Guillain-Barré Syndrome (GBS)

Pathology of Peripheral Nerves & Muscles

• The pathology of peripheral nerves and muscles involves the study of axons, myelin sheaths, and Schwann cells.
• Injury to these components can result in peripheral neuropathy.
• Peripheral nerves are made up of axons and myelin sheaths formed by Schwann cells.

Peripheral Nerves

• Axons and myelin sheaths are vital for impulse transmission in peripheral nerves.
• Schwann cells produce the myelin sheath.
• Damage to axons or myelin can lead to peripheral neuropathy.
• The Node of Ranvier are unmyelinated gaps between the myelinated segments called internodes.
• In myelinated axons, individual Schwann cells create myelin sheaths that wrap around a single axon, thereby forming internodes separated by nodes of Ranvier.
• Nodes of Ranvier are evenly spaced along the axon.
• A peripheral nerve is composed of a bundle of nerve fibers which are further divided into fascicles, surrounded by connective tissue layers.

Normal Peripheral Nerve

• A peripheral nerve is composed of a bundle of nerve fibers.
• Connective tissue layers surround nerve fibers and fascicles.
• Epineurium surrounds the entire nerve.
• Perineurium surrounds a fascicle.
• Endoneurium surrounds an individual nerve fiber.
• Each nerve fiber is covered by a Schwann cell.
• The myelin sheath and axon are positioned correctly.

Normal Motor Units

• Two adjacent motor units are often shown in illustrations.
• The neurons, axons, and myocytes are depicted.
• Motor units represent functional groupings of neurons and muscle fibers.

Patterns of Peripheral Nerve Injury

• Peripheral nerve injury can be classified as axonal or demyelinating neuropathy.
• Axonal neuropathy is characterized by direct injury to the axon, leading to distal axon and myelin loss.
• Demyelinating neuropathies affect Schwann cells and myelin sheaths.

Axonal Neuropathies

• Direct injury to the axon causes its distal portion to degenerate.
• This is often associated with secondary myelin loss (Wallerian degeneration).
• Regeneration involves axonal regrowth and remyelination.

Axonal Degeneration

• Initial acute axonal injury results in progressive loss of the distal axon and myelin sheath.
• Denervated myofibers undergo atrophy.
• Wallerian degeneration includes swelling at the axon terminal followed by distal axon and myelin sheath breakdown, and phagocytosis of myelin debris.

Axon Regeneration

• Regeneration of axons after injury allows for reinnervation of myofibers.
• The regenerated axon is myelinated by proliferating Schwann cells.
• The new internodes are thinner than the original ones.

Demyelinating Neuropathies

• Schwann cells and their myelin sheaths are the primary targets of damage in demyelination.
• Injury to Schwann cells or myelin leads to demyelination.
• Demyelinating neuropathies often cause segmental demyelination in peripheral nerves.
• Axons in demyelination are often thin.
• Short internodes are commonly observed in demyelination.
• Nerve conduction velocities are often decreased in demyelinating neuropathies.

Segmental Demyelination

• Segmental demyelination is characterized by random degeneration of individual myelin internodes.
• Axons remain spared in segmental demyelination.
• Remission of demyelinating disease can lead to remyelination of the nerves that are affected, though internodes may be shorter, and the resulting myelin sheaths are typically thinner.

Disorders Associated With Peripheral Nerve Injury

• Inflammatory, infectious, hereditary, metabolic/toxic, and traumatic nerve injuries are categorized as distinct causes for nerve abnormalities.

Inflammatory Neuropathies

• Some examples include Guillain-Barré Syndrome (GBS), infectious polyneuropathies (e.g., leprosy, diphtheria, and varicella-zoster virus (VZV)), and immune-mediated neuropathies.
• GBS is a rapidly progressive, immune-mediated demyelinating neuropathy.
• Early GBS involves motor axons.
• The condition can lead to life-threatening respiratory paralysis.

Pathogenesis of Guillain-Barré Syndrome

• Immune-mediated demyelination is usually caused by an acute onset.
• Immune responses from T and B cells play a role.
• Cross-reactive antibodies against components of peripheral nerves may contribute to the condition.
• GBS may occur after infections or vaccinations.

Morphology of Guillain-Barré Syndrome

• Inflammation of peripheral nerves, showing perivenular and endoneurial infiltration of cells including lymphocytes, macrophages, and plasma cells.
• Segmental demyelination damage to peripheral nerves is the prominent feature.
• Axonal damage, particularly in severe cases.

Treatment of Guillain-Barré Syndrome

• Plasmapheresis and intravenous immunoglobulin (IVIg) are used to remove antibodies.
• Supportive care is provided, including ventilatory support.

Infectious Neuropathies

• Various infectious agents affect peripheral nerves.
• Examples include leprosy, diphtheria, and varicella zoster virus (VZV).

Leprosy

• Related to mycobacteria, causing segmental demyelination and loss of both myelinated and unmyelinated axons.
• Lesions may show endoneurial fibrosis and thickening of perineurial sheaths with progression of leprosy.

Lepromatous Leprosy

• Marked skin involvement with infiltration by macrophages.
• Loss of sensation, particularly in extremities.

Tuberculoid Leprosy

• Cell-mediated immune response causes nodular skin lesions with granulomas.
• Damage to nerves is limited to distal extremities.

Metabolic, Hormonal, and Nutritional Neuropathies

• Diabetes is the most frequent cause of peripheral neuropathy.
• Diabetic neuropathy involves autonomic neuropathy, lumbosacral radiculopathy, and or distal symmetric sensorimotor polyneuropathy (or combinations).
• Autonomic neuropathy leads to disorders in bowel, bladder, cardiac, or sexual function.

