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Schwann cells embryologically derive from the neural crest. They myelinate peripheral nerves and serve as the primary glial cells of the peripheral nervous system (PNS), insulating and providing nutrients to axons. Myelination increases conduction velocity along the axon, allowing for the saltatory conduction of impulses.[1] Nonmyelinating Schwann cells do not wrap axons to improve conduction, but still, provide trophic support and cushioning to the unmyelinated axons.[2]

The major diseases involving Schwann cells are demyelinating or neoplastic processes. Disorders that cause damage to the myelin sheath in the PNS, affecting the function of Schwann cells and axons, are called peripheral demyelinating diseases. Various insults, such as genetic mutations, infections, trauma, and autoimmune processes can trigger this demyelination and eventual neurodegeneration. Guillain-Barre Syndrome is a rare autoimmune peripheral demyelinating disease characterized by acute ascending flaccid paralysis, which can be life-threatening if the disease affects the muscles of respiration. It is often associated with a preceding infection of the gastrointestinal or respiratory tract, particularly C. jejuni and associated anti-GM1 and anti-GD1a antibodies. The association with infection and accumulation of anti-ganglioside antibodies suggests that ganglioside-like antigens found on C. jejuni lead to the production of antibodies that are cross-reactive with myelinating cells of the PNS. Guillain-Barre can also be caused by other pathogens, trauma, surgery, monoclonal antibody treatment, and rarely by vaccination. The patients usually present with proximal muscle weakness of lower extremity. The most common variant of Guillain-Barre is acute inflammatory demyelinating polyradiculopathy (AIDP), which presents histologically with segmental demyelination with lymphocytic and monocytic infiltration.[13][14] Charcot-Marie-Tooth disease (CMT) is a rare hereditary peripheral demyelinating disorder, most commonly with autosomal dominant inheritance. Several subtypes affect different proteins and can affect both sensory and motor nerves, but all disrupt Schwann cell structure and function. PMP22 is the most commonly affected protein and causes CMT1A, leading to growth arrest in Schwann cells and abnormal Schwann cell number between nodes of Ranvier. CMT1 is characterized by segmental demyelination and remyelination, causing onion skin appearance on biopsy, and greatly reduced conduction velocity of nerves.[13][15]

Charcot-Marie-Tooth disease (CMT) is a rare hereditary peripheral demyelinating disorder, most commonly with autosomal dominant inheritance. Several subtypes affect different proteins and can affect both sensory and motor nerves, but all disrupt Schwann cell structure and function. PMP22 is the most commonly affected protein and causes CMT1A, leading to growth arrest in Schwann cells and abnormal Schwann cell number between nodes of Ranvier. CMT1 is characterized by segmental demyelination and remyelination, causing onion skin appearance on biopsy, and greatly reduced conduction velocity of nerves.[13][15] Diabetes mellitus is associated with hyperglycemia, hyperlipidemia, hypertension, and impaired insulin signaling, which can damage microvasculature, leading to the common complication of diabetic peripheral neuropathy. Diabetic neuropathy is due to damage to Schwann cells and axons in both sensory and motor nerves. Schwann cells appear to be more susceptible to direct damage caused by hyperglycemia. In contrast, neurons are highly metabolically active, and function better in a hyperglycemic environment but are at greater risk of degeneration caused by hypoxia and loss of trophic support from Schwann cells. Hyperglycemia causes Schwann cell dysfunction, production of reactive oxygen species, initiation of the inflammatory cascade, disruptions in axon conduction, and impaired regeneration after nerve damage.[2]

Diabetes mellitus is associated with hyperglycemia, hyperlipidemia, hypertension, and impaired insulin signaling, which can damage microvasculature, leading to the common complication of diabetic peripheral neuropathy. Diabetic neuropathy is due to damage to Schwann cells and axons in both sensory and motor nerves. Schwann cells appear to be more susceptible to direct damage caused by hyperglycemia. In contrast, neurons are highly metabolically active, and function better in a hyperglycemic environment but are at greater risk of degeneration caused by hypoxia and loss of trophic support from Schwann cells. Hyperglycemia causes Schwann cell dysfunction, production of reactive oxygen species, initiation of the inflammatory cascade, disruptions in axon conduction, and impaired regeneration after nerve damage.[2] Schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNSTs) are all neoplastic conditions that arise from Schwann cells. Schwannomas are typically solitary encapsulated lesions made exclusively of neoplastic Schwann cells. Schwannomas do not invade the associated nerve but may produce symptoms caused by mass effect. Neurofibromas and MPNSTs are made of multiple cell types, including Schwann cells, and commonly infiltrate the associated nerve. Neurofibromas commonly arise in patients with neurofibromatosis 1 (NF1), an autosomal dominant disorder caused by a mutation in the NF1 tumor suppressor gene, which may present with dermal and/or plexiform neurofibromas. Dermal neurofibromas are hormone-sensitive tumors that begin to appear as NF1 patients enter puberty, and these tumors have little to no malignant potential. Plexiform neurofibromas are often congenital, not hormone-responsive, and can undergo malignant transformation to MPNSTs.[16][17]