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Sonographic basal ganglia alterations are related to non-motor symptoms in multiple sclerosis

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Abstract

The anatomical basis of cognitive dysfunction and other non-motor symptoms in multiple sclerosis (MS) is poorly understood. In MS patients, transcranial sonography (TCS) shows neurodegenerative disease-like lesions of the substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation. The present study deals with the question of whether sonographic changes of SN, brainstem raphe, lenticular nucleus (LN) or caudate nucleus are related to non-motor symptoms of MS. We used TCS to investigate 54 MS patients and 54 age- and sex-matched healthy subjects. Degree of cognitive (executive) dysfunction, fatigue, depression, and urinary urge incontinence in MS patients was assessed using the Paced Auditory Serial Addition Test, the Faces Symbol Test, the Modified Fatigue Impact Scale, the Beck Depression Inventory, and the Urinary Distress Inventory. Abnormal TCS findings of SN, brainstem raphe, LN, and caudate nucleus were found in 13, 7, 11, and 6% of the healthy subjects, but in 54, 43, 62, and 41% (each, p < 0.001) of the MS patients, with similar frequency in relapsing-remitting and primary or secondary progressive MS patients. Sonographic alteration of the LN correlated with cognitive dysfunction. Combined alteration of both, LN and SN, was clearly associated with cognitive dysfunction and cognitive fatigue. The combined sonographic alteration of SN and brainstem raphe indicated severe urinary urge incontinence irrespective of the presence of spinal MS lesions. No relation was found between depression and any of the TCS findings. These findings suggest that neurodegenerative processes affecting deep brain structures contribute to cognitive and autonomic dysfunction in MS.

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References

  1. Hauser SL, Oksenberg JR (2006) The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52:61–76

    Article  CAS  PubMed  Google Scholar 

  2. Nortvedt MW, Riise T, Myhr KM, Landtblom AM, Bakke A, Nylane HI (2001) Reduced quality of life among multiple sclerosis patients with sexual disturbance and bladder dysfunction. Mult Scler 7:231–235

    CAS  PubMed  Google Scholar 

  3. Crayton H, Heyman RA, Rossman HS (2004) A multimodal approach to managing the symptoms of multiple sclerosis. Neurology 63(Suppl 5):S12–S18

    PubMed  Google Scholar 

  4. Amato MP, Zipoli V, Portaccio E (2006) Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies. J Neurol Sci 245:41–46

    Article  PubMed  Google Scholar 

  5. Hadjimichael O, Vollmer T, Oleen-Burkey M, North American Research Committee on Multiple Sclerosis (2008) Fatigue characteristics in multiple sclerosis: the North American Research Committee on Multiple Sclerosis (NARCOMS) survey. Health Qual Life Outcomes 6:100

    Article  PubMed  Google Scholar 

  6. Marrie RA, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T (2009) The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed, and undertreated. Mult Scler 15:385–392

    Article  CAS  PubMed  Google Scholar 

  7. Hadjimichael O (2002) NARCOMS report. Bladder symptoms among registry participants. Mult Scler Q Rep 21:16–19

    Google Scholar 

  8. Hohol MJ, Guttmann CR, Orav J, Mackin GA, Kikinis R, Khoury SJ, Jolesz FA, Weiner HL (1997) Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis. Arch Neurol 54:1018–1025

    CAS  PubMed  Google Scholar 

  9. Zivadinov R, Sepcic J, Nasuelli D, De Masi R, Bragadin LM, Tommasi MA, Zambito-Marsala S, Moretti R, Bratina A, Ukmar M, Pozzi-Mucelli RS, Grop A, Cazzato G, Zorzon M (2001) A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 70:773–780

    Article  CAS  PubMed  Google Scholar 

  10. Benedict RHB, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61:226–230

    Article  PubMed  Google Scholar 

  11. Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R (2006) Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 66:685–692

    Article  PubMed  Google Scholar 

  12. Berg D, Supprian T, Thomae J, Warmuth-Metz M, Horowski A, Zeiler B, Magnus T, Rieckmann P, Becker G (2000) Lesion pattern in patients with multiple sclerosis and depression. Mult Scler 6:156–162

    CAS  PubMed  Google Scholar 

  13. Bakshi R, Czarnecki D, Shaikh ZA, Priore RL, Janardhan V, Kaliszky Z, Kinkel PR (2000) Brain MRI lesions and atrophy are related to depression in multiple sclerosis. Neuroreport 11:1153–1158

    Article  CAS  PubMed  Google Scholar 

  14. Feinstein A, Roy P, Lobaugh NJ, Feinstein K, O’Connor P, Black SE (2004) Structural brain abnormalities in multiple sclerosis patients with major depression. Neurology 62:586–590

    CAS  PubMed  Google Scholar 

  15. Feinstein A, O’Connor P, Akbar N, Moradzadeh L, Scott CJ, Lobaugh NJ (2010) Diffusion tensor imaging abnormalities in depressed multiple sclerosis patients. Mult Scler 16:189–196