Diabetic Peripheral Neuropathy

• Diabetes mellitus causes complex metabolic and secondary vascular changes.
• These changes affect the peripheral axons and Schwann cells, causing damage.
• The presence of advanced glycosylation products, hyperglycemia, and increased levels of reactive oxygen species, microvascular changes, and changes to axonal metabolism are believed to contribute to the pathogenesis of diabetic peripheral neuropathy.

Diabetic Peripheral Neuropathy —Symptoms

• Distal symmetric sensorimotor polyneuropathy.
• Paresthesias and numbness in extremities.
• Both axonal and demyelinating features are seen in diabetic neuropathy.

Neuropathies Associated with Malignancy

• These neuropathies may result from local effects, complications of cancer therapy, or paraneoplastic syndromes.
• Direct infiltration or compression of nerves by tumors may cause mononeuropathy.
• Tumors located in specific areas can cause brachial plexopathy, or obturator palsy.
• Intracranial tumors can produce cranial nerve palsies.

Toxic Neuropathies

• Exposure to industrial chemicals, biological toxins, or therapeutic drugs can cause peripheral neuropathies.
• Toxic agents include alcohol, heavy metals (lead, mercury, arsenic, and thallium), and organic solvents.

Traumatic Neuropathies

• Peripheral nerves are affected by trauma or entrapment.
• Lacerations, or avulsion, can result from sharp or cutting injuries such as fragments of fractured bones, applied force or tension, commonly to limbs.
• Compression neuropathy can result from pressure to peripheral nerves.
• Carpal tunnel syndrome is the most frequent entrapment neuropathy, due to pressure on the median nerve.

Inherited Peripheral Neuropathies

• These neuropathies display diverse genetic and phenotypic features, including motor, sensory, or autonomic dysfunction.
• Examples include Charcot-Marie-Tooth (CMT) disease, which is caused by mutations affecting either peripheral nerve axons or myelin sheaths.
• Hereditary motor (neuropathies) and sensory neuropathies are forms of inherited peripheral neuropathy, as are other inherited genetic conditions and inherited metabolic diseases.

Traumatic Neuromas

• These neuroma growths can result from discontinuities between distal and proximal portions of nerve tissue, and misalignment in fascicles.
• The resulting mass of tangled axonal processes is within the thickened nerve tissue.
• Schwann cells, fibroblasts, and perineural cells surround the bundles of axons.

Disorders of Neuromuscular Junction

• Diseases of the neuromuscular junction typically involve functional abnormalities rather than observable structural changes.
• Myasthenia gravis (MG) is an example, in which autoantibodies block acetylcholine receptors on motor endplates.

Myasthenia Gravis

• Autoantibodies block acetylcholine receptors at motor endplates.
• Degradation and depletion of receptors is common.
• This impacts the function of these receptors.
• This condition may occur at any age, often presenting in females.
• Approximately 60% of cases are associated with intrathmic B-cell hyperplasia and/or thymoma.

Myasthenia Gravis —Symptoms

• Weakness in extraocular muscles (ptosis or diplopia).
• Facial muscles are typically spared.
• Cholinesterase inhibitors often improve symptoms.
• Treatment usually involves thymoma removal or plasmapheresis.

Disorders of Skeletal Muscle

• Fiber types include slow twitch (aerobic, type I) and fast twitch (anaerobic, type II).
• The checkerboard pattern of myofibers is common.
• Skeletal muscle function depends on the unique protein complexes that make up the sarcomeres (contractile units) and the dystrophin-glycoprotein complex.

Dystrophinopathies

• Duchenne and Becker muscular dystrophies are the most common types.
• DMD is characterized by complete absence of dystrophin.
• Disease severity correlates.

Morphology of Duchenne Muscular Dystrophy

• Ongoing myofiber necrosis and regeneration in the muscle.
• Progressive fibrosis and fat replacement of the muscle.
• Marked variability in myofiber size and abnormal positioning of muscle nuclei.
• Cardiac muscle can display myofiber hypertrophy and fibrosis.

Pathogenesis of Duchenne Muscular Dystrophy

• Mutations occur on the Xp21 gene that encodes dystrophin.
• Cardiac involvement (Cardiomyopathy) can be present.
• Muscle biopsies commonly show absence of dystrophin.

Acquired Disorders of Skeletal Muscle (Inflammatory and Toxic)

• Inflammatory myopathies, such as polymyositis and dermatomyositis, and toxic myopathies (associated with toxins, and certain drugs) are categorized as 'acquired'.
• The two most frequently seen inflammatory myopathies are polymyositis and dermatomyositis.
• Features of the diseases such as polymyositis, may show endomysial inflammation and myofiber necrosis.

Polymyositis

• Inflammatory myopathy.
• Characterized by endomysial inflammation and myofiber necrosis.
• Lacks the cutaneous features seen in dermatomyositis.

Dermatomyositis

• Inflammatory condition affecting, skin and skeletal muscles.
• Characterized by the presence of a characteristic heliotrope rash, often on eyelids.
• Perifascicular atrophy is a notable histological/microscopic feature.

This quiz covers the key aspects of Guillain-Barré Syndrome (GBS), including segmental demyelination, pathological processes affecting motor axons, immunological mechanisms, cellular infiltrates, therapeutic interventions, and clinical characteristics. Also includes infectious agents associated with triggering GBS and pathological changes in severe cases.