Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

Evonuk, Kirsten S.; Moseley, Carson E.; Doyle, Ryan E.; Weaver, Casey T.; DeSilva, Tara M.

Relevant clinical assessments are made according to the following rubric for typical ( Figure 1C ) or atypical (Figure 1D ) EAE. For typical clinical disease, a score of 0 is no abnormal behavior. When picked up by the base of the tail, the tail may rotate quickly (much like a helicopter rotor) and the hind legs will spread apart. A clinical score of 1 is a partially limp tail, which may be determined by lifting the mouse by the base of the tail. The normal helicopter-like rotating may be weakened or absent, and part of the tail may be completely limp. A helpful way to determine extent of tail paralysis is to run one's finger up the length of the tail, as an unparalyzed tail will usually curl around the finger while a partially paralyzed tail will be unable to do so. A clinical score of 2 represents a completely paralyzed tail. No movement of the tail occurs at all when picking the mouse up at the base of the tail. A clinical score of 3 represents partial hind limb paralysis. Determination of this score requires that the mouse be free to move on a flat surface. If one hind limb is dragging as the mouse moves forward, or if one or both hind limbs appear to be partially paralyzed, a score of 3 may be given. A clinical score of 4 represents complete hind limb paralysis. With this score, a mouse will be unable to move its hind limbs and will drag itself forward using its front limbs. A clinical score of 5 represents a moribund mouse, or a mouse with difficulty moving itself across its cage or breathing. If a mouse cannot drag itself along the bottom of the cage or if its breathing is labored, the Atypical clinical disease may or may not be accompanied by paralysis. It may be necessary to include two separate scoring systems if a mouse presents with atypical disease plus typical symptoms. A score of 0 is no abnormal behavior, as with the typical scoring system. A clinical score of 1 represents a slight head turn or tilt while the mouse is walking. This may be determined by allowing the mouse to walk forward and observing a constant left or right directionality to its movement. A clinical score of 2 represents a more pronounced head turn and poor righting ability. As with an atypical score of 1, the mouse has directionality to its movement and may have slight difficulty with balance. A clinical score of 3 represents an inability to walk in a straight line. The mouse will have difficulty balancing and may use the side of the cage to help right itself as it walks. A clinical score of 4 represents a mouse laying on its side, unable to walk due to balancing issues. The mouse may be able to drag itself along the bottom of the cage but may have directionality to its movement. A clinical score of 5 represents continuous rolling unless supported. A mouse that reaches this score should be humanely euthanized. A clinical score of 6 represents a mouse found dead in its cage. A score of 6 is unusual and causes of death other than EAE should be investigated.