    Article  CAS  PubMed  Google Scholar 

  16. Walter U, Kanowski M, Kaufmann J, Grossmann A, Benecke R, Niehaus L (2008) Contemporary ultrasound systems allow high-resolution transcranial imaging of small echogenic deep intracranial structures similarly as MRI: a phantom study. Neuroimage 40:551–558

    Article  PubMed  Google Scholar 

  17. Walter U, Skoloudík D, Berg D (2010) Transcranial sonography findings related to non-motor features of Parkinson’s disease. J Neurol Sci 289(1–2):123–127

    Article  PubMed  Google Scholar 

  18. Becker T, Becker G, Seufert J, Hofmann E, Lange KW, Naumann M, Lindner A, Reichmann H, Riederer P, Beckmann H, Reiners K (1997) Parkinson’s disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography. J Neurol Neurosurg Psychiatry 63:590–596

    Article  CAS  PubMed  Google Scholar 

  19. Berg D, Supprian T, Hofmann E, Zeiler B, Jäger A, Lange KW, Reiners K, Becker T, Becker G (1999) Depression in Parkinson’s disease: brainstem midline alteration on transcranial sonography and magnetic resonance imaging. J Neurol 246:1186–1193

    Article  CAS  PubMed  Google Scholar 

  20. Walter U, Dressler D, Wolters A, Wittstock M, Benecke R (2006) Overactive bladder in Parkinson’s disease: alteration of brainstem raphe detected by transcranial sonography. Eur J Neurol 13:1291–1297

    Article  CAS  PubMed  Google Scholar 

  21. Walter U, Hoeppner J, Prudente-Morrissey L, Horowski S, Herpertz SC, Benecke R (2007) Parkinson’s disease-like midbrain sonography abnormalities are frequent in depressive disorders. Brain 130:1799–1807

    Article  PubMed  Google Scholar 

  22. Walter U, Dressler D, Wolters A, Wittstock M, Benecke R (2007) Transcranial brain sonography findings in clinical subgroups of idiopathic Parkinson’s disease. Mov Disord 22:48–54

    Article  PubMed  Google Scholar 

  23. Walter U, Wagner S, Horowski S, Benecke R, Zettl UK (2009) Transcranial brain sonography findings predict disease progression in multiple sclerosis. Neurology 73:1010–1017

    Article  CAS  PubMed  Google Scholar 

  24. Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911

    CAS  PubMed  Google Scholar 

  25. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846

    Article  PubMed  Google Scholar 

  26. Rieckmann P, Toyka KV, Bassetti C, Beer K, Beer S, Buettner U, Chofflon M, Götschi-Fuchs M, Hess K, Kappos L, Kesselring J, Goebels N, Ludin HP, Mattle H, Schluep M, Vaney C, Baumhackl U, Berger T, Deisenhammer F, Fazekas F, Freimüller M, Kollegger H, Kristoferitsch W, Lassmann H, Markut H, Strasser-Fuchs S, Vass K, Altenkirch H, Bamborschke S, Baum K, Benecke R, Brück W, Dommasch D, Elias WG, Gass A, Gehlen W, Haas J, Haferkamp G, Hanefeld F, Hartung HP, Heesen C, Heidenreich F, Heitmann R, Hemmer B, Hense T, Hohlfeld R, Janzen RW, Japp G, Jung S, Jügelt E, Koehler J, Kölmel W, König N, Lowitzsch K, Manegold U, Melms A, Mertin J, Oschmann P, Petereit HF, Pette M, Pöhlau D, Pohl D, Poser S, Sailer M, Schmidt S, Schock G, Schulz M, Schwarz S, Seidel D, Sommer N, Stangel M, Stark E, Steinbrecher A, Tumani H, Voltz R, Weber F, Weinrich W, Weissert R, Wiendl H, Wiethölter H, Wildemann U, Zettl UK, Zipp F, Zschenderlein R, Izquierdo G, Kirjazovas A, Packauskas L, Miller D, Koncan Vracko B, Millers A, Orologas A, Panellus M, Sindic CJ, Bratic M, Svraka A, Vella NR, Stelmasiak Z, Selmaj K, Bartosik-Psujik H, Mitosek-Szewczyk K, Belniak E, Mochecka A, Bayas A, Chan A, Flachenecker P, Gold R, Kallmann B, Leussink V, Mäurer M, Ruprecht K, Stoll G, Weilbach FX, Multiple Sclerosis Therapy Consensus Group (2004) Escalating immunotherapy of multiple sclerosis-new aspects and practical application. J Neurol 251:1329–1339

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  28. Fischer JS, Rudick RA, Cutter GR, Reingold SC (1999) The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler 5:244–250

    CAS  PubMed  Google Scholar 

  29. Scherer P, Penner IK, Rohr A, Boldt H, Ringel I, Wilke-Burger H, Burger-Deinerth E, Isakowitsch K, Zimmermann M, Zahrnt S, Hauser R, Hilbert K, Tiel-Wilck K, Anvari K, Behringer A, Peglau I, Friedrich H, Plenio A, Benesch G, Ehret R, Nippert I, Finke G, Schulz I, Bergtholdt B, Breitkopf S, Kaskel P, Reischies F, Kugler J (2007) The Faces Symbol Test, a newly developed screening instrument to assess cognitive decline related to multiple sclerosis: first results of the Berlin Multi-Centre FST Validation Study. Mult Scler 13:402–411

