Advertisement

Journal of Neurology

, Volume 265, Issue 4, pp 783–792 | Cite as

Insular multiple sclerosis lesions are associated with erectile dysfunction

  • Klemens Winder
  • Ralf A. Linker
  • Frank Seifert
  • Martina Deutsch
  • Tobias Engelhorn
  • Arnd Dörfler
  • De-Hyung Lee
  • Katharina M. Hösl
  • Max J. Hilz
Original Communication

Abstract

Erectile function (EF) is frequently compromised in men with multiple sclerosis (MS). Functional neuroimaging in healthy men identified a network of brain areas, such as the insula, visual and somatosensory association areas, cingulate gyrus, prefrontal cortex, as well as subcortical regions, contributing to EF. This study intended to determine associations between EF deterioration during MS and cerebral MS-associated lesion sites. In 31 men with MS (mean age 38.2 ± 11.2 years), we evaluated MS-related EF deterioration by comparing scores of the 5-item International Index of Erectile Function-5 questionnaire (IIEF5) at the time of study and retrospectively, 3 months prior to MS diagnosis, by calculating score differences as DeltaIIEF5 (DeltaIIEF5 score < 0 indicated EF deterioration). To assess the impact of confounding factors of EF, patient age, disease duration, disease severity, depressiveness, bladder and bowel symptoms, and total cerebral MS lesion volume were correlated with DeltaIIEF5 scores (Spearman rank correlation) and compared between patients with and without EF deterioration (t tests or Mann–Whitney U test). MS lesions were assessed on T2-weighted magnetic resonance imaging (MRI; 1.5 or 3 T). We determined the lesion overlap (prevalence of identical lesion sites among patients), subtracted lesion overlaps in patients without EF deterioration from overlaps in patients with EF deterioration, and compared DeltaIIEF5 scores voxel-wise between patients with and without lesions in a given voxel (t test; significance: p < 0.05). In 14 patients (45.2%), DeltaIIEF5 scores indicated EF deterioration. DeltaIIEF5 scores were not associated with age (ρ = 0.06; p = 0.74), disease duration (ρ = 0.26; p = 0.15), disease severity (ρ = − 0.19; p = 0.31), depressiveness (ρ = 0.07; p = 0.72), bladder symptoms (ρ = − 0.11; p = 0.57), bowel symptoms (ρ = 0.17; p = 0.37), and total lesion volume (ρ = − 0.13; p = 0.47). The voxel-wise analysis showed associations between EF deterioration and MS lesions primarily in the bilateral, and predominantly left juxtacortical insular region. In conclusion, MS lesions particularly in the left insular region, which is activated with sexual arousal, contribute to erectile dysfunction.

Keywords

Multiple sclerosis Sexual dysfunction Erectile dysfunction Autonomic dysfunction Voxel-based lesion symptom mapping 

Notes

Compliance with ethical standards

Conflicts of interest

MJH reports grants and personal fees from Bayer HealthCare pharmaceuticals, during the conduct of the study; grants and personal fees from Genzyme, a Sanofi company, grants and personal fees from Novartis Pharma GmbH, outside the submitted work. DHL reports grants and personal fees from Bayer HealthCare Pharmaceuticals, grants and personal fees from Biogen Idec, grants and personal fees from Merck Serono, grants and personal fees from Novartis Pharma GmbH, grants and personal fees from TEVA Pharmaceutical Industries LTD, outside the submitted work. RAL reports grants and personal fees from Bayer HealthCare Pharmaceuticals, grants and personal fees from Biogen Idec, grants and personal fees from Merck Serono, grants and personal fees from Novartis Pharma GmbH, grants and personal fees from Roche, grants and personal fees from TEVA Pharmaceutical Industries LTD, and from Novartis foundation, outside the submitted work. RAL holds an endowed professorship supported by the Novartis Foundation.

Ethical approval

The study has been approved by the local ethics committee and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent has been obtained for all study participants.

