NEUROLOGY AND NEUROSURGERY - Y. V. ALEKSEEENKO - 2014

NEUROMUSCULAR DISEASES

Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder caused by The formation of autoantibodies against postsynaptic Membrane Receptors, resulting in subsequent membrane damage and a block in neuromuscular transmission. Myasthenia gravis manifests as Muscle weakness and pathological muscle fatigability. In some cases, The Development of myasthenia gravis is associated with thymic hyperplasia or thymoma. In addition to myasthenia gravis, myasthenic syndromes can occur secondary to systemic disorders (such as polymyositis and dermatomyositis) and oncological diseases (such as lung, breast, ovarian, and prostate Cancer), which may involve autoimmune damage to both presynaptic and postsynaptic structures.

The prevalence of myasthenia gravis ranges from 10 to 24 cases per 100,000 population across various countries. There is reason to believe that the condition is somewhat more common than previously thought, as some cases remain undiagnosed in a timely manner. Women are affected three times more frequently than men, and the disease typically onset in young or middle adulthood. The hallmark of the diverse clinical manifestations of myasthenia gravis is The phenomenon of pathological muscle fatigability. Muscle weakness noticeably increases with repetitive movements and worsens following exertion in the afternoon or evening. It improves after rest or the administration of anticholinesterase drugs.

Myasthenia gravis is classified into generalized and ocular forms. In the ocular form, characteristic disease manifestations are limited to extraocular muscle involvement. This results in double Vision (diplopia) and strabismus, as well as unilateral or bilateral ptosis, which worsen following exertion (such as reading or sustained fixation of gaze) or toward the end of the day. Weakness of the facial, masticatory, and Tongue Muscles is frequently observed, leading to difficulties in articulation, chewing, and swallowing that may emerge during conversation or meals. Pathological muscle fatigability and weakness of the striated Muscles of the neck, trunk, and limbs lead to a significant restriction in the range of motion and overall patient mobility. HEAD drop may occur, and patients sometimes require external support to maintain trunk and limb posture, among other manifestations. The generalized form of myasthenia gravis may be accompanied by respiratory dysfunction. In severe cases, sphincter weakness occurs, leading to urinary and fecal incontinence.

The clinical course is typically chronic and progressive, punctuated by periodic exacerbations and remissions. A rapid onset of decompensation (myasthenic crisis) with life-threatening disruption of vital Functions is possible. The triggers for such catastrophic deterioration are not always clear; sometimes this state is provoked by infection, intoxication, or the administration of certain medications that exacerbate impairments in neuromuscular synaptic transmission. In such patients, generalized muscle weakness rapidly escalates, extraocular and bulbar symptoms (dysphonia, dysarthria, and dysphagia) intensify, respiratory disorders appear, hypoxic encephalopathy with altered consciousness develops, and severe autonomic dysregulation ensues. Without appropriate Treatment, a fatal outcome is possible.

Myasthenia gravis is diagnosed based on typical clinical Complaints underpinned by the phenomenon of pathological muscle fatigability. Impairments in neuromuscular transmission can be confirmed using repetitive nerve stimulation electromyography. The proserine (neostigmine) test is informative: significant symptom alleviation is observed 30–60 minutes after the subcutaneous injection of 1–2 ml of a 0.05% proserine solution, which can also be corroborated by electromyographic studies. The detection of a thymoma is achieved via CT or MRI of the Mediastinum. An elevated serum level of autoantibodies against muscle acetylcholine receptors is considered one of the primary diagnostic Criteria for the disease. Furthermore, the dynamics of this parameter reflect the efficacy of Pathogenetic Therapy.

Myasthenia gravis must be differentiated from botulism, multiple sclerosis, Brainstem encephalitis, AMYOTROPHIC LATERAL SCLEROSIS, brainstem tumors, Basal meningitis, myopathy, polymyositis, cerebrovascular disorders in the vertebrobasilar system, and Lambert-Eaton myasthenic syndrome.

