Traditional understanding has MS starting in the white matter of the brain, in other words in the inside layers. A new study by Dr. Lucchinetti, posted on the MayoClinic blog purports the opposite: The outer layers of the brain would be affected first, then the inner layers. Research was conducted by Richard Ransohoff and Claudia Lucchinetti
Inward or outward progression, matters to target drugs in the early stages of the disease. Also important is the confirmation of MS as an inflammatory process
This what Dr Luchinetti says:
“…the early lesions were highly inflammatory. These findings were reassuring because they indicated that treatments targeting inflammation in the disease may ameliorate MS effects on both the cortex as well as the white matter...”
Here is a clear sketch of the human brain according to Korbinian Broadmann, an early German neurologist
As for their respective function, let us say in a nutshell, that the Cortex has sensory and motor areas, whereas the white matter is more involved in transmission of signal 
So inflammation would be the source of much of Multiple Sclerosis. An example of how inflammation can affect the Central Nervous System can be found in a study  of inflammatory signals that affect the central Nervous system. Quoting:
“…Interleukin.. dependent … T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity…”
This recent result is really part of a controversy: Several previous studies really present a more nuanced perspective where inflammation and neurodegeneration are associated.
Take for example the study published in Brain, an Oxford Journal . That study even though claiming to associate both findings of inflammation and neurodegeneration in autopsied brains of MS patients, discusses mostly the inflammation aspects. On neurodegeration the findings are more muted. Quoting:
‘..A highly significant association between inflammation and axonal injury was seen in the global multiple sclerosis population as well as in progressive multiple sclerosis alone…”
Axonal injury is an injury to the nerve connection which carry the nervous signal. See sketch below from Wikipedia:
Another study associating both inflammation and neurodegeneration was presented in . Quoting them:
“…. Neuronal loss was observed both in Deep Gray Matter (DGM) lesions and nondemyelinated DGM with neuron atrophy in nondemyelinated DGM...”
So is the popular concept of MS being a disease primarily caused by demyelination too simplistic?
It is not clear,though, that the axon damage could not caused directly by an inflammation, without a specific degenerative process…
Note: Inflammation diseases should be distinguished from neurodegenerative diseases like Alzheimer’s , Parkinson’s, and ALS. In this class of neurological disease a substance, usually a protein is over or under produced : A-beta and tau brain proteins loosing its correct shape (misfolding) for Alzheimer’s; Dopamine under-produced for Parkinson’s. The protein can also subject to a mutation (Huntington’s).
Is this a case of which comes first : the chicken or the egg?
Talk to your Doctor
 MarketWatch: MayoClinic; Press Release ; “From the Outside In: Mayo Clinic Collaboration Finds Multiple Sclerosis Often Starts in Brain’s Outer Layers” ; Dec 07, 2011
 Wikipedia, Neurodegenerative disorders
 Journal of Experimental Medicine; “IL-23 drives a pathogenic T cell population that induces autoimmune inflammation” ; 2005 January 17;
 Brain ; “The relation between inflammation and neurodegeneration in multiple sclerosis brains”; February 27, 2009.
 J Neuropathol Exp Neurol. ; ”Demyelination, inflammation, and neurodegeneration in multiple sclerosis deep gray matter.” 2009 May