References

  1. 1.
    Zivadinov R, Zorzon M, Locatelli L, Stival B, Monti F, Nasuelli D, Tommasi MA, Bratina A, Cazzato G (2003) Sexual dysfunction in multiple sclerosis: a MRI, neurophysiological and urodynamic study. J Neurol Sci 210:73–76CrossRefPubMedGoogle Scholar
  2. 2.
    Zorzon M, Zivadinov R, Locatelli L, Stival B, Nasuelli D, Bratina A, Bosco A, Tommasi MA, Pozzi Mucelli RS, Ukmar M, Cazzato G (2003) Correlation of sexual dysfunction and brain magnetic resonance imaging in multiple sclerosis. Mult Scler 9:108–110CrossRefPubMedGoogle Scholar
  3. 3.
    Rees PM, Fowler CJ, Maas CP (2007) Sexual function in men and women with neurological disorders. Lancet 369:512–525CrossRefPubMedGoogle Scholar
  4. 4.
    Betts CD, Jones SJ, Fowler CG, Fowler CJ (1994) Erectile dysfunction in multiple sclerosis. Associated neurological and neurophysiological deficits, and treatment of the condition. Brain 117(Pt 6):1303–1310CrossRefPubMedGoogle Scholar
  5. 5.
    Vigeveno RM, Wiebenga OT, Wattjes MP, Geurts JJ, Barkhof F (2012) Shifting imaging targets in multiple sclerosis: from inflammation to neurodegeneration. J Magn Reson Imaging 36:1–19CrossRefPubMedGoogle Scholar
  6. 6.
    Ge Y (2006) Multiple sclerosis: the role of MR imaging. AJNR Am J Neuroradiol 27:1165–1176PubMedGoogle Scholar
  7. 7.
    Arnow BA, Desmond JE, Banner LL, Glover GH, Solomon A, Polan ML, Lue TF, Atlas SW (2002) Brain activation and sexual arousal in healthy, heterosexual males. Brain 125:1014–1023CrossRefPubMedGoogle Scholar
  8. 8.
    Ferretti A, Caulo M, Del Gratta C, Di Matteo R, Merla A, Montorsi F, Pizzella V, Pompa P, Rigatti P, Rossini PM, Salonia A, Tartaro A, Romani GL (2005) Dynamics of male sexual arousal: distinct components of brain activation revealed by fMRI. Neuroimage 26:1086–1096CrossRefPubMedGoogle Scholar
  9. 9.
    Miyagawa Y, Tsujimura A, Fujita K, Matsuoka Y, Takahashi T, Takao T, Takada S, Matsumiya K, Osaki Y, Takasawa M, Oku N, Hatazawa J, Kaneko S, Okuyama A (2007) Differential brain processing of audiovisual sexual stimuli in men: comparative positron emission tomography study of the initiation and maintenance of penile erection during sexual arousal. Neuroimage 36:830–842CrossRefPubMedGoogle Scholar
  10. 10.
    Moulier V, Mouras H, Pélégrini-Issac M, Glutron D, Rouxel R, Grandjean B, Bittoun J, Stoléru S (2006) Neuroanatomical correlates of penile erection evoked by photographic stimuli in human males. Neuroimage 33:689–699CrossRefPubMedGoogle Scholar
  11. 11.
    Winder K, Linker RA, Seifert F, Deutsch M, Engelhorn T, Dörfler A, Lee DH, Hösl KM, Hilz MJ (2016) Neuroanatomic correlates of female sexual dysfunction in multiple sclerosis. Ann Neurol 80:490–498CrossRefPubMedGoogle Scholar
  12. 12.
    Winder K, Seifert F, Köhrmann M, Crodel C, Kloska S, Dörfler A, Hösl KM, Schwab S, Hilz MJ (2017) Lesion mapping of stroke-related erectile dysfunction. Brain 140:1706–1717CrossRefPubMedGoogle Scholar
  13. 13.
    Winder K, Seifert F, Ohnemus T, Sauer EM, Kloska S, Dörfler A, Hilz MJ, Schwab S, Köhrmann M (2015) Neuroanatomic correlates of poststroke hyperglycemia. Ann Neurol 77:262–268CrossRefPubMedGoogle Scholar
  14. 14.
    Rorden C, Karnath HO, Bonilha L (2007) Improving lesion-symptom mapping. J Cogn Neurosci 19:1081–1088CrossRefPubMedGoogle Scholar
  15. 15.
    Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O’Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452CrossRefPubMedGoogle Scholar
  17. 17.
    Richter P, Werner J, Heerlein A, Kraus A, Sauer H (1998) On the validity of the Beck Depression Inventory. A review. Psychopathology 31:160–168CrossRefPubMedGoogle Scholar
  18. 18.
    Sanders AS, Foley FW, LaRocca NG, Zemon V (2000) The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19). Sex Disabil 18:3–26CrossRefGoogle Scholar
  19. 19.
    Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM (1999) Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 11:319–326CrossRefPubMedGoogle Scholar
  20. 20.
    Rorden C, Bonilha L, Fridriksson J, Bender B, Karnath HO (2012) Age-specific CT and MRI templates for spatial normalization. Neuroimage 61:957–965CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26:839–851CrossRefPubMedGoogle Scholar
  22. 22.