    Article  CAS  PubMed  Google Scholar 

  30. Williams J, O’Rourke K, Hutchinson M, Tubridy N (2006) The Face-Symbol Test and the Symbol-Digit Test are not reliable surrogates for the Paced Auditory Serial Addition Test in multiple sclerosis. Mult Scler 12:599–604

    Article  CAS  PubMed  Google Scholar 

  31. Multiple Sclerosis Council for Clinical Practice Guidelines (1998) Fatigue and multiple sclerosis: evidence-based management strategies for fatigue in multiple sclerosis. Paralysed Veterans of America, Washington DC

    Google Scholar 

  32. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    CAS  PubMed  Google Scholar 

  33. Sullivan MJ, Weinshenker B, Mikail S, Bishop SR (1995) Screening for major depression in the early stages of multiple sclerosis. Can J Neurol Sci 22:228–231

    CAS  PubMed  Google Scholar 

  34. Brown JS, Posner SF, Stewart AL (1999) Urge incontinence: new health-related quality of life measures. J Am Geriatr Soc 47:980–988

    CAS  PubMed  Google Scholar 

  35. Borello-France D, Dusi J, O’Leary M, Misplay S, Okonski J, Leng W, Cannon-Smith T, Chancellor M (2008) Test-retest reliability of the Urge-Urinary Distress Inventory and Female Sexual Function Index in women with multiple sclerosis. Urol Nurs 28:30–35

    PubMed  Google Scholar 

  36. Berg D, Becker G, Zeiler B, Tucha O, Hofmann E, Preier M, Benz P, Jost W, Reiners K, Lange KW (1999) Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 53:1026–1031

    CAS  PubMed  Google Scholar 

  37. Walter U, Behnke S, Eyding J, Niehaus L, Postert T, Seidel G, Berg D (2007) Transcranial brain parenchyma sonography in movement disorders: state of the art. Ultrasound Med Biol 33:15–25

    Article  PubMed  Google Scholar 

  38. Berg D, Roggendorf W, Schröder U, Klein R, Tatschner T, Benz P, Tucha O, Preier M, Lange KW, Reiners K, Gerlach M, Becker G (2002) Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 59:999–1005

    Article  PubMed  Google Scholar 

  39. Godau J, Klose U, Di Santo A, Schweitzer K, Berg D (2008) Multiregional brain iron deficiency in restless legs syndrome. Mov Disord 23:1184–1187

    Article  PubMed  Google Scholar 

  40. Brass SD, Benedict RH, Weinstock-Guttman B, Munschauer F, Bakshi R (2006) Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis. Mult Scler 12:437–444

    Article  CAS  PubMed  Google Scholar 

  41. Liepelt I, Wendt A, Schweitzer KJ, Wolf B, Godau J, Gaenslen A, Bruessel T, Berg D (2008) Substantia nigra hyperechogenicity assessed by transcranial sonography is related to neuropsychological impairment in the elderly population. J Neural Transm 115:993–999

    Article  PubMed  Google Scholar 

  42. Walter U, Krolikowski K, Tarnacka B, Benecke R, Czlonkowska A, Dressler D (2005) Sonographic detection of basal ganglia lesions in asymptomatic and symptomatic Wilson disease. Neurology 64:1726–1732

    Article  CAS  PubMed  Google Scholar 

  43. Maciel P, Cruz VT, Constante M, Iniesta I, Costa MC, Gallati S, Sousa N, Sequeiros J, Coutinho P, Santos MM (2005) Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement. Neurology 65:603–605

    Article  CAS  PubMed  Google Scholar 

  44. Da Cunha C, Wietzikoski EC, Dombrowski P, Bortolanza M, Santos LM, Boschen SL, Miyoshi E (2009) Learning processing in the basal ganglia: a mosaic of broken mirrors. Behav Brain Res 199:157–170

    Article  PubMed  Google Scholar 

  45. Krogias C, Strassburger K, Eyding J, Gold R, Norra C, Juckel G, Saft C, Ninphius D (2010) Depression in Huntington’s Disease correlates with alterations of brainstem raphe depicted by transcranial sonography. J Psychiatry Neurosci (in press)

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  1. Department of Neurology, University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany

    Sebastian Horowski, Uwe K. Zettl, Reiner Benecke & Uwe Walter

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  1. Sebastian Horowski
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Correspondence to Uwe Walter.

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Horowski, S., Zettl, U.K., Benecke, R. et al. Sonographic basal ganglia alterations are related to non-motor symptoms in multiple sclerosis. J Neurol 258, 195–202 (2011). https://doi.org/10.1007/s00415-010-5707-0

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  • DOI: https://doi.org/10.1007/s00415-010-5707-0

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