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Visualisation of the medial longitudinal fasciculus using fibre tractography in multiple sclerosis patients with internuclear ophthalmoplegia

Irish Journal of Medical Science (1971 -) volume 185, pages 393–402 (2016)Cite this article

Abstract

Background

This study investigates the use of fibre tractography to facilitate visualisation of the medial longitudinal fasciculus (MLF) and the impact of internuclear ophthalmoplegia (INO) causing lesions on these reconstructions of the tract. Improved visualisation of such tracts may improve knowledge, understanding and confidence related to neurological conditions.

Aims

To explore the use of fibre tractography for the visualisation of the MLF in patients with INO.

Methods

Twelve MS subjects with clinical evidence of INO and 12 matched controls underwent magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), of the brain. Fibre tractography reconstructions were then evaluated and validated by an experienced neuroanatomist.

Results

The evaluating neuroanatomist confirmed that the MLF had been reproduced in all of the reconstructed cases (fibre tractography was unsuccessful in five cases). The sensitivity of fibre tractography to MLF pathology was 58.3 % while the specificity was much higher at 85.7 % with a positive predictive value of 87.5 % and a negative predictive value of 54.6 %, with excellent intra-reader reliability.

Conclusion

This study demonstrates that fibre tractography of the MLF can potentially be performed with a view to facilitating improved visualisation of the tract and associated pathology in cases of INO. This may help explain the association between lesion type and location with clinical symptomatology and may assist in monitoring disease progression. These reconstructions may provide a valuable addition to the teaching and understanding of clinical signs related to subtle pathology.

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References

  1. Matthews B (1998) Symptoms and signs of multiple sclerosis. In: Compston A, Ebers G, Lassmann H, McDonald I, Matthews B, Wekerle H (eds) McAlpine’s multiple sclerosis, 3rd edn. Churchill Livingstone, London, pp 157–162

    Google Scholar 

  2. Poser CM, Brinar VV (2001) Diagnostic criteria for multiple sclerosis. Clin Neurol Neurosurg 103(1):1–11

    Article  CAS  PubMed  Google Scholar 

  3. Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302

    Article  PubMed  PubMed Central  Google Scholar 

  4. Frohman EM, O’Suilleabhain P, Dewey RB Jr et al (2003) A new measure of dysconjugacy in INO: the first-pass amplitude. J Neurol Sci 210:65–71

    Article  PubMed  Google Scholar 

  5. Leigh RJ, Wolinsky JS (2001) Keeping an eye on MS. Neurology 57(5):751–752

    Article  CAS  PubMed  Google Scholar 

  6. Comi G, Filippi M, Barkhof F, Early Treatment of Multiple Sclerosis Study Group et al (2001) Effect of early interferon treatment on conversion to definite multiple sclerosis. Lancet 357(9268):1576–1582

    Article  CAS  PubMed  Google Scholar 

  7. Miller DH, Grossmann RI, Reingold SC et al (1998) The role of magnetic resonance techniques in understanding and managing multiple sclerosis. Brain 121(1):3–24

    Article  PubMed  Google Scholar 

  8. Pelidou S, Giannopoulos S, Tzavidi S et al (2008) Multiple sclerosis presented as clinically isolated syndrome: the need for early diagnosis and treatment. Ther Clin Risk Manag 4(3):627–630

    PubMed  PubMed Central  Google Scholar 

  9. Frohman EM, Zhang H, Kramer PD et al (2001) MRI characteristics of the MLF in MS patients with chronic internuclear ophthalmoparesis. Neurology 57(5):762–768

    Article  CAS  PubMed  Google Scholar 

  10. Miller D, Barkhof F, Montalban X et al (2005) Clinically isolated syndrome suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 4:281–288

    Article  PubMed  Google Scholar 

  11. Muri RM, Meienberg O (1985) The clinical spectrum of internuclear ophthalmoplegia in multiple sclerosis. Arch Neurol 42:851–855

    Article  CAS  PubMed  Google Scholar 

  12. Savino PJ (1996) Neuro-ophthalmology. In: Tasman W, Jaeger EA (eds) Atlas of clinical ophthalmology. Lippincott Raven, Philadelphia, pp 310–311

    Google Scholar 

  13. Lavin PJM, Donahue SP (20040. Disorders of supranuclear control of ocular motility. In: Yanoff M, Duker JS (eds) Ophthalmology. Part 11: Neuro-ophthalmology, 2nd edn. Mosby, St. Louis, pp 1310

