Metabolic Brain Disease

, Volume 27, Issue 2, pp 217–220 | Cite as

Mimicry between mitochondrial disorder and multiple sclerosis

  • Josef FinstererEmail author
  • Romana Höftberger
  • Claudia Stöllberger
  • Boris Rolinski
Short Communication


Under certain conditions or at certain stages of the disease course, multiple sclerosis (MS) and mitochondrial disorder (MID) may be differential diagnoses and thus may be confused with each other. In a 30 years old female MS was diagnosed at age 16 year upon recurrent sensory disturbances of the right lower leg, an “inflammatory” cerebrospinal fluid, and a cerebral MRI with multiple non-enhancing white matter lesions. Steroids were repeatedly given but because of rapid deterioration treatment was switched to interferon and mitoxantrone, without improvement. Fourteen years after onset the patient additionally presented with a history of rhabdomyolysis, hypothyroidism, ophthalmoparesis, anarthria, tetraspasticity, tetraparesis, and joint contractures. After MID had been diagnosed in her mother she was re-evaluated and elevated resting lactate, axonal polyneuropathy, and empty sella were additionally found. Muscle biopsy revealed myophagy, fat deposition, and type-II predominance, and biochemical investigations showed a deficiency of complex I and IV of the respiratory chain. MID was diagnosed also in the index patient. It is concluded that even if CSF investigations or imaging studies suggest MS, differentials such as MIDs need to be excluded before prescribing medication possibly toxic to a MID. An “inflammatory CSF” may also occur in MIDs.


Multiple sclerosis Metabolic defect Respiratory chain Mitochondrial dysfunction Metabolic myopathy Leucencephalopathy 


