Guillain-Barrв€љВ© & Charcot-Marie-Tooth

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Pathophysiology

Summary

Guillain-Barré syndrome (GBS) is an immune-mediated demyelinating disorder targeting the peripheral nervous system, sometimes referred to as ‘acute inflammatory demyelinating polyradiculoneuropathy’. GBS may be caused by an inappropriate immune response following an infection, resulting in molecular mimicry, where the antigen of the pathogen cross-reacts with components of the peripheral nerves. Schwann cells, the main producers of myelin in the peripheral nerves, are the primary target of this autoimmune response.

Campylobacter jejuni, an S-shaped gram-negative bacterium, is the most frequent precipitating organism linked to GBS. Additionally, viral infections such as HIV, EBV, CMV & upper respiratory infections can instigate GBS.

The pathogenesis of GBS incorporates both cellular and humoral immune responses. The cellular immune response includes the activation of helper T-cells that recruit macrophages, while a humoral response likely involves the autoantibody-mediated destruction of Schwann cells or myelin antigens. Additionally, local activation of the complement cascade from antibody binding may also play a role.

Histologically, GBS is characterized by an endoneurial inflammatory infiltrate around the peripheral myelin. Clinically, GBS presents with ascending symmetric muscle paralysis and decreased or absent DTRs. If the paralysis ascends high enough, it can lead to respiratory failure due to diaphragmatic and accessory respiratory muscle paralysis, as well as Bell’s palsy. A diagnostic hallmark in the CSF is the ‘albumino-cytologic dissociation’, denoted by a high protein level with a regular cell count, which results from increased capillary permeability at the blood-nerve barrier.

Charcot-Marie-Tooth (CMT) disease is a hereditary motor sensory neuropathy, impacting either the development of peripheral nerve axons or their myelin sheath. CMT is most commonly inherited in an autosomal dominant fashion, and causes demyelination & peripheral nerve axonal dysfunction, resulting from the defective production of proteins important for the structure & function of peripheral nerves and their myelin sheath.

Clinically, CMT manifests as progressive lower extremity weakness and atrophy, usually within the first two decades of life. CMT initially presents with foot drop due to lesions in the common fibular nerve. Over time, this can progress to musculoskeletal deformities like the high-arched foot deformity, or pes cavus, and thoracic kyphoscoliosis due to nerve and muscle atrophy of the foot and trunk. Sensory loss such as impaired proprioception, vibration sense, and discriminate touch are also observed.

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FAQs

What are the key distinguishing features and presentations of Guillain-Barré syndrome (GBS)?

Guillain-Barré syndrome (GBS) typically presents with symmetric ascending muscle paralysis, starting from the lower extremities. It also often features decreased or absent deep tendon reflexes (DTRs). In severe cases, GBS may cause bilateral facial paralysis or respiratory failure due to the paralysis of motor neurons. Additionally, GBS is loosely associated with an antigen from pathogen cross-reacting with peripheral nerve components, also known as ‘molecular mimicry.’ Infections such as Campylobacter jejuni and various viral infections can instigate this process.

How does Charcot-Marie-Tooth (CMT) disease affect the peripheral nervous system?

Charcot-Marie-Tooth disease is a genetic disorder that affects the development of peripheral nerve axons or their myelin sheath. It is most commonly inherited in an autosomal dominant fashion, and results from the defective production of proteins that are critical for the structure and function of peripheral nerves and their myelin sheath. This leads to demyelination and axonal dysfunction of peripheral nerves.

What are clinical manifestations are associated with Charcot-Marie-Tooth (CMT) disease?

Charcot-Marie-Tooth (CMT) disease typically presents with progressive lower extremity weakness and atrophy, usually developing within the first two decades of life. This can eventually lead to a high-arched foot deformity known as ‘pes cavus’, due to atrophy of nerves and muscles of the foot. Over time, it can cause thoracic kyphoscoliosis, a curvature of the spine in both coronal and sagittal planes. Apart from motor symptoms, patients may also experience sensory loss, particularly proprioception, vibration, and discriminate touch.

What is the role of the immune system in the pathogenesis of Guillain-Barré syndrome (GBS)?

The pathogenesis of Guillain-Barré syndrome (GBS) involves both cellular and humoral immune responses. The cellular immune response includes the activation of helper T-cells that recruit macrophages, while the humoral response involves the autoantibody-mediated destruction of Schwann cells or myelin antigens. Additionally, local activation of the complement cascade from antibody binding may also play a role.

What is the difference in pathogenesis between Guillain-Barré syndrome and Charcot-Marie-Tooth disease?

Guillain-Barré syndrome is typically precipitated by an inappropriate immune response to a previous infection. The autoimmune response in GBS specifically targets Schwann cells—responsible for producing the myelin sheath of peripheral nerves—leading to segmental demyelination throughout the peripheral nerves. In contrast, Charcot-Marie-Tooth disease is a hereditary motor sensory neuropathy caused by the defective production of proteins important for the structure and function of peripheral nerves and their myelin sheath. This leads to demyelination and axonal dysfunction of peripheral nerves.