Overview
This lecture covers cortical spreading depression (CSD), focusing on its role in migraine, the neurophysiology behind it, associated symptoms, and its distinction from normal neuronal signaling.
Cortical Spreading Depression & Migraine
- CSD is a wave of neuronal and glial depolarization linked to migraine, especially the aura phase.
- Typical aura symptoms are visual, sensory, and speech/language disturbances, usually in that order.
- Non-typical aura symptoms include motor (hemiplegic migraine), brainstem, and retinal disturbances, each with their own diagnoses.
- CSD triggers activation of the trigeminovascular system, leading to migraine pain and changes in cerebrospinal fluid (CSF), such as increased CGRP protein.
Anatomy & Initiation of CSD
- "Cortical" refers to the cerebral cortex, the brain's outer gray matter layer.
- CSD almost always starts in the occipital lobe (visual cortex), due to its high neuronal density.
- The wave travels posterior-to-anterior: occipital (visual aura), parietal (sensory aura), temporal/frontal (language aura), then frontal (motor aura in some cases).
- Both neurons and glial (especially astrocyte) cells are affected during CSD.
Comparison: CSD vs. Action Potential
- Action potential is a rapid, localized electrical signal in neurons, all-or-nothing, with quick depolarization to +40 mV.
- CSD is a slow, spreading depolarization to 0 mV over minutes, affecting large cortical areas.
- CSD is triggered by factors like increased extracellular potassium or intense neuronal activity, overwhelming normal regulation.
- Recovery from CSD is slow and requires much energy (up to 250% increase in glucose use).
Mechanism & Symptoms
- CSD causes prolonged depolarization followed by a period of "depression," where brain regions are temporarily inactive.
- Symptoms reflect the affected cortical area: visual symptoms (occipital), sensory (parietal), language (temporal/frontal), motor (frontal).
- Non-typical aura symptoms occur if non-standard areas are involved (e.g., brainstem, retina).
- The depression phase may protect the brain by shutting down hyperactive regions and allowing metabolic recovery.
Additional Effects & Clinical Implications
- CSD causes blood flow changes: an initial brief increase (hyperemia) followed by prolonged decrease.
- There is increased oxidative stress and production of reactive oxygen species.
- CSD may underlie premonitory (prodrome) symptoms, headache, and postdrome stages of migraine.
- Affected regions can explain symptoms like yawning, food cravings, photophobia, phonophobia, and dizziness.
Key Terms & Definitions
- Cortical Spreading Depression (CSD) — Wave of depolarization moving across cerebral cortex, underlying migraine aura and pain.
- Aura — Sensory or neurological symptoms preceding or accompanying migraine.
- Depolarization — Loss of difference in charge across neuron membrane, enabling signal conduction.
- Gray Matter — Brain tissue rich in neuronal cell bodies.
- Trigeminovascular System — Neural pathway implicated in migraine pain signaling.
- CGRP — Calcitonin gene-related peptide, a protein linked to migraine.
Action Items / Next Steps
- Review the functions of different brain lobes closely to understand aura symptom mapping.
- Memorize the order and characteristics of typical vs. non-typical aura symptoms.
- Study the differences between action potentials and CSD for exam questions.