PNS Demyelinating Disorders Notes

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