You can feel isolated, even if surrounded by many. Samantha never felt welcome in the small town where she went to college. However, that changed slightly the day she met him. She welcomed him when no one else did. She stood by him even if others did not for his quirks. She knew how loneliness could tear someone apart. Samantha did not mind Michael's strangeness and uniqueness.
That's why it hurt so much when he began to act differently... so very different.