NEUROLOGY AND NEUROSURGERY - Y. V. ALEKSEYENKO - 2014

MULTIPLE SCLEROSIS. ACUTE DISSEMINATED ENCEPHALOMYELITIS

Demyelinating diseases of The Nervous system include multiple sclerosis, ACUTE DISSEMINATED ENCEPHALOMYELITIS, and several other rarer nosological entities. What unites this group of disorders is the underlying mechanism of demyelinating Brain damage involving the destruction of the myelin sheaths of nerve fibers, which leads to impaired Nerve Impulse Conduction and The Emergence of diverse neurological syndromes.

Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the nervous system characterized by multifocal, wave-like damage predominantly affecting the White matter OF the BRAIN AND SPINAL cord. One of the defining features of this nosological entity is the multifocal Nature of the nervous system involvement. This characteristic is more accurately captured by the English synonym—multiple sclerosis—widely used in international literature. The second defining feature of this pathology is the relapsing-remitting course of the pathological process and the clinical manifestations of the disease.

MS is a condition that most commonly affects young adults, although it can also develop in children. Women are affected 2 to 3 times more frequently than men. The risk of developing MS is determined to some extent by the geographical region of residence prior to Puberty. The prevalence of MS in various geographical zones increases with distance from the equator. A high risk of MS (approximately 50 cases per 100,000 population) is observed in Northern and Central Europe, Canada, the northern United States, southern Australia, and New Zealand. The disease is relatively rare in Africa, as well as in the Near and Middle East.

Etiology, Pathogenesis, and Pathomorphology of Multiple Sclerosis

Currently, MS is viewed as a multifactorial disease whose development stems from the interplay of environmental and genetic factors. The Significance of genetic predisposition to MS is supported by the existence of familial cases. It is well established that the risk of developing MS is significantly higher in the families of patients. This hereditary predisposition is determined by specific individual immune system response traits associated with human leukocyte Antigens (HLA) on chromosome 6, as well as genes governing The properties of myelin Proteins, nonspecific Enzymes, and cytokine activity involved in the chronic demyelinating process. Thus, the genetic predisposition to MS is polygenic in nature. Among external or environmental factors, viral infections, trauma, psycho-emotional stress, physical fatigue, intoxications, and other triggers capable of disrupting Homeostasis and initiating inflammatory and autoimmune mechanisms of CNS damage are likely of primary significance.

The core pathogenesis of MS involves an immunopathological process engaging microglia, astrocytes, and vascular endothelium, which leads to demyelination—namely, the destruction of the myelin sheaths of nerve fibers and, consequently, axonal degeneration and impaired nerve impulse conduction. The morphological substrate of this pathology is The formation of numerous demyelinating lesions accompanied by perivascular infiltration of brain tissue with lymphoid elements and local edema, culminating in areas of sclerosis or gliosis. This explains the Water/144.html">Origin of the term multiple sclerosis (MS).

Demyelinating plaques can occur in virtually all PARTS OF THE nervous system. However, the most characteristic areas of involvement are the periventricular white matter of the cerebrum, the lateral and posterior columns of the cervical and thoracic Spinal Cord, the Cerebellum, the Brainstem, and the visual system. Consequently, phylogenetically younger structures that are most vulnerable to exogenous factors and homeostatic fluctuations are affected first.

Clinical Manifestations of Multiple Sclerosis

The clinical manifestations of MS are determined by the localization of demyelinating lesions within the nervous system. Topically, they can be grouped into several primary categories:

   1. visual disturbances - decreased visual acuity or blurred image perception, and the appearance of scotomas due to involvement of The Optical System (retrobulbar neuritis);

   2. oculomotor disorders - double Vision (diplopia), strabismus, nystagmus, as well as symptoms of other cranial nerve palsies (such as peripheral Facial Nerve palsy) resulting from brainstem lesions;

   3. motor disorders - central mono-, hemi-, or paraparesis accompanied by hyperactive tendon and periosteal Reflexes, absent abdominal reflexes, increased Muscle tone, and pathological plantar and hand signs due to damage to the corticospinal pathways at various levels of the brain and spinal cord;

   4. ataxic disorders - gait unsteadiness, intention tremor, and scanning speech resulting from cerebellar and spinocerebellar pathway involvement;

   5. sensory disturbances - impaired Proprioception leading to sensory ataxia, and less commonly, alterations in pain and Temperature Sensation due to involvement of sensory pathways at various levels of the brain and spinal cord;

   6. neuropsychological disorders - memory impairment, euphoria, and depression resulting from widespread white matter damage in the brain;

   7. pelvic organ dysfunctions - urgency, urinary retention, and incontinence resulting from damage to the motor PATHWAYS OF THE brain and spinal cord.

The cerebrospinal form of MS, characterized by a combination of cerebral and spinal cord symptoms, is the most frequently observed. Other forms are less common, such as the spinal form (where spinal cord involvement predominates), the cerebellar form (centered on coordination deficits), and a variant marked by prominent hyperkinetic disorders (hyperkinetic form of MS).