    Hilz MJ (2008) Female and male sexual dysfunction. In: Low PA, Benarroch EE (eds) Clinical autonomic disorders, 3rd edn. Lippincott Williams and Wilkins, Philadelphia, pp 657–711Google Scholar
  23. 23.
    Seifert CL, Schönbach EM, Magon S, Gross E, Zimmer C, Förschler A, Tölle TR, Mühlau M, Sprenger T, Poppert H (2016) Headache in acute ischaemic stroke: a lesion mapping study. Brain 139:217–226CrossRefPubMedGoogle Scholar
  24. 24.
    Schwartz MF, Faseyitan O, Kim J, Coslett HB (2012) The dorsal stream contribution to phonological retrieval in object naming. Brain 135:3799–3814CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289CrossRefPubMedGoogle Scholar
  26. 26.
    Barak Y, Achiron A, Elizur A, Gabbay U, Noy S, Sarova-Pinhas I (1996) Sexual dysfunction in relapsing-remitting multiple sclerosis: magnetic resonance imaging, clinical, and psychological correlates. J Psychiatry Neurosci 21:255–258PubMedPubMedCentralGoogle Scholar
  27. 27.
    Winder K, Seifert F, Koehn J, Deutsch M, Engelhorn T, Dörfler A, Lee DH, Linker RA, Hilz MJ (2015) Site and size of multiple sclerosis lesions predict enhanced or decreased female orgasmic function. J Neurol 262:2731–2738CrossRefPubMedGoogle Scholar
  28. 28.
    Saper CB (2002) The central autonomic nervous system: conscious visceral perception and autonomic pattern generation. Annu Rev Neurosci 25:433–469CrossRefPubMedGoogle Scholar
  29. 29.
    King AB, Menon RS, Hachinski V, Cechetto DF (1999) Human forebrain activation by visceral stimuli. J Comp Neurol 413:572–582CrossRefPubMedGoogle Scholar
  30. 30.
    Cechetto DF, Shoemaker JK (2009) Functional neuroanatomy of autonomic regulation. Neuroimage 47:795–803CrossRefPubMedGoogle Scholar
  31. 31.
    Zhang ZH, Rashba S, Oppenheimer SM (1998) Insular cortex lesions alter baroreceptor sensitivity in the urethane-anesthetized rat. Brain Res 813:73–81CrossRefPubMedGoogle Scholar
  32. 32.
    Oppenheimer SM, Kedem G, Martin WM (1996) Left-insular cortex lesions perturb cardiac autonomic tone in humans. Clin Auton Res 6:131–140CrossRefPubMedGoogle Scholar
  33. 33.
    Yoon BW, Morillo CA, Cechetto DF, Hachinski V (1997) Cerebral hemispheric lateralization in cardiac autonomic control. Arch Neurol 54:741–744CrossRefPubMedGoogle Scholar
  34. 34.
    Hilz MJ, Dütsch M, Perrine K, Nelson PK, Rauhut U, Devinsky O (2001) Hemispheric influence on autonomic modulation and baroreflex sensitivity. Ann Neurol 49:575–584CrossRefPubMedGoogle Scholar
  35. 35.
    Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC (1992) Cardiovascular effects of human insular cortex stimulation. Neurology 42:1727–1732CrossRefPubMedGoogle Scholar
  36. 36.
    Critchley HD, Corfield DR, Chandler MP, Mathias CJ, Dolan RJ (2000) Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans. J Physiol 523(Pt 1):259–270CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Benarroch EE (1997) The central autonomic network. In: Low PA (ed) Clinical autonomic disorders. Lippincott-Raven Publishers, Philadelphia, pp 17–23Google Scholar
  38. 38.
    van Walderveen MA, Kamphorst W, Scheltens P, van Waesberghe JH, Ravid R, Valk J, Polman CH, Barkhof F (1998) Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 50:1282–1288CrossRefPubMedGoogle Scholar
  39. 39.
    De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS, Antel JP, Arnold DL (1998) Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121(Pt 8):1469–1477CrossRefPubMedGoogle Scholar
  40. 40.
    Hilz MJ (2016) Cardiac stunning as first manifestation of multiple sclerosis: a case report reminding us not to overlook cardiovascular autonomic dysfunction in multiple sclerosis. Mult Scler 22:847–848CrossRefPubMedGoogle Scholar
  41. 41.
    Kaplan TB, Berkowitz AL, Samuels MA (2015) Cardiovascular dysfunction in multiple sclerosis. Neurologist 20:108–114CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology, University Hospital ErlangenFriedrich-Alexander-University Erlangen-Nürnberg (FAU)ErlangenGermany
  2. 2.Department of Neuroradiology, University Hospital ErlangenFriedrich-Alexander-University Erlangen-NürnbergErlangenGermany
  3. 3.Department of Psychiatry and PsychotherapyParacelsus Medical UniversityNurembergGermany

Personalised recommendations