Preheat oven to 400° Fahrenheit. Spray the bottom of a 9x13 baking dish with non stick cooking spray.
In a large pot of well-salted, boiling water, cook pasta to al dente according package directions. Drain & rinse pasta. Return pasta to pot and set aside.
In a large skillet, melt 2 tablespoons of butter, sautee onion and garlic for 1-2 minutes over medium-high heat. Add crab, shrimp and 1 teaspoon of Creole seasoning and cook just until shrimp is pink. Remove from heat. Add seafood mixture to pasta and toss.
Return skillet to stove top. Over medium heat, melt 4 tablespoons of butter. Whisk in flour, whisking & cooking for one minute until smooth. Whisk in 3 cups of milk a little at a time, making sure roux is smooth before adding more. Whisk in last teaspoon of Creole seasoning.
Add half of the cheddar cheese. Whisk until melted. Add half of the Gruyere, whisking until melted. Remove from heat, add cream cheese, whisking until mostly melted. Taste sauce. Adjust seasonings as needed with salt, black pepper or cayenne as this will be the flavor of your mac and cheese.
Pour sauce over pasta and seafood, using a rubber spatula to get all of the sauce from the skillet. Toss to completely coat pasta and seafood. Add last cup of milk and toss again.
Spoon ½ of the pasta mixture in bottom of the 9x13 dish. Top with ½ of remaining cheddar and Gruyere. Layer rest of pasta on top of cheeses. Top with rest of cheeses. Cover evenly with panko bread crumbs. Melt last 2 tablespoons of butter. Drizzle over the top of the macaroni and cheese casserole.
Bake in preheated oven for 20-25 minutes or until the panko topping is golden brown and edges are bubbly. Remove from oven and let sit for 5-10 minutes before serving. Garnish with chopped parsley for color, if you like.