  14. Lassmann H (1998) Pathology of multiple sclerosis. In: Compston A, Ebers G, Lassmann H, McDonald I, Matthews B, Wekerle H (eds) McAlpine’s multiple sclerosis, 3rd edn. Churchill Livingstone, London, pp 326–328

    Google Scholar 

  15. Schmierera K, Wheeler-Kingshotta CAM, Boulbya PA et al (2007) Diffusion tensor imaging of post mortem multiple sclerosis brain. Neuroimage 35(2):467–477

    Article  Google Scholar 

  16. Sakaie K, Takakasi M, Dimitrov I et al (2011) Diffusion tensor imaging the medial longitudinal fasciculus in INO: opportunities and challenges. Ann NY Acad Sci 1233:307–312

    Article  PubMed  Google Scholar 

  17. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452

    Article  CAS  PubMed  Google Scholar 

  18. Nucifora PG, Verma R, Lee SK et al (2007) Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. Radiology 245(2):367–384

    Article  PubMed  Google Scholar 

  19. Atlas SW, Grossman RI, Savino PJ et al (1987) Internuclear ophthalmoplegia: MR-anatomic correlation. Am J Neuroradiol 8(2):243–247

    CAS  PubMed  Google Scholar 

  20. Barnes D, McDonald WI (1992) The ocular manifestations of multiple sclerosis. 2. Abnormalities of eye movements. J Neurol Neurosurg Psychiatry 55(10):863–868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Marx JJ, Thoemke F, Fitzek S et al (2001) A new method to investigate brain stem structural-functional correlations using digital post-processing MRI—reliability in ischemic internuclear ophthalmoplegia. Eur J Neurol 8:489–493

    Article  CAS  PubMed  Google Scholar 

  22. Bronstein AM, Rudge P, Gresty MA et al (1990) Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. II Gaze palsy and internuclear ophthalmoplegia. J Neurol Neurosurg Psychiatry 53:200–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Frohman EM, Frohman TC, O’Suilleabhain P et al (2002) Quantitative oculographic characterisation of internuclear ophthalmoparesis in multiple sclerosis: the versional dysconjugacy index Z score. J Neurol Neurosurg Psychiatry 73:51–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Frohman TC, Frohman EM, O’Suilleabhain P et al (2003) Accuracy of clinical detection of INO in MS: corroboration with quantitative infrared oculography. Neurology 61:848–850

    Article  CAS  PubMed  Google Scholar 

  25. Balanos I, Lozano D, Cantú C (2004) Internuclear ophthalmoplegia: causes and long-term follow-up in 65 patients. Acta Neurol Scand 110:161–165

    Article  Google Scholar 

  26. McNulty JP, Lonergan R, Brennan PC et al (2014) Diagnostic efficacy of conventional MRI pulse sequences in the detection of lesions causing internuclear ophthalmoplegia in multiple sclerosis patients. Clin Neuroradiol. doi:10.1007/s00062-014-0295-5

    PubMed  Google Scholar 

  27. Okada T, Miki Y, Fushimi Y et al (2006) Diffusion-tensor fiber tractography: intraindividual comparison of 3.0-T and 1.5-T MR imaging. Radiology 238(2):668–678

    Article  PubMed  Google Scholar 

  28. Pagani E, Filippi M, Rocca MA et al (2005) A method for obtaining tract-specific diffusion tensor MRI measurements in the presence of disease: application to patients with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 26:258–265

    Article  CAS  PubMed  Google Scholar 

  29. Hesseltine SM, Law M, Babb J et al (2006) Diffusion tensor imaging in multiple sclerosis: assessment of regional differences in the axial plane within normal-appearing cervical spinal cord. Am J Neuroradiol 27:1189–1193

    CAS  PubMed  Google Scholar 

  30. Dziedzic T, Metz I, Dallenga T et al (2010) Wallerian degeneration: a major component of early axonal pathology in multiple sclerosis. Brain Pathol 20(5):976–985

    PubMed  Google Scholar 

  31. Sundgren PC, Dong Q, Gómez-Hassan D et al (2004) Diffusion tensor imaging of the brain: review of clinical applications. Neuroradiology 46(5):339–350

    Article  CAS  PubMed  Google Scholar 

  32. Alexander AL, Hasan K, Lazar M et al (2007) Analysis of partial volume effects in diffusion-tensor MRI. Magn Reson Med 45:770–780

    Article  Google Scholar 

  33. Hunsche S, Moseley ME, Stoeter P et al (2001) Diffusion-tensor MR imaging at 1.5 and 3.0 T: initial observations. Radiology 221(2):550–556

