Scoring for Multiple Sclerosis Studies
Scoring Disease Markers in the EAE Model of Multiple Sclerosis
In the development of new drugs for multiple sclerosis, scoring systems play a vital role in providing measurable endpoints that inform researchers about treatment efficacy and disease progression. Inotiv scientists utilize clinical, inflammation, and demyelination scores to gather objective data from the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis that guides decision-making throughout the drug development process. These scores not only facilitate the evaluation of new therapeutic approaches but also help in understanding the complex nature of multiple sclerosis, ensuring that drug candidates are effective.
Clinical Scoring of EAE Model
Clinical scores focus on evaluating the severity of symptoms in the EAE model of multiple sclerosis. These scores are valuable for understanding disease pathogenesis and assessing the efficacy of new therapeutic agents.
| Score | Clinical Observations |
| 0 | No motor function changes compared to non-immunized mice. When picked up by the tail, it is tense and erect. Hind legs are spread. No gait or head tilting when walking. |
| 0.5 | Tip of tail is limp. When picked up, it has tension except at the tip. Muscle straining is felt, and the tail moves. |
| 1 | Limp tail. When picked up by the base, it drapes over the finger. Hind legs are spread. No tail movement observed. |
| 1.5 | Limp tail and hind leg issues. Picked up by the base, the tail drapes over the finger. On a wire rack, one hind leg falls through. Walking is slightly wobbly. |
| 2 | Limp tail and weak hind legs. Picked up by the base, legs are held close. Walking is wobbly with one foot dragging. Other leg moves normally. - OR - Mouse scores 0.0 but shows head tilting and poor balance. |
| 2.5 | Limp tail and dragging hind legs. Both legs drag, tripping the mouse. - OR - One leg drags completely, the other moves. - OR - Mild EAE (score 0.0-1.5) but strong head tilt causes falls. |
| 3 | Limp tail and hind leg paralysis. - OR - Limp tail, hind legs can paddle but not move forward. - OR - Limp tail, one front and one hind leg paralyzed. - OR - Severe head tilt, edge-walking, pushing cage wall, spinning when picked up. |
| 3.5 | Limp tail, hind leg paralysis. Moves in cage but can't right itself when on side; hind legs together on one side. - OR - Moves in cage, hindquarters flat, front appears humped. |
| 4 | Limp tail, hind leg and partial front leg paralysis. Mouse moves minimally but is alert and feeding. Euthanasia is recommended after a 4.0 score for 2 days. With daily SC fluids, some recover to 3.5 or 3.0. A score of 5.0 is recorded for euthanized mice due to severe paralysis. |
| 4.5 | Complete hind, partial front leg paralysis, no movement in cage. Mouse unresponsive, minimal front leg movement. Euthanasia recommended. Score 5.0 after euthanasia for experiment. |
| 5 | Mouse rolling in cage (euthanasia recommended). - OR - Mouse found dead from paralysis. - OR - Mouse euthanized due to severe paralysis. |
Scoring CNS Inflammation in EAE Model
Inflammation scores are essential in multiple sclerosis research, quantifying inflammatory markers in the central nervous system (CNS) to reflect immune system activity. Elevated scores indicate active inflammation, allowing researchers to evaluate the anti-inflammatory effects of therapies and their potential to halt disease progression.
| Score | Inflammatory Observations |
| 0 | No inflammation. |
| 0.5 | Very minimal inflammation, with very small foci or few inflammatory cells. Less than 1% of grey or white matter, or length of meninges affected. |
| 1 | Minimal inflammation, with a few scattered inflammatory cells. 2-10% of grey or white matter, or length of meninges affected. |
| 2 | Mild inflammation, with perivascular cuffing with inflammatory cells. 11-25% of grey or white matter, or length of meninges affected. |
| 3 | Moderate inflammation, with more extensive perivascular cuffing and beginning parenchymal infiltration. 26-50% of grey or white matter, or length of meninges affected. |
| 4 | Marked inflammation, with widespread perivascular cuffing and significant parenchymal infiltration. 51-75% of grey or white matter, or length of meninges affected. |
| 5 | Severe inflammation, with extensive infiltration throughout the spinal cord with substantial tissue damage. Greater than 75% of grey or white matter, or length of meninges affected. |
Scoring CNS Demyelination in EAE Model
Demyelination scores assess the extent of damage to the myelin sheath surrounding nerve fibers, a critical feature of multiple sclerosis. This scoring provides insights into the degree of neurological impairment and helps identify the effectiveness of therapies aimed at repairing or protecting myelin.
| Score | Demyelination Observations |
| 0 | No demyelination. |
| 0.5 | Very minimal demyelination. Few scattered affected axons in less than 1% of the white matter. |
| 1 | Minimal demyelination with small, focal areas of myelin loss. 2 -10% of the white matter affected. |
| 2 | Mild demyelination with larger areas of myelin loss but still limited in extent. 11-25% of the white matter affected. |
| 3 | Moderate demyelination with multiple or more extensive areas of myelin loss. 26-50% of the white matter affected. |
| 4 | Severe demyelination with widespread and extensive myelin loss throughout large areas of the spinal cord. 51-75% of the white matter affected. |
| 5 | Very severe demyelination with nearly complete or complete loss of myelin in large regions of the spinal cord. Greater than 75% of the white matter affected. |
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