JNS-13414; No of Pages 2 Journal of the Neurological Sciences xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Editorial
Utilization of brain MRI with focus on cerebral lesions and atrophy to better characterize MS phenotypes A R T IC L E
IN F O
Article history: Received 27 August 2014 Accepted 29 August 2014 Available online xxxx Keywords: MRI Phenotype Clinical course Atrophy Lesion volume Multiple sclerosis
Multiple sclerosis (MS) is presumably an immune-mediated and degenerative disease of human central nervous system, which usually affects the younger individuals and leads to permanent disability. While the cause and cure for MS remain unrecognized, many neurologists and neuroscientists attempt to explain the diverse nature of its clinical presentations and natural history by establishing clinical classifications. The present classification of MS into four main clinical types is far from perfect and has left the clinicians with many unanswered questions. The article by Tauhid et al. provides an excellent discussion of the continuing efforts to explain the heterogeneous nature of current multiple sclerosis (MS) subtypes. While patients with MS are typically assigned to one of the disease categories in an effort to provide a clear clinical definition of their disease progression and status, much heterogeneity exists within the subtypes, making it difficult to fully and accurately reflect a patient's current state of disease in terms of cerebral atrophy and lesion volume. The authors recognized this ongoing problem and sought to establish a neuroimaging categorization system for MS phenotypes based on lesion severity (T2LV) and cerebral atrophy (brain parenchymal fraction [BPF]). Using these MRI variables and stratifying the 175 patients in the study by median splits, four categories were established to represent patients with the presence of mild atrophy and low T2LV (Type 1); mild atrophy and high T2LV (Type 2); high atrophy and low T2LV (Type III); and high atrophy and high T2LV (Type IV) [1]. The authors should be commended for their approach to addressing this complicated diagnostic issue. The fundamental methodology used to establish the categories have the potential to be used to provide an objective standardized categorization system for our MS population on a global level. In the past, several attempts have been made to develop such a systematic approach to MS subtyping,
all of which, as with the current study, have maintained a degree of uncertainly it their applicability to clinical practice pending further research and additional considerations in terms of methodology, pathogenesis issues, clinical questions, the role of atrophy in prognosis, treatment monitoring, and expanded collaborative work across sites and increased patient sample sizes [1–3]. What the present study offers is a comprehensive review of a generous sample using a retrospective, cross-sectional design to examine the progression of multiple sclerosis across time, as the range of disease onset ranged from around 3 months to four years. While, ideally, a prospective research design would capture disease progression across time, the authors have done an excellent job including patients in their sample representing virtually all stages of disease progression, which both strengthens and validates their findings. These study results clearly indicate variability among standard MS classifications as well as within disease categories, as represented by the finding that the Type IV phenotype representing both highest atrophy and lesion volume was comprised of 50% secondary progressive MS diagnosed patients and 50% relapsing–remitting MS [1]. Disease progression under current clinical reasoning would expect to see a higher percentage of patients with secondary progressive MS in this highest level of disease state. This finding, coupled with other results, such as an unexpected split of patients diagnosed with clinically isolated syndrome between Type I and Type III phenotypes, warrants further investigation and raises the question whether the true clinical picture as evidenced by T2LV and cerebral atrophy should be used for diagnostic purposes initially. One could argue that the presence of the highest levels of atrophy would be seen in those patients with the longest history of disease and would be expected to fall into either phenotype III or IV. However, the results of this study defy that logic as evidenced by the presence of 19% of the secondary progressive MS diagnosed patients falling under Type I and Type II and having only mild atrophy. Were these patients misdiagnosed with the current subtype or does the variability within the subtype represent an opportunity to expand the disease categories to include a place for those patients who do not follow traditional diagnostic principles? To answer these and other questions raised by the significant findings of this research, further studies utilizing an objective MS population-based median of the neuroimaging parameters presented here could be used as the reference point for calculating median splits as opposed to a stratification of a cross-sectional single institution study sample. Using the same methodological approach on a national average scale could potentially offer additional insight into the etiology of heterogeneity seen both among and within traditionally applied MS classifications.
http://dx.doi.org/10.1016/j.jns.2014.08.046 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: McGee J, Minagar A, Utilization of brain MRI with focus on cerebral lesions and atrophy to better characterize MS phenotypes, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.08.046
2
Editorial
Conflict of interest We wish to confirm that there are no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. References [1] Tauhid S, Neema M, Healy BC, Weiner HL, Bakshi R. MRI phenotypes based on cerebral lesions and atrophy in patients with multiple sclerosis. J Neurol Sci 2014. [2] Luo J, Yablonskiy DA, Hildebolt CF, Lancia S, Cross AH. Gradient echo magnetic resonance imaging correlates with clinical measures and allows visualization of veins within multiple sclerosis lesions. Mult Scler J 2014;20(3):349–55.
[3] Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, et al. Evidence of a two-stage disability progression in multiple sclerosis. Brain 2010;133:1900–13.
