A 23-year-old woman is referred to a neurologist due to recent-onset diplopia and ataxia. She has not had similar symptoms before. However, about a year ago, she experienced numbness and paresthesia involving her left leg that have since resolved. After a comprehensive neurological examination, the physician orders an MRI of the brain, which reveals several areas of T2 hyperintensity consistent with axonal demyelination. A diagnosis of multiple sclerosis is made. Which of the following neuronal properties is most likely to decrease as a direct result of demyelination?

Question

A 23-year-old woman is referred to a neurologist due to recent-onset diplopia and ataxia.  She has not had similar symptoms before.  However, about a year ago, she experienced numbness and paresthesia involving her left leg that have since resolved.  After a comprehensive neurological examination, the physician orders an MRI of the brain, which reveals several areas of T2 hyperintensity consistent with axonal demyelination.  A diagnosis of multiple sclerosis is made.  Which of the following neuronal properties is most likely to decrease as a direct result of demyelination?

Quizplus · Accepted Answer

Multiple sclerosis is an immune-mediated demyelinating disease of the central nervous system. Myelin is an electrical insulator and increases the conduction velocity of action potentials; demyelination leads to slowing of the impulses with resultant neurological deficits. The speed of conduction down an axon depends on 2 constants: the length constant and the time constant (ie, velocity = length/time). The length constant, also known as the space constant, is a measure of how far along an axon an electrical impulse can propagate without requiring active regeneration by ion channels. It is based on the relative resistance of conduction along the axon (within the cytoplasm) compared to the resistance across the membrane. Myelin increases the length constant by reducing charge dissipation across the membrane (increasing membrane resistance). This allows the electrical impulse from individual sodium channels to travel farther, allowing activation of more distant channels. As such, demyelination will decrease the length constant and result in shorter impulse conduction. The time constant is a measure of the time it takes for the membrane potential to respond to a change in membrane permeability (ie, sodium channel activation) and is based on membrane resistance and capacitance. Myelin decreases membrane capacitance (reduces the amount of charge stored by the membrane) and increases membrane resistance (reduces charge leakage through the membrane) in axon segments between the nodes of Ranvier; this reduces the time constant and allows the membrane potential to change faster. Demyelination would increase the time constant and result in slower changes in membrane voltage. Therefore, demyelination decreases neuronal signaling velocity both by decreasing the length constant and increasing the time constant (ie, ↓ velocity = ↓ length / ↑ time) (Choice E). (Choices B and C) Summation refers to the additive effects of multiple postsynaptic potentials on a target neuron's membrane potential. Summation can occur in the dendrites, cell body, and axon hillock but not in the axon. Temporal summation refers to the combined effect of sequential impulses from the same neuron over time, whereas spatial summation refers to the combined effect of simultaneous impulses from several different neurons. (Choice D) Threshold refers to the membrane potential value required to initiate an action potential. It is determined by the intrinsic properties of the voltage-gated sodium channels present in the membrane. Educational objective: The speed of conduction down an axon depends on 2 constants: the length constant and the time constant (ie, velocity = length/time). Myelination increases the length constant and decreases the time constant, both of which improve axonal conduction speed. Demyelination thus impairs stimulus transmission. __________ References: Multiple sclerosis: the disease and its manifestations. (http://www.ncbi.nlm.nih.gov/pubmed/10603614) The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. (http://www.ncbi.nlm.nih.gov/pubmed/10603618)

A 23-Year-Old Woman Is Referred to a Neurologist Due to Recent-Onset