    Article  CAS  PubMed  Google Scholar 

  34. Mamata H, Mamata Y, Westin CF et al (2002) High-resolution line scan diffusion tensor MR imaging of white matter fiber tract anatomy. Am J Neuroradiol 23(1):67–75

    PubMed  PubMed Central  Google Scholar 

  35. Guo AC, Jewells VL, Provenzale JM (2001) Analysis of normal-appearing white matter in multiple sclerosis: comparison of diffusion tensor MR imaging and magnetization transfer imaging. Am J Neuroradiol 22(10):1893–1900

    CAS  PubMed  Google Scholar 

  36. Guo AC, MacFall JR, Provenzale JM (2002) Multiple sclerosis: diffusion tensor MR imaging for evaluation of normal-appearing white matter. Radiology 222(3):729–736

    Article  PubMed  Google Scholar 

  37. Ohgiya Y, Oka M, Hiwatashi A et al (2007) Diffusion tensor MR imaging of the cervical spinal cord in patients with multiple sclerosis. Eur Radiol 17:2499–2504

    Article  PubMed  Google Scholar 

  38. Yu C, Lin F, Li K et al (2008) Pathogenesis of normal-appearing white matter damage in neuromyelitis optica: diffusion-tensor MR imaging. Radiology 246(1):222–228

    Article  PubMed  Google Scholar 

  39. Jozefowicz RF (1994) Neurophobia: the fear of neurology among medical students. Arch Neurol 51(4):328–329

    Article  CAS  PubMed  Google Scholar 

  40. Arnts H, Kleinnijenhuis M, Kooloos JG et al (2014) Combining fiber dissection, plastination, and tractography for neuroanatomical education: revealing the cerebellar nuclei and their white matter connections. Am Ass Anat 7(1):47–55

    Google Scholar 

  41. Hazelton L (2011) Changing concepts of neuroanatomy teaching in medical education. Teach Learn Med Int J 23(4):359–364

    Article  Google Scholar 

  42. Haines DE, Hutchins JB, Lynch JC (2002) Medical neurobiology: do we teach neurobiology in a format that is relevant to the clinical setting? Anat Rec 269(2):99–106

    Article  PubMed  Google Scholar 

  43. Naaz F, Chariker JH, Pani JR (2014) Computer-based learning: graphical integration of whole and sectional neuroanatomy improves long-term retention. Cogn Instr 32(1):44–64

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was supported by the UCD Seed Funding and Overhead Investment Plan Schemes, the UCD School of Medicine and Medical Science Research Support Scheme and a National Multiple Sclerosis Society (USA) Research Award.

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Authors and Affiliations

  1. School of Medicine, University College Dublin, Health Sciences Centre, Belfield, Dublin 4, Ireland

    J. P. McNulty, J. Bannigan, R. O’Laoide, L. A. Rainford & N. Tubridy

  2. Department of Neurology, St. Vincent’s University Hospital, Dublin 4, Ireland

    R. Lonergan & N. Tubridy

  3. Department of Radiology, St. Vincent’s University Hospital, Dublin 4, Ireland

    R. O’Laoide

Authors
  1. J. P. McNulty
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  2. R. Lonergan
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  3. J. Bannigan
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  4. R. O’Laoide
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  5. L. A. Rainford
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  6. N. Tubridy
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Corresponding author

Correspondence to J. P. McNulty.

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Funding

This study was supported by the UCD Seed Funding and Overhead Investment Plan Schemes, the UCD School of Medicine and Medical Science Research Support Scheme and a National Multiple Sclerosis Society (USA) Research Award.

Conflict of interest

Author A received research funding through the UCD Seed Funding and Overhead Investment Plan Schemes, the UCD School of Medicine and Medical Science Research Support Scheme and a National Multiple Sclerosis Society (USA) Research Award. Author B received an educational grant from pharmaceutical industry to fund participation in American Academy of Neurology meeting. Authors C, D and E have no conflicts of interest. Author F received research funding through the UCD Seed Funding and Overhead Investment Plan Schemes, the UCD School of Medicine and Medical Science Research Support Scheme and a National Multiple Sclerosis Society (USA) Research Award.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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McNulty, J.P., Lonergan, R., Bannigan, J. et al. Visualisation of the medial longitudinal fasciculus using fibre tractography in multiple sclerosis patients with internuclear ophthalmoplegia. Ir J Med Sci 185, 393–402 (2016). https://doi.org/10.1007/s11845-016-1405-y

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  • DOI: https://doi.org/10.1007/s11845-016-1405-y

Keywords

  • Fibre tractography
  • Internuclear ophthalmoplegia
  • Magnetic resonance imaging
  • Medial longitudinal fasciculus
  • Multiple sclerosis