Jeanie McGee Alireza Minagar Department of Neurology, Louisiana State University Health Sciences Center — Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA E-mail address: [email protected] (A. Minagar). 27 August 2014 Available online xxxx
Please cite this article as: McGee J, Minagar A, Utilization of brain MRI with focus on cerebral lesions and atrophy to better characterize MS phenotypes, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.08.046
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Editorial
Utilization of brain MRI with focus on cerebral lesions and atrophy to better characterize MS phenotypes A R T IC L E
IN F O
Article history: Received 27 August 2014 Accepted 29 August 2014 Available online xxxx Keywords: MRI Phenotype Clinical course Atrophy Lesion volume Multiple sclerosis
Multiple sclerosis (MS) is presumably an immune-mediated and degenerative disease of human central nervous system, which usually affects the younger individuals and leads to permanent disability. While the cause and cure for MS remain unrecognized, many neurologists and neuroscientists attempt to explain the diverse nature of its clinical presentations and natural history by establishing clinical classifications. The present classification of MS into four main clinical types is far from perfect and has left the clinicians with many unanswered questions. The article by Tauhid et al. provides an excellent discussion of the continuing efforts to explain the heterogeneous nature of current multiple sclerosis (MS) subtypes. While patients with MS are typically assigned to one of the disease categories in an effort to provide a clear clinical definition of their disease progression and status, much heterogeneity exists within the subtypes, making it difficult to fully and accurately reflect a patient's current state of disease in terms of cerebral atrophy and lesion volume. The authors recognized this ongoing problem and sought to establish a neuroimaging categorization system for MS phenotypes based on lesion severity (T2LV) and cerebral atrophy (brain parenchymal fraction [BPF]). Using these MRI variables and stratifying the 175 patients in the study by median splits, four categories were established to represent patients with the presence of mild atrophy and low T2LV (Type 1); mild atrophy and high T2LV (Type 2); high atrophy and low T2LV (Type III); and high atrophy and high T2LV (Type IV) [1]. The authors should be commended for their approach to addressing this complicated diagnostic issue. The fundamental methodology used to establish the categories have the potential to be used to provide an objective standardized categorization system for our MS population on a global level. In the past, several attempts have been made to develop such a systematic approach to MS subtyping,
all of which, as with the current study, have maintained a degree of uncertainly it their applicability to clinical practice pending further research and additional considerations in terms of methodology, pathogenesis issues, clinical questions, the role of atrophy in prognosis, treatment monitoring, and expanded collaborative work across sites and increased patient sample sizes [1–3]. What the present study offers is a comprehensive review of a generous sample using a retrospective, cross-sectional design to examine the progression of multiple sclerosis across time, as the range of disease onset ranged from around 3 months to four years. While, ideally, a prospective research design would capture disease progression across time, the authors have done an excellent job including patients in their sample representing virtually all stages of disease progression, which both strengthens and validates their findings. These study results clearly indicate variability among standard MS classifications as well as within disease categories, as represented by the finding that the Type IV phenotype representing both highest atrophy and lesion volume was comprised of 50% secondary progressive MS diagnosed patients and 50% relapsing–remitting MS [1]. Disease progression under current clinical reasoning would expect to see a higher percentage of patients with secondary progressive MS in this highest level of disease state. This finding, coupled with other results, such as an unexpected split of patients diagnosed with clinically isolated syndrome between Type I and Type III phenotypes, warrants further investigation and raises the question whether the true clinical picture as evidenced by T2LV and cerebral atrophy should be used for diagnostic purposes initially. One could argue that the presence of the highest levels of atrophy would be seen in those patients with the longest history of disease and would be expected to fall into either phenotype III or IV. However, the results of this study defy that logic as evidenced by the presence of 19% of the secondary progressive MS diagnosed patients falling under Type I and Type II and having only mild atrophy. Were these patients misdiagnosed with the current subtype or does the variability within the subtype represent an opportunity to expand the disease categories to include a place for those patients who do not follow traditional diagnostic principles? To answer these and other questions raised by the significant findings of this research, further studies utilizing an objective MS population-based median of the neuroimaging parameters presented here could be used as the reference point for calculating median splits as opposed to a stratification of a cross-sectional single institution study sample. Using the same methodological approach on a national average scale could potentially offer additional insight into the etiology of heterogeneity seen both among and within traditionally applied MS classifications.
http://dx.doi.org/10.1016/j.jns.2014.08.046 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: McGee J, Minagar A, Utilization of brain MRI with focus on cerebral lesions and atrophy to better characterize MS phenotypes, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.08.046
2
Editorial
Conflict of interest We wish to confirm that there are no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. References [1] Tauhid S, Neema M, Healy BC, Weiner HL, Bakshi R. MRI phenotypes based on cerebral lesions and atrophy in patients with multiple sclerosis. J Neurol Sci 2014. [2] Luo J, Yablonskiy DA, Hildebolt CF, Lancia S, Cross AH. Gradient echo magnetic resonance imaging correlates with clinical measures and allows visualization of veins within multiple sclerosis lesions. Mult Scler J 2014;20(3):349–55.
[3] Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, et al. Evidence of a two-stage disability progression in multiple sclerosis. Brain 2010;133:1900–13.
Jeanie McGee Alireza Minagar Department of Neurology, Louisiana State University Health Sciences Center — Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA E-mail address: [email protected] (A. Minagar). 27 August 2014 Available online xxxx
Please cite this article as: McGee J, Minagar A, Utilization of brain MRI with focus on cerebral lesions and atrophy to better characterize MS phenotypes, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.08.046
