a year, can help. Natalizumab is an antibody to alpha ₄ -integrin - inhibits the passage of leukocytes through the blood-brain barrier; with monthly infusions it helps reduce the frequency of exacerbations and the appearance of new lesions, but its approval for the market has been suspended pending the completion of a study of its connection with progressive multifocal leukoencephalopathy. If immunomodulatory therapy is ineffective, monthly intravenous immunoglobulin may help. In severe, progressive multiple sclerosis, immunosuppressants (methotrexate, azathioprine, mycophenolate, cyclophosphamide, cladribine) are used, but the justification for their use remains a matter of debate.

For spasticity, baclofen is given, gradually increasing the dose from 10 to 20 mg orally 3-4 times a day or tizanidine 4-8 mg orally 3 times a day. Gait training and exercise are effective. For neuropathic pain, gabapentin 100-600 mg orally 3 times a day is prescribed, an alternative is tricyclic antidepressants (eg, amitriptyline 25-75 mg orally at bedtime; if amitriptyline causes anticholinergic side effects, then desipramine 25-100 mg orally at bedtime), carbamazepine 200 mg orally 3 times a day, and opioids. For pelvic disorders, treatment depends on their specific mechanism.

Encouragement and support help. Even at advanced stages, regular exercise (exercise bike, treadmill, swimming) is indicated to train the muscles and heart. It reduces spasticity, helps prevent contractures and is psychologically beneficial. Patients should maintain an active lifestyle if possible, but avoid overwork and overheating. Vaccinations do not increase the risk of exacerbation. Weakened patients need prevention of bedsores and urinary tract infections; sometimes intermittent self-catheterization of the bladder is necessary.

• Treatment of exacerbations of multiple sclerosis
• Interferons and Multiple Sclerosis
• Symptomatic treatment of multiple sclerosis

Prognosis for multiple sclerosis

The course of the disease is unpredictable and variable. More often, usually when the disease debuts with optic neuritis, remission can last more than 10 years. In other cases, especially in men who become ill in middle age, there are frequent exacerbations, which leads to disability. Smoking can accelerate the course of the disease. Life expectancy is reduced only in the most severe cases.

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