Typically, the initial symptoms of the disease appear in young individuals, pointing to damage in a single region of the nervous system, and frequently undergo spontaneous resolution. Not infrequently, the disease begins with visual (retrobulbar neuritis) or oculomotor disturbances. The progression of MS is accompanied by the emergence of signs indicating involvement of other CNS regions. Even at the very onset of the disease, certain Characteristic Features of MS clinical manifestations may be detected: the loss of abdominal reflexes, decreased vibratory sensation, and markedly hyperactive tendon reflexes. A characteristic feature is the fluctuation in the severity of MS symptoms not only over months or weeks, but even within the course of a single day. A predictable exacerbation of neurological symptoms occurs with overheating, which is attributed to the heightened vulnerability of demyelinated fibers to environmental factors. The well-known phenomenon of the "dissociation of clinical manifestations" in MS (D. A. Markov, A. L. Leonovich) refers to various inconsistencies in nervous system symptoms—for instance, when a single patient exhibits a combination of lesions in different conducting pathways or at different anatomical levels.

Course of Multiple Sclerosis

Most commonly (in approximately 85% of patients), MS presents with a relapsing-remitting course, where periods of exacerbation alternate with periods of remission. Initially, an exacerbation may culminate in almost complete regression of neurological deficits. However, over time, subsequent relapses—characterized by the worsening of existing neurological symptoms or the appearance of new ones—no longer resolve completely. This leads to the establishment of persistent neurological deficits. As time progresses, the disease evolution takes on a more monotonous character with a gradual, steady deterioration in the patient's condition.

In some patients (10–15%), the disease may adopt a progressive course right from the outset, devoid of clearly demarcated periods of exacerbations and remissions. Nevertheless, the rate at which neurological deficits develop and health declines can vary significantly from case to case. A rapid and relentless progression of symptoms is possible, leading to disability and loss of self-care abilities within several months. Conversely, instances of slow disease progression and stabilization are also observed, allowing certain patients to maintain their working capacity and accustomed lifestyle for decades.

In certain instances, disease relapses can be linked to METABOLISM/18.html">The Influence of triggering factors: infections, hypothermia, physical exhaustion, trauma, surgical Procedures, intoxications, and psycho-emotional stress.

It should be noted that the emergence of neurological deficits during an MS relapse is driven by The Development of new demyelinating plaques. However, in some cases, depending on the anatomical Location OF THE lesions, this process may remain subclinical and can only be detected via MRI scans. The gradual smoothing out of the relapsing-remitting course in the late Stages of the disease is explained by the asynchronous development of demyelinating lesions across different Regions of the Central Nervous System.

In addition to true MS relapses caused by the emergence of new demyelinating lesions, patients may experience periods of decompensation driven by a complex of nonspecific changes within the central nervous system and the patient's body as a whole. Typically, these periods are characterized by the aggravation of pre-existing symptoms alongside the onset of general cerebral and somatic disorders.

The life expectancy of MS patients ranges from several years to 30–40 years. Patients usually succumb to secondary complications such as Pneumonia, Sepsis, or Urinary Tract infections.

Diagnosis and Cytology/practical/136.html">Differential diagnosis OF Multiple Sclerosis

There are no pathognomonic symptoms for MS. Therefore, diagnosing MS relies on identifying multifocal lesions within the nervous system, a characteristic combination of neurological symptoms, and a fluctuating, wave-like course of the disease. Consequently, a diagnosis of MS can only be confirmed or ruled out following a comprehensive evaluation and ongoing clinical monitoring. It should be emphasized that the presence of multiple demyelinating lesions cannot be considered strictly specific to MS, as inflammatory changes in brain tissue with myelin destruction are also found in many other pathological conditions of the nervous system.

The disseminated nature of CNS involvement is confirmed by symptoms whose presence cannot be explained by a single focal brain lesion or by MRI findings. Brain and spinal cord MRI allows for the detection of demyelinating lesions in 90% of cases and even makes it possible to assess the stage of their development. Neurophysiological Methods—such as The Study of visual, somatosensory, and short-latency brainstem auditory evoked potentials—enhance diagnostic reliability by uncovering subclinical focal CNS lesions. During acute exacerbations, some patients exhibit a slight elevation in protein levels and moderate pleocytosis (15–20 Cells per 1 mm³). Oligoclonal IMMUNOGLOBULINS, although not strictly specific to MS, can be detected in the CEREBROSPINAL FLUID of 80–90% of patients. Peripheral Blood immune profile changes are not definitive for MS diagnosis and generally reflect a broad spectrum of pathological and compensatory reactions.

The degree of diagnostic certainty in MS varies, classified as definite, probable, or possible. A definite diagnosis of MS is based on the documented occurrence of two or more relapse episodes lasting at least 24 hours, separated by an interval of at least 30 days, along with clinical and/or radiological evidence of dissemination of demyelinating CNS lesions in space and time.