To restore neuromuscular transmission, anticholinesterase medications are prescribed—such as neostigmine methylsulfate (proserine), pyridostigmine bromide (kalymin)—along with neuromidin, potassium supplements, and potassium-sparing Diuretics. Autoimmune abnormalities are managed using corticosteroids or cytostatic agents. In cases of myasthenic crisis, high doses of corticosteroids (methylprednisolone) are administered, along with hemadsorption and plasmapheresis, supplemented by mechanical ventilation when necessary. Stabilization of immunopathological reactions can be achieved through the intravenous administration of human immunoglobulin. Fluid and electrolyte balance must be closely monitored and corrected. In the presence of a thymoma, involvement of craniobulbar muscles, or a progressive disease course, surgical intervention—thymectomy—is indicated. In some cases, gamma therapy targeting the Thymus region is performed.

It is crucial to remember that the administration of high doses of anticholinesterase drugs can precipitate a cholinergic crisis, which manifests as bilateral miosis, salivation and increased bronchial secretions, hyperperistalsis, and bradycardia. However, recognizing and differentiating this state from a myasthenic crisis is often challenging. To relieve a cholinergic crisis, the administration of anticholinesterase drugs is discontinued, and atropine is prescribed.

In patients with myasthenia gravis, excessive physical exertion, sun exposure (insolation), alcohol consumption, magnesium preparations, curare-like muscle relaxants, neuroleptics, and tranquilizers (except tofisopam), diuretics (except spironolactones), Aminoglycosides, fluoroquinolones, fluorinated corticosteroids, quinine derivatives, and D-penicillamine are contraindicated. Timely Diagnosis and appropriate treatment of myasthenia gravis enable the achievement of stable compensation of motor disorders in 80% of patients.

Myotonias

Myotonias represent a heterogeneous group of neuromuscular disorders characterized by the presence of a myotonic phenomenon in their clinical profile, which manifests as an impaired ability of muscles to relax rapidly following active contraction. The prevalence of the disease is approximately 0.3–0.7 per 100,000 population. Thomsen's disease is inherited in an autosomal dominant manner, whereas the autosomal recessive variant (Becker's disease) is somewhat less common. The onset typically occurs in childhood or adolescence. Pronounced contraction of the hand and leg muscles, forceful jaw closure involving the masticatory muscles, and tight eye closure are accompanied by tonic muscle spasms and delayed relaxation. Repetitive movements alleviate myotonic stiffness (the "warm-up" phenomenon). Delayed muscle relaxation creates difficulties when executing complex motor tasks that require alternating activity across different muscle groups, as well as when acquiring complex motor skills (such as riding a bicycle or participating in active sports), thereby predisposing individuals to unexpected falls and increasing the risk of injury. Mechanical hyperexcitability of the muscles is frequently observed. Most individuals with myotonia exhibit an athletic

build, likely resulting from moderate diffuse hypertrophy across various muscle groups. Objective Examination reveals reduced muscle strength, although the muscles feel remarkably firm upon Palpation. Tendon Reflexes are generally normal. The disease follows a slowly progressive course; however, many patients maintain their working capacity for extended periods.

The diagnosis is established based on the characteristic myotonic phenomenon, findings from electroneuromyography (demonstrating a myotonic discharge pattern), and molecular genetic testing. The severity of myotonic manifestations can be moderately alleviated by the administration of diphenylhydantoin, diamox, calcium supplements, and procainamide.

Clinical Cases

Case 1

A 32-year-old woman reports a several-month history of diplopia and left-sided ptosis, which tend to develop gradually while reading. Recently, she has also experienced a sensation of tension and dull pain in the neck and occipital region that intensifies toward the end of the day, alongside rapid fatigue of the facial and masticatory muscles during speech and mastication of solid foods. These symptoms are accompanied by articulation impairments, changes in voice timbre, and swallowing difficulties. She also notes rapid fatigue when working with her arms raised. During a recent common cold, she experienced a severe deterioration characterized by a dramatic exacerbation of the aforementioned symptoms and profound generalized weakness. Physical examination reveals Asymmetry of the palpebral fissures. No significant abnormalities in muscle strength, tone, or tendon reflexes are detected at the time of examination.

