Physiology · Year 1 · from Physiology
Case 1: Multiple Sclerosis - Central Demyelination
Clinical Image
Source: Wikimedia Commons - MS Demyelination - CC BY-SA 3.0
Patient Presentation
A 28-year-old female presents to the neurology clinic with a 3-week history of blurred vision in her right eye that has progressively worsened. She describes pain with eye movement. She also reports an episode 6 months ago of numbness and tingling in her legs that resolved after several weeks without treatment. She noticed that her symptoms seemed worse after taking a hot shower or exercising (Uhthoff phenomenon).
Demographics
- Age: 28 years
- Sex: Female
- Ethnicity: Northern European descent
Chief Complaint
Progressive blurred vision in right eye with pain on eye movement
Physical Examination
- Visual acuity: Right eye 20/100, Left eye 20/20
- Fundoscopy: Right optic disc pallor, normal left eye
- Pupillary exam: Right relative afferent pupillary defect (RAPD/Marcus Gunn pupil)
- Color vision: Impaired red desaturation in right eye
- Neurological: Brisk reflexes in lower extremities, positive Babinski sign bilaterally
- Sensory: Mild decreased vibration sense in feet
- Lhermitte sign: Positive (electric shock sensation down spine with neck flexion)
Workup
- MRI brain with contrast: Multiple periventricular white matter lesions, some enhancing with gadolinium (indicating active inflammation), Dawson fingers pattern
- MRI spine: Two demyelinating lesions in cervical spinal cord
- Visual evoked potentials (VEP): Prolonged P100 latency in right eye (delayed conduction)
- Lumbar puncture: Oligoclonal bands present in CSF (not in serum), elevated IgG index
- Serum studies: Negative for NMO-IgG antibodies
Diagnosis
Relapsing-remitting Multiple Sclerosis (RRMS) with optic neuritis, meeting McDonald criteria for dissemination in space and time
Treatment
- Acute episode: IV methylprednisolone 1g daily for 3-5 days (hastens recovery, does not change long-term outcome)
- Disease-modifying therapy: Initiate high-efficacy DMT (e.g., ocrelizumab, natalizumab, or fumarates)
- Symptomatic treatment for spasticity, fatigue, and neuropathic pain as needed
- Physical therapy and rehabilitation
- Regular MRI monitoring for new lesion activity
- Vitamin D supplementation
- Counseling regarding prognosis and disease management
Physiological Principles Demonstrated
- Saltatory conduction: In myelinated axons, action potentials "jump" from one node of Ranvier to the next, dramatically increasing conduction velocity (up to 120 m/s vs. 0.5-2 m/s in unmyelinated fibers).
- Myelin function: Myelin acts as an electrical insulator, increasing membrane resistance and decreasing capacitance, allowing current to flow efficiently to distant nodes.
- Demyelination effects: Loss of myelin exposes the axon membrane, causing current leakage, slowed conduction velocity, and eventually conduction block when the current reaching the next node is insufficient to reach threshold.
- Temperature sensitivity (Uhthoff phenomenon): Heat worsens conduction in demyelinated fibers. Elevated temperature increases potassium channel activity and decreases sodium channel availability, widening the safety factor gap in already compromised axons.
- Visual evoked potentials: The prolonged P100 latency directly measures slowed conduction velocity in the optic nerve due to demyelination.
- Length constant: Demyelination decreases the length constant (the distance over which a signal decays to 37% of its original value), impairing the ability of local currents to depolarize distant membrane segments.