  1. Ahlbeck K, Fredriksson K, Rooyackers O, Måbäck G, Remahl S, Ansved T, Eriksson L, Radell P (2009) Signs of critical illness polyneuropathy and myopathy can be seen early in the ICU course. Acta Anaesthesiol Scand 53:717–723PubMedCrossRefGoogle Scholar
  2. Bargalló N, Burrel M, Berenguer J, Cofan F, Buñesch L, Mercader JM (2000) Cortical laminar necrosis caused by immunosuppressive therapy and chemotherapy. Am J Neuroradiol 21:479–484PubMedGoogle Scholar
  3. Barragan-Campos HM, Vallee JN, Lo D, Barrera-Ramírez CF, Argote-Greene M, Sánchez-Guerrero J et al (2005) Brain magnetic resonance imaging findings in patients with mitochondrial cytopathies. Arch Neurol 62:737–742PubMedCrossRefGoogle Scholar
  4. Castro-Gago M, González-Conde V, Fernández-Seara MJ, Rodrigo-Sáez E, Fernández-Cebrián S, Alonso-Martín A, Campos Y, Arenas J, Eirís-Puñal J (1999) Early mitochondrial encephalomyopathy due to complex IV deficiency consistent with Alpers-Huttenlocher syndrome: report of two cases. Rev Neurol 29:912–917PubMedGoogle Scholar
  5. Chinnery PF, Turnbull DM (1999) Mitochondrial DNA and disease. Lancet 354(suppl 1):SI17–S121PubMedGoogle Scholar
  6. D’Aguanno S, Barassi A, Lupisella S (2008) d’eril GM, Del Boccio P, Pieragostino D, Pallotti F, Carelli V, Valentino ML, Liguori R, Avoni P, Bernardini S, Gambi D, Urbani A, Federici G. Differential cerebro spinal fluid proteome investigation of Leber hereditary optic neuropathy (LHON) and multiple sclerosis. J Neuroimmunol 193:156–160PubMedCrossRefGoogle Scholar
  7. Finsterer J (2006) Central nervous system manifestations of mitochondrial disorders. Acta Neurol Scand 114:217–238PubMedCrossRefGoogle Scholar
  8. Geldof K, Ramboer K, Goethals JM, Verhaeghe L (2007) CT and MRI appearance of mitochondrial encephalopathy. JBR-BTR 90:288–289PubMedGoogle Scholar
  9. Harding AE, Sweeney MG, Miller DH, Mumford CJ, Kellar-Wood H, Menard D, McDonald WI, Compston DA (1992) Occurrence of a multiple sclerosis-like illness in women who have a Leber’s hereditary optic neuropathy mitochondrial DNA mutation. Brain 115:979–989PubMedCrossRefGoogle Scholar
  10. Hasselmann O, Blau N, Ramaekers VT, Quadros EV, Sequeira JM, Weissert M (2010) Cerebral folate deficiency and CNS inflammatory markers in Alpers disease. Mol Genet Metab 99:58–61PubMedCrossRefGoogle Scholar
  11. Isohanni P, Linnankivi T, Buzkova J, Lönnqvist T, Pihko H, Valanne L, Tienari PJ, Elovaara I, Pirttilä T, Reunanen M, Koivisto K, Marjavaara S, Suomalainen A (2010) DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis. J Med Genet 47:66–70PubMedCrossRefGoogle Scholar
  12. Kihira T, Kohmoto J, Yoshida S, Hironishi M, Kondo T, Nakao N, Goto Y, Nishino K, Nonaka I (2004) MELAS-like episodes in an adult case with cytochrome c oxidase deficiency. Rinsho Shinkeigaku 44:187–192PubMedGoogle Scholar
  13. Kim J, Lee SK, Kim EY, Kim DI, Lee YM, Lee JS et al (2008) Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects. Eur Radiol 18:1741–1748PubMedCrossRefGoogle Scholar
  14. Kumleh HH, Riazi GH, Houshmand M, Sanati MH, Gharagozli K, Shafa M (2006) Complex I deficiency in Persian multiple sclerosis patients. J Neurol Sci 243:65–69PubMedCrossRefGoogle Scholar
  15. Marie SK, Carvalho AA, Fonseca LF, Carvalho MS, Reed UC, Scaff M (1999) Kearns-Sayre syndrome “plus”. Classical clinical findings and dystonia. Arq Neuropsiquiatr 57:1017–1023PubMedCrossRefGoogle Scholar
  16. Marrie RA, Shoubridge EA, Antel JP, Arnold DL, Chen J, Andermann E, Andermann F (2001) Unusual imaging findings in progressive myoclonus epilepsy. Epilepsia 42:430–432PubMedCrossRefGoogle Scholar
  17. Maruyama S, Yamada T, Ishimoto Y, Hara H, Taniwaki T, Kira J (1998) A case of MELAS showing CSF pleocytosis associated with stroke-like episodes. Rinsho Shinkeigaku 38:641–644PubMedGoogle Scholar
  18. Olsen NK, Hansen AW, Nørby S, Edal AL, Jørgensen JR, Rosenberg T (1995) Leber’s hereditary optic neuropathy associated with a disorder indistinguishable from multiple sclerosis in a male harbouring the mitochondrial DNA 11778 mutation. Acta Neurol Scand 91:326–329PubMedCrossRefGoogle Scholar
  19. Palace J (2009) Multiple sclerosis associated with Leber's Hereditary Optic Neuropathy. J Neurol Sci 286:24–27PubMedCrossRefGoogle Scholar
  20. Parry-Jones AR, Mitchell JD, Gunarwardena WJ, Shaunak S (2008) Leber’s hereditary optic neuropathy associated with multiple sclerosis: Harding’s syndrome. Pract Neurol 8:118–121PubMedCrossRefGoogle Scholar
  21. Pato-Pato A, Cimas-Hernando I, Lorenzo-González JR (2006) Leber’s optic neuropathy: a case report. Rev Neurol 42:22–24PubMedGoogle Scholar
  22. Reszka K, Kolodziejczyk P, Lown JW (1986) Horseradish peroxidase-catalyzed oxidation of mitoxantrone: spectrophotometric and electron paramagnetic resonance studies. J Free Radic Biol Med 2:25–32PubMedCrossRefGoogle Scholