Nerve Conduction Velocity Factors: Myelination,

and Disorders of Myelination

 

I.          Nerve Conduction Velocity Factors

A.        Fiber diameter

1.         large fiber offers less resistance through its core so adjacent regions are brought to threshold faster (firing rate limiting factor = time to threshold)

2.         Farther current travels before charge diminishes, faster next segment will reach threshold

3.         ability of action potential to spread is proportional to amount of cytosol (smaller diameter = more membrane per segment, less cytosol)

4.         the closer to 1:1 (membrane to cytosol ratio), the faster is the conductance (due to resistance, capacitance, and other properties)

B.        Degree of myelination

1.         there are no ion channels beneath the myelin--no passive (leak) channels and no active (gated) channels at internode regions

2.         there ARE channels at the nodes (leads to the appearance of saltatory conduction)

3.         myelin increases resistance so charge less likely to spread in outward direction

4.         this has the effect of increasing the conduction velocity up to 100-fold.

 

II.          Because nerve fibers have different properties as a result of their conduction velocities, diameters, and other characteristics, they can be divided into three categories. A, B, and C (although some   

             sensory physiologists use Roman Numerals for the sensory fibers in the dorsal roots of spinal nerves).

              A.    Degree of myelination decreases as you move down this chart (e.g,Aα fibers are heavily myelinated whereas C fibers are unmyelinated).

              B.    Conduction velocity is directly related to degree of myelination.

 

III.         Disorders of Myelination

            A.        May involve white matter of the CNS or the PNS

                        1.         myelin is heavily proteinated and these proteins may be attacked by the immune system for various reasons or may be defective because of faulty genetic coding    

                                    (i.e., mutations)

                        2.         MS is considered a disorder of the CNS

3.         Guillain-Barre Syndrome (GBS) is considered a disorder of the PNS

B.        May be Demyelinating (e.g., MS) or dysmyelinating (Charcot-Marie-Tooth)

            C.        May be acquired or inherited

1.         Charcot-Marie-Tooth is inherited

2.         GBS is considered acquired (triggering event unknown, but probably due to presence of another pathogen, possibly viral)

            D.        Other causes of acquired demyelination

                        1.         radiation

                        2.         infarct

                        3.         tumors

                        4.         toxins or drugs

                        5.         infections

 

IV.        Select Disorders

            A.        MS

1.         etiology: usually autoimmune demyelinating disorder

a.         hypothetical causes: geographical (climate, seasonal changes), viral (direct or indirect), genetic (no gene located, concordance rate: 30%)

2.         mechanism:

§         Patches of inflammation occur in CNS

§         Inflammation results in edema

§         Inflammation and edema produce destruction of myelin

§         Glial cells begin remyelination

§         Remyelination may be insufficient or can produce scarring if repetitive

§         Demyelinated neuron is prone to axonal injury as well as disruption of AP transmission

§         Axonal injury can lead to degeneration of neuron, which will not be repaired

3.         Forms of MS

            a.         relapsing-remitting—most common (~60%)

            b.         primary progressive

            c.         secondary progressive

            d.         benign

4.         Symptoms:

§         Optic neuritis

§         Muscle weakness in limbs

§         Paresthesias

§         Bladder and bowel function disruption

§         Sexual difficulty

§         Fatigue

§         Cognitive-affective (depends on location of sclera, depression is common)

5.         Diagnostic tools: MRI, lumbar puncture, evoked potentials

                        6.         Treatment

                                    a.         treatment of course of disease: interferons

                                    b.         treatment of exacerbations: corticodsteroids

c.         treatment of symptoms: controlling environment (e.g., maintaining cool temps, cautious exercise, antispastic meds, external treatment of bladder and bowel problems or catheterization for bladder problems, counseling—family and patient)

B.        Guillain-Barre Syndrome

                        1.         Etiology

a.         typically follows a bacterial or viral infections (e.g., respiratory or GI)

b.         autoimmune disorder in which an attack is mounted against PNS

c.         possibly the immune system is confused by viral or bacterial antigens that are similar to proteins of the PNS

                        2.         Forms (types)

                                    a.         axonal (acute motor-sensory-axonal neuropathy)

                                    b.         demyelinating

                        3.         Symptoms

                                    a.         quick to appear, slower to disappear

                                    b.         initially weakness, progressing to full paralysis

c.         peak paralysis occurs within 2-3 weeks of initial symptoms

                        4.         Diagnosis

                                    a.         symptoms that fit the clinical picture

                                    b.         lumbar puncture

                                    c.         NCV

                        5.         Treatment

                                    a.         plasmaphoresis

                                    b.         immunoglobulin therapy

c.         maintaining cardiac and respiratory function (most important)

            C.        Leukodystrophies

                        1.        Overview

                                    a.        CNS vs PNS

                                    b.        examples

                       

            

Some Differences Among De- and Dysmyelinating Disorders

                         

CNS: White matter

 

PNS: Neuropathies

Demyelinating: primarily acquired.

MS, Progressive Multifocal Leukoencephalopahty (PML), Encephalomyelitis, Central Pontine Myelolysis (CPM), Anti-MAG Disease

Acquired: primarily autoimmune, demyelinating polyneuropathies.

Acute: Guillain-Barre Syndrome (GBS)

Chronic: Chronic Immune Demyelinating Polyneuropathy (CIDP), Anti-MAG Syndrome, Multiple Motor Neuropathy (MMN)

Dysmyelinating: Primarily inheritied

Leukodystrophies: Adrenoleukodystrophy (ALD), Alexander’s Disease, Canavan Disease, Krabbe Disease, Metachromatic Leukodystrophy (MLD), Pelizaeu-Merzbacher Disease, Refsum Disease, Cockayne Syndrome, Van der Knapp Syndrome,

Zellweger Syndrome

Hereditary: primarily dysmyelinating.

Hereditary Motor Sensory Neuropathies (HMSN), Charcot-Marie-Tooth (CMT), Cockayne Syndrome, Krabbe Disease, Metachromatic Leukodystrophy (MLD), Refsum Disease, Pelizaeus-Merzbacher Disease

Other causes of acquired demyelination in the CNS or PNS: radiation, infarct, tumors, toxins, drugs, infection