Background
One of the major causes of disability in primary progressive MS (PPMS) is ongoing neurodegeneration of the brain and spinal cord. Developing the tools and technologies to visualize and measure progressive neurodegeneration is, therefore, essential to managing MS. These tools can give us a better understanding of why neurodegeneration occurs, why it leads to disability, how it can be treated and whether the treatment was effective.
Recent developments in magnetic resonance imaging (MRI) technology have proven particularly effective at gauging neurodegeneration in MS. For example, advanced MRI techniques can inform researchers and clinicians as to the amount of certain chemicals in a person’s brain. This is important in terms of neurodegeneration, as each chemical tells a story about the health of a nerve cell. At the same time, more sensitive and objective clinical measures are also needed to reflect how nerve cell damage translates into disability. Now, for the first time, a team of researchers from the United Kingdom – including Dr. Olga Ciccarelli and Dr. Alan Thompson – has combined advanced MRI techniques with sensitive clinical measures to detect early signs of neurodegeneration in the spinal cords of persons with PPMS. Their findings were published in the journal Brain.
The Study
The researchers enrolled 21 individuals with relatively early PPMS (diagnosed no more than 6 years prior) and 24 non-MS individuals. They analyzed and compared the upper spinal cords of all participants, first using basic MRI – which provides a visual image of the spinal cord – and then by using two advanced MRI techniques; magnetic resonance spectroscopy and q-space imaging.
Magnetic resonance spectroscopy was used to measure the concentration of various chemicals in the spinal cord. Each chemical provides the researchers with a readout of the spinal cord’s overall neural health. The second technique, q-space imaging, helped to measure the movement (or diffusion) of water molecules in the myelin surrounding nerve fibres in the spinal cord. Measuring the diffusion of water molecules can help map out the structure of cells in the myelin and detect tissue damage and degeneration.
The researchers compared their advanced MRI findings to disability scores in the PPMS participant group. Because of their spinal cord focus, the research team relied on both conventional disability tests (such as the Expanded Disability Severity Scale, EDSS) as well as less commonly used disability scales that are more sensitive to spinal cord damage. These included tests for grip strength, ability to maintain posture and ability to perceive vibrations.
Results
Individuals with early PPMS did not appear to have spinal cord atrophy (atrophy, or shrinking, is a sign of widespread demyelination and/or neurodegeneration due to tissue loss) relative to non-MS individuals. On the other hand, the concentrations of chemicals that indicate healthy nerve cells were lower in the spinal cords of persons with PPMS compared to healthy controls. As well, water diffusion was increased in participants with early PPMS, indicating that myelin and/or nerve fibres had undergone damage.
Within the PPMS group itself, individuals with higher disability scores also tended to have lower concentrations of chemicals indicating nerve cell health, along with increased water diffusion in their spinal cord.
Comment
Drs. Ciccarelli, Thompson and colleagues were able to demonstrate that, even in the absence of atrophy, the spinal cords of individuals with early PPMS had clear indications of nerve cell and/or myelin degeneration. Furthermore, the study made an important link showing that, in the authors words, “early spinal neurodegeneration may underlie clinical impairment” in PPMS. That the damage was only seen through the use of advanced MRI techniques showcases the sensitivity of this technology and the need to push for continued technological advances.
By identifying early and subtle forms of spinal cord damage, clinicians will be better equipped to pre-empt degeneration through the early use of neuroprotective therapies that are currently under development or being evaluated in clinical trials (see Treatments in Development for more details). Using advanced MRI monitoring, researchers and clinicians will also be able to measure the outcomes of treatment in ways that were simply not possible in the past, picking-up even minor alterations to the spinal cord’s overall health. The goal is for strategies like these to fill the gap in treatment and monitoring options for people living with both forms of progressive MS.
Source
Abdel-Aziz K et al. (2015). Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis. Brain. 138(Pt 6):1568-82.