Cognitive issues, colloquially known as ‘Brain Fog’, are a common complaint of people with MS, with an estimated 70% of people progressing to report problems with thinking, concentration or memory.
A recent study published in the Journal of Neuroscience sheds new light on damage caused by MS, specifically in the brain, which may help to explain this cognitive decline and consequently help researchers to target effective treatments. Lead author of the study, neurologist Matthew Bellizzi, notes that the research identifies a new disease mechanism in MS which causes damage to neurons independent of the demyelination which normally characterises the disease.
This, he explains, represents a further component of the disease and importantly, is one that is not prevented or controlled by the current range of disease-modifying immunosuppressive drugs used to treat MS. The drugs which are currently at the disposal of physicians are effective in suppressing the attacks which lead to myelin damage, however they are ineffective in the prevention of cognitive issues.
Hence, researchers speculate that there may be additional, as yet not fully understood, damage occurring in the central nervous system. Senior author of the study, Harris Gelbard, feels that for too long MS has largely been discussed as a disease which affects sensory or motor functions, yet for many patients it is the loss of cognitive ability which has the greatest impact on their quality of life.
The research team carried out experiments in mouse models of MS, and showed that neurons in the hippocampus (an area of the brain not associated with motor control) were being damaged at the synapse, which is the point where cells communicate with each other via the transmission of chemical signals.
And, responsible for this damage they report, appears to be the microglia - a cell in the central nervous system’s defences. The primary role of the microglia is to fight infection or other attacks on the nervous system, and to clean up the damaged cells, but it also serves to preserve the health of the synapse so that it functions normally and aids the hippocampus with cognitive abilities such as learning and memory.
The problems therefore occur when the immune system is over-stimulated during MS, and the microglia receive distress signals which prompt them to switch from their protective, nurturing role to an aggressive, pro-inflammatory response. During this reaction, they release the molecule PAF (platelet-activating factor), which affects the signalling that neurons use to activate one another.
High levels of PAF cause over-activation of these signals and actually serve to destroy the receiving end of the synapse. Consequently, more microglia and other immune cells rush to the site, which triggers a cycle of destruction.
The researchers felt that the cumulative effect was like trying to put out a fire with gasoline. It is this phenomenon which the researchers believe is largely responsible for the greater part of the cognitive damage and over-time decline that people with MS experience.
Due to the activation of microglia being unaffected by current MS drugs, research is now focusing on potential therapies which could suppress the signalling pathways which result in nerve cells and microglia becoming overactive.
Amongst the potential candidates is a drug which is being investigated in the treatment of HIV-associated neurological disorders.
It is interesting to note of course that the OMS Recovery Program works precisely through this mechanism of switching the immune system from an over-stimulated mode (Th1 response) to a more quiescent mode (Th2 response); there is every likelihood that this helps to put out the fire around the synapses in the central nervous system.