At various stages of its progression, MS must be differentiated from brain and spinal cord tumors, degenerative Diseases of the nervous system, and vertebrogenic spinal cord disorders. A thorough medical history, MRI findings, and careful clinical follow-up provide invaluable assistance in this differential diagnosis.

Treatment of Multiple Sclerosis

The primary therapeutic goals in MS are to limit nervous system damage occurring during acute relapses, prevent subsequent attacks, and thereby halt disease progression and the accumulation of permanent neurological deficits. Based on current understanding of the Pathophysiology of MS, the following pathogenetic and symptomatic treatment approaches and agents are employed.

Glucocorticoids are most effective in suppressing the inflammatory and autoimmune processes within the nervous system that lead to myelin breakdown during acute relapses. However, they are unable to alter the long-term course of the disease. The traditional regimen for oral prednisolone involves prescribing 1–1.5 mg per 1 kg of body weight for no more than 2 weeks, followed by a gradual taper over 1.5 months.

Currently, methylprednisolone pulse therapy is preferred. It is administered intravenously at a dose of 500–1000 mg per day in an isotonic sodium chloride solution for 3–5 days (with an infusion time of at least 30 minutes). This may be followed by a short course of oral maintenance therapy with prednisolone. Alternatively, methylprednisolone tablets can be used at a dose of 80 mg every other day with a gradual dose reduction. Dexamethasone may also be administered intravenously at 8 mg twice daily, tapering the dose by 2 mg every 2 days.

Prolonged, multi-month corticosteroid therapy is discouraged. To mitigate the side effects of glucocorticoid treatment, the concurrent use of antiulcer medications and potassium-rich foods (such as bananas) is recommended.

If glucocorticoid therapy fails to yield the desired effect, cytotoxic agents (such as azathioprine or cyclophosphamide) may be employed. Their use is indicated in the relapsing-remitting and chronic progressive forms of MS, though it is frequently associated with A number of serious side effects and complications.

Plasmapheresis has demonstrated high efficacy during MS exacerbations (performed once a week with a plasma exchange volume equal to 5% of body weight, for a total of 4–10 sessions), particularly when combined with concurrent glucocorticoid administration.

One of the most promising avenues in MS immunotherapy is The Use of β-interferon-1b (Betaferon) and β-interferon-1a (Rebif, Avonex). They are capable of limiting CNS damage, likely by antagonizing pro-inflammatory cytokines—namely γ-interferon and tumor necrosis factor-alpha. Their administration in relapsing-remitting MS reduces disease activity and the frequency of relapses, although it does not reverse pre-existing MS symptoms. Reported side effects include fever, myalgia, fatigue, and local Skin irritation.

Antigen-specific immunotherapies include glatiramer acetate (Copaxone), a synthetic polymer composed of four Amino Acids (L-Alanine, L-glutamine, L-Lysine, and L-Tyrosine) that serves as an analogue of myelin basic protein. By competing with it, Copaxone protects myelin from destruction. It is believed that long-term administration of Copaxone can reduce the frequency of MS exacerbations. Encouraging results regarding the reduction of MS relapse rates have also been achieved with teriflunomide and Monoclonal Antibodies (natalizumab).

Nonspecific inflammatory reactions play a certain role in the pathogenesis of MS, particularly during the relapse phase. As adjunctive therapies to limit these changes and accelerate remyelination, the use of angioprotectors, antiplatelet agents, antioxidants, and metabolic drugs is considered justified. For this purpose, dipyridamole (Persantine), pentoxifylline (Trental), glutamic acid, alpha-tocopherol, Vitamins, and Hemodez are recommended.

Thus, the most effective and well-validated treatments for MS are glucocorticoids (methylprednisolone pulse therapy) and plasmapheresis—aimed at shortening the duration of acute relapses—as well as β-interferon, which slows the progression of the pathological process. At the same time, none of these treatment methods possesses absolute efficacy or guarantees the complete reversal of neurological deficits. Consequently, adequate symptomatic treatment plays a vital role in the comprehensive care of MS patients, as it significantly improves their quality of life.

Major challenges in maintaining acceptable well-being and working capacity in MS patients include motor dysfunctions associated with spasticity and generalized fatigue, pelvic organ dysfunction, and various psychopathological symptoms.

To reduce limb muscle spasticity, medications such as Mydocalm, baclofen, tizanidine, and benzodiazepines (at doses that avoid exacerbating muscle weakness) are used, alongside acupuncture and acupressure. Pronounced coordination disorders and intention tremor can be alleviated by administering Vitamin B6 and beta-blockers. Symptoms of depression and emotional lability require the use of antidepressants and psychotherapy. Pelvic organ dysfunctions are managed with anticholinergic drugs and physical therapy, alongside the use of urinary antiseptics. Periodic courses of metabolic agents (such as Cerebrolysin, Cortexin, piracetam, etc.) are also advisable.

Prevention of Multiple Sclerosis

Primary prevention for MS has not been established. Secondary prevention should focus on avoiding exhausting physical exertion, overheating, and excessive sun exposure (hyperinsolation).