   • List the primary neurological abnormalities.

   • Identify the leading neurological syndrome.

   • Determine the muscle groups involved in the pathological process.

   • Formulate a preliminary clinical diagnosis.

   • Explain the pathophysiological mechanism of this disorder.

   • How do muscle weakness and fatigability in this condition differ from the motor deficits seen in conventional paresis and paralysis?

   • Name the tests that confirm the specific nature of motor impairments in this condition.

   • Name the essential instrumental neurological examination Methods.

   • Describe the somatic examination protocol.

   • List common pathological conditions accompanied by muscle weakness and fatigue.

   • How should an episode of health deterioration triggered by a cold be classified?

   • What circumstances can provoke the development of decompensation and crisis states?

   • Name the MAIN TYPES OF crisis states associated with this disease.

   • What are the risks associated with disease progression and worsening symptoms?

   • What substances and medications can exacerbate the manifestations of this disease?

   • List the main conservative treatment methods.

   • Describe the goals and principles of Surgical treatment.

   • Describe the management protocol for a myasthenic crisis.

   • Outline the specific considerations for managing patients with myasthenia gravis during Pregnancy.

Option 2

A 21-year-old male presents with sudden muscle stiffness and difficulty relaxing muscles at the onset of rapid, intensive movements in his upper and lower limbs. Repeating the movements relieves the muscle spasm. Slow movements are performed without difficulty. Muscle stiffness is notably aggravated by cold. During physical education at school, he noticed some clumsiness during fast movements compared to his peers. During his military service, he consistently lagged behind in drill and physical exercises. He is referred to the hospital for evaluation. The muscles are well-developed and firm to the Touch. Muscle strength is slightly reduced. Tendon reflexes are normal.

   • Identify the primary symptom complex.

   • Formulate a preliminary clinical diagnosis.

   • Explain the pathophysiological mechanism of this condition.

   • Which muscle groups are most frequently involved in the pathological process?

   • Propose tests to establish The Nature of motor impairments in this condition.

   • Name the essential instrumental neurological examination methods.

   • Outline the main directions for Differential diagnosis.

   • What role might genetic factors play in the development of this disease?

   • Describe the treatment for this condition.

   • Determine the prognosis for the disease

  • Formulate recommendations for the patient.

Option 3

A 24-year-old woman complains of weakness in her arms and legs. At about 10 years of age, she noticed she was falling behind her peers in running and active games. Gradually, she developed noticeable weakness in her legs, followed by the shoulder girdle and arm muscles. Raising her arms above her head became difficult. People around her noticed a waddling gait. Examination reveals Atrophy of the facial muscles, shoulder girdle, arms, Pelvic Girdle, back, and leg muscles. Exaggerated lumbar lordosis. Muscle tone is decreased, tendon reflexes in the arms are depressed, and knee and ankle jerks are absent in the legs. There are no sensory disturbances. She rises from a lying position slowly and with difficulty, using surrounding objects. She straightens her trunk by pushing with her hands against her thighs. After squatting, she cannot stand up without the help of her hands.

  • List the main neurological disorders.

  • Determine the type of motor impairment.

  • Formulate a preliminary clinical diagnosis.

  • Outline the main directions for differential diagnosis.

  • Name the necessary supplementary diagnostic methods.

  • What is The Role of genetic factors in the development of this disease?

  • Based on what features can Various Forms of progressive muscular dystrophies be differentiated?

  • What visceral changes are observed in progressive muscular dystrophies?

  • Describe the management of this disease.

  • Determine the prognosis of the disease.