PNS Demyelinating Disorders Notes

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This Osmosis High-Yield Note provides an overview of PNS Demyelinating Disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about PNS Demyelinating Disorders by visiting the associated Learn Page.
NOTES NOTES PNS DEMYELINATING DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Progressive peripheral nervous system (PNS) disorders; destruction of myelin, disruption of motor, sensory function TYPES Charcot–Marie–Tooth disease ▪ Genetic mutations → defective myelin sheath, impaired neuronal mitochondrial function Guillain–Barré syndrome ▪ Acute triggering event (e.g. infection) → aberrant autoimmune response → myelin sheath destruction COMPLICATIONS Charcot–Marie–Tooth disease ▪ Muscle atrophy, impaired ambulation, foot irregularities Guillain–Barré syndrome ▪ Respiratory failure, cardiac arrhythmias, quadriplegia SIGNS & SYMPTOMS ▪ ↓/absent deep tendon reflexes, paresthesia, muscle weakness, ↓ touch sensation DIAGNOSIS DIAGNOSTIC IMAGING Gadolinium-enhanced MRI ▪ Guillain–Barré ▫ Intrathecal spinal nerve root thickening 676 OSMOSIS.ORG LAB RESULTS ▪ Guillain–Barré ▫ Albuminocytologic dissociation in cerebrospinal fluid (CSF) OTHER DIAGNOSTICS ▪ Electromyography (EMG), nerve conduction studies (NCS) ▫ ↓/blocked nerve conduction velocity ▪ History, physical examination TREATMENT MEDICATIONS ▪ Guillain–Barré ▫ Intravenous immunoglobulin (IVIG) SURGERY ▪ Charcot–Marie–Tooth ▫ Correction of severe skeletal irregularities OTHER INTERVENTIONS ▪ Charcot–Marie–Tooth ▫ Genetic testing, orthotics, physical/ occupational therapy ▪ Guillain–Barré ▫ Plasmapheresis; supportive care (e.g. respiratory/hemodynamic support) ▪ Pain management ▫ Acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), gabapentin, carbamazepine
Chapter 87 PNS Demyelinating Disorders CHARCOT–MARIE–TOOTH DISEASE osms.it/Charcot-Marie-Tooth PATHOLOGY & CAUSES ▪ Group of hereditary, progressive neurological disorders; disruption of PNS processes, impaired sensory/motor function ▪ Genetic mutations → defective structure, function of proteins in myelin sheath/ neuron’s axon ▪ Classification: Types I-VII; Type X (X-linked) ▫ Subtypes based on associated genes and phenotypes TYPES SIGNS & SYMPTOMS ▪ Onset in first to third decade of life, depending on type ▪ Progressive distal muscle weakness; atrophy of hands, feet ▪ Distal sensory loss, paresthesias, loss of proprioception ▪ ↓ deep tendon reflexes, areflexia ▪ Foot irregularities ▫ Foot drop, high arches (pes cavus), hammer toes, flail foot, cavovarus foot ▪ Unsteady gait, toe-walking Charcot–Marie–Tooth I (CMT1) ▪ Demyelinating form ▫ Caused by mutations in PMP22, MPZ genes (encode for myelin sheath proteins) → ↓ nerve conduction velocity ▫ Autosomal dominant/sporadic inheritance CMT2 ▪ Axonal form ▫ Caused by mutations in MFN2 gene (encodes for mitofusin-2 protein in neuronal mitochondria) → neuronal death ▫ Autosomal dominant/recessive inheritance RISK FACTORS ▪ Inheritance of defective gene(s) COMPLICATIONS ▪ Muscle atrophy, loss of ambulation; deafness, intellectual disability, optic neuropathy, feeding difficulties, hip dysplasia Figure 87.1 An MRI scan of the foot of an individual with Charcot-Marie-Tooth disease. There is wasting of the plantar muscles and prominent pes cavus as well as a hammer irregularity of the great toe. OSMOSIS.ORG 677
DIAGNOSIS OTHER DIAGNOSTICS ▪ NCS, EMG ▫ ↓ nerve conduction velocity ▪ History, physical examination (e.g. age of onset) ▪ Genetic testing OTHER INTERVENTIONS ▪ Physical/occupational therapy ▫ Strengthening, range of motion, balance, maintenance of mobility, activities of daily living ▪ Orthotics TREATMENT MEDICATIONS ▪ Pain management ▫ Acetaminophen, NSAIDs, gabapentin, carbamazepine SURGERY ▪ Correction of severe skeletal irregularities Figure 87.2 A section of a peripheral nerve from an individual with Charcot–Marie–Tooth disease. GUILLAIN–BARRÉ SYNDROME osms.it/guillain-barre-syndrome PATHOLOGY & CAUSES ▪ Acute, progressive demyelinating PNS disease; sensory, motor, cognitive deficits ▪ AKA acute inflammatory demyelinating polyneuropathy ▪ Abnormal autoimmune response ▫ Myelin autoantigen picked up by antigen-presenting cells (e.g. dendritic) → antigen presented to helper T-cells → production of cytokines → activation of B-cells and macrophages → B-cells make antibodies, mark autoantigens; macrophages use antibody markers to attack myelin sheath on peripheral neurons → ↓/blocked nerve conduction velocity; axonal degeneration 678 OSMOSIS.ORG Variants ▪ Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) ▪ Miller–Fisher syndrome ▫ Affects cranial nerves (CN) III, IV, VI ▪ Acute motor axonal neuropathy (AMAN) ▪ Acute sensorimotor axonal neuropathy (AMSAN) CAUSES ▪ Molecular mimicry between microbe, nerve antigens ▫ Most commonly associated with Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus, Epstein– Barr, influenza A, Zika, HIV
Chapter 87 PNS Demyelinating Disorders RISK FACTORS ▪ Acute infection ▪ ↑ age ▪ More common in individuals who are biologically male COMPLICATIONS ▪ Acute ▫ Ileus, urinary retention, cardiac arrhythmias, pneumonia, respiratory failure, quadriplegia ▪ Long-term ▫ Chronic fatigue, chronic pain, relapses SIGNS & SYMPTOMS ▪ Variable presentation, depending on affected nerve ▪ Bilateral, flaccid, ascending weakness of limbs, peaking ≤ four weeks ▪ ↓ deep tendon reflexes, areflexia, touch sensation ▪ Paresthesia ▪ Diaphragmatic weakness → breathing difficulties (e.g. hypoventilation, requires mechanical ventilation) ▪ Autonomic involvement ▫ Hypertension/hypotension/postural hypotension, bradycardia ▪ CN involvement ▫ Blurred vision, dysarthria, abnormal pupillary response to light DIAGNOSIS DIAGNOSTIC IMAGING Gadolinium-enhanced MRI (spine) ▪ T1-weighted images ▫ Thickening of intrathecal spinal nerve roots LAB RESULTS ▪ CSF ▫ Albuminocytologic dissociation (high levels of protein without increase in cell counts) ▪ Serum immunoglobulin G (IgG) antibodies to ganglioside Q1b (GQ1b) ▫ Miller–Fisher OTHER DIAGNOSTICS ▪ EMG, NCS ▫ ↓/blocked nerve conduction velocity ▪ History, physical examination TREATMENT MEDICATIONS ▪ IVIG ▪ Gabapentin/carbamazepine ▫ Pain management OTHER INTERVENTIONS ▪ Plasmapheresis ▪ Respiratory/hemodynamic support OSMOSIS.ORG 679

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of PNS Demyelinating Disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about PNS Demyelinating Disorders by visiting the associated Learn Page.