1. In The Name of God

2. Multiple Sclerosis and Normal MRI new modalities for problems solving

3. Multiple Sclerosis (MS) Is not a proclamation and religious diagnosis. Is not a proclamation and religious diagnosis. Is not purely a “ evidence- based medicine ” dependent diagnosis. Is not purely a “ evidence- based medicine ” dependent diagnosis. But it is a improvisational and really have a dynamic process for diagnosis. But it is a improvisational and really have a dynamic process for diagnosis.

4. Why ? We want to insert MS at our differential diagnosis in most of times. We want to insert MS at our differential diagnosis in most of times.

5. Because: MS is a heterogeneous disease and like to TB and Zigma is a great imitator. MS is a heterogeneous disease and like to TB and Zigma is a great imitator. We can not practice with principle of parsimony or Occam ’ s Razor at all of times. We can not practice with principle of parsimony or Occam ’ s Razor at all of times. MS have high prevalence, specially young peoples and reported in two limits of age. MS have high prevalence, specially young peoples and reported in two limits of age.

6. Why ? Occasionally we fear to insert MS at our differential diagnosis list. Occasionally we fear to insert MS at our differential diagnosis list.

7. Because: Many important alternative diagnosis (specially vascular and leukodystrophy in two age limits) Many important alternative diagnosis (specially vascular and leukodystrophy in two age limits) High prevalence of MS and frightening from overdiagnosis. High prevalence of MS and frightening from overdiagnosis. Many differentials of MS have similar clinical and paraclinical manifestations. Many differentials of MS have similar clinical and paraclinical manifestations. Unusual manifestation (MS variants). Unusual manifestation (MS variants). Finally, a normal MRI. Finally, a normal MRI.

8. MRI (importance) Magnetic resonance imaging may even assist in earlier diagnosis of multiple sclerosis by enabling visualization of lesions in the brain that are clinically silent. Magnetic resonance imaging may even assist in earlier diagnosis of multiple sclerosis by enabling visualization of lesions in the brain that are clinically silent.

9. LIMITED ROLE OF MRI IN MS MRI is sensitive but less specific for the diagnosis of MS. MRI is sensitive but less specific for the diagnosis of MS. People with presenting in the early stages of multiple sclerosis have less or no lesion. People with presenting in the early stages of multiple sclerosis have less or no lesion. Accuracy of magnetic resonance imaging varies according to presenting symptoms (spinal). Accuracy of magnetic resonance imaging varies according to presenting symptoms (spinal). These suggested that the role of magnetic resonance imaging either in ruling in or ruling out a diagnosis of multiple sclerosis is limited. These suggested that the role of magnetic resonance imaging either in ruling in or ruling out a diagnosis of multiple sclerosis is limited.

10. MS remains a predominantly clinical diagnosis Why, MRI should be included in the work-up of patients with multiple sclerosis? Because of: certainty of the diagnosis, ruling out differential diagnoses, providing a baseline for monitoring disease progression, patient request, and patient reassurance, insurance companies request. Because of: certainty of the diagnosis, ruling out differential diagnoses, providing a baseline for monitoring disease progression, patient request, and patient reassurance, insurance companies request.

11. MRI (overdiagnosis) Use of magnetic resonance imaging to confirm multiple sclerosis on the basis of a single attack may lead to over-diagnosis and over-treatment. Use of magnetic resonance imaging to confirm multiple sclerosis on the basis of a single attack may lead to over-diagnosis and over-treatment.

12. MRI (underdiagnosis with normal results) Neurologists should discuss with their patients about diagnosis, treatment, and ultimate effect of potential errors of false negative magnetic resonance imaging results. Neurologists should discuss with their patients about diagnosis, treatment, and ultimate effect of potential errors of false negative magnetic resonance imaging results.

13. What is the best approach to this problem

14. In the Presence of a Normal MRI ?! Usually in the absence of other problems normal MRI is not a major problem in clinical practice. Usually in the absence of other problems normal MRI is not a major problem in clinical practice.

15. Many important alternative diagnosis (specially vascular and leukodystrophy in two age limits) Many important alternative diagnosis (specially vascular and leukodystrophy in two age limits) High prevalence of MS and frightening from overdiagnosis. High prevalence of MS and frightening from overdiagnosis. Many differentials of MS have similar clinical and paraclinical manifestations. Many differentials of MS have similar clinical and paraclinical manifestations. Unusual manifestation (MS variants). Unusual manifestation (MS variants). Finally, a normal MRI. Finally, a normal MRI.

16. Because: Low percent of normal MRI(3%). Low percent of normal MRI(3%). Many clinical and paraclinical tests are suggestive. Many clinical and paraclinical tests are suggestive. New technology in brain imaging dissolve this problem today's. New technology in brain imaging dissolve this problem today's.

17. New MR modalities Hypointense lesions load of T1- weighted images and MR Volumetry, High Tesla MRI, MRI with GAD, Magnetization Transfer Imaging (MTI), Diffusion Tensor Imaging (DTI), and Proton Magnetic Resonance Spectroscopy (H-MRS). Hypointense lesions load of T1- weighted images and MR Volumetry, High Tesla MRI, MRI with GAD, Magnetization Transfer Imaging (MTI), Diffusion Tensor Imaging (DTI), and Proton Magnetic Resonance Spectroscopy (H-MRS).

18. Use of other MR modalities ? Inability of conventional MRI to accurately depict the pathology of MS as regards to histopathologic heterogeneity of MS lesions and the pathological processes occurring in the Normal Appearing White Matter (NAWM). Inability of conventional MRI to accurately depict the pathology of MS as regards to histopathologic heterogeneity of MS lesions and the pathological processes occurring in the Normal Appearing White Matter (NAWM). The limitation of T2-weighted MRI (artifacts), in delineating tissue damage occurring in CNS. The limitation of T2-weighted MRI (artifacts), in delineating tissue damage occurring in CNS.

19. Magnetic Resonance Spectroscopy MR Spectroscopy is being increasingly used to identify many of brain lesions and to localize areas of their pathologic involvement. MR Spectroscopy is being increasingly used to identify many of brain lesions and to localize areas of their pathologic involvement.

20. Magnetic Resonance Spectroscopy The nuclei of a number of atoms (H, F, Li, Na, and p) are excited by the magnetic field. The nuclei of a number of atoms (H, F, Li, Na, and p) are excited by the magnetic field. As the energy of these nuclei returns to a baseline state, a "frequency signature" particular to each nucleus can be measured. As the energy of these nuclei returns to a baseline state, a "frequency signature" particular to each nucleus can be measured. Simply put, the magnitude of each peak in this "frequency signature" corresponds to Simply put, the magnitude of each peak in this "frequency signature" corresponds to the concentration of a particular atom in the brain region being assessed. the concentration of a particular atom in the brain region being assessed.

21. MR Spectroscopy Recent pathology studies have stressed the Recent pathology studies have stressed the importance of axonal pathology in MS, in lesions and in Normal Appearing White Matter (NAWM). importance of axonal pathology in MS, in lesions and in Normal Appearing White Matter (NAWM). Decrease in N-Acetyl Aspartate (NAA) has been used as an marker of axonal damage or loss that presumably appears secondary to inflammation or demyelination. Decrease in N-Acetyl Aspartate (NAA) has been used as an marker of axonal damage or loss that presumably appears secondary to inflammation or demyelination.

22. MR Spectroscopy Loss of neurons would thus predict a persistent reduction in the levels of NAA. Loss of neurons would thus predict a persistent reduction in the levels of NAA. There are now many studies in the literature that report a reduction of NAA in acute lesions, in chronic multiple sclerosis lesions, in areas of normal appearing white matter, and in gray matter. There are now many studies in the literature that report a reduction of NAA in acute lesions, in chronic multiple sclerosis lesions, in areas of normal appearing white matter, and in gray matter.

23. Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy Juan Luis Ruiz- Pe ñ a et al

24. Background: What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis.

25. Background: Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability.

26. Methods: Thirty one patients (9 male and 22 female) with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0 – 5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Thirty one patients (9 male and 22 female) with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0 – 5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day.

27. Results: A statistically significant correlation was found (p < 0.05) between disability (measured by Expanded Disability Scale Score) and N-Acetyl Aspartate (NAA/Cr ratio) levels in normal appearing white matter in these patients. A statistically significant correlation was found (p < 0.05) between disability (measured by Expanded Disability Scale Score) and N-Acetyl Aspartate (NAA/Cr ratio) levels in normal appearing white matter in these patients.

28. Conclusions: There is correlation between disability (measured by Expanded Disability Scale Score) and the NAA/Cr ratio in normal appearing white matter. There is correlation between disability (measured by Expanded Disability Scale Score) and the NAA/Cr ratio in normal appearing white matter.