In the context of patients with the spinal onset of ALS, the increase of CSF total proteins and QAlb may be related with the loss of BBB integrity that allows infiltration into the CNS of the cytokines, chemokines, and other proinflammatory mediators, and of peripheral leukocytes such as monocytes, macrophages and CD4 T cells that may interact with activated astrocytes and microglia, leading to accelerated disease progression [41,43,44,45,46]. Here, CD4 is linked to amyotrophic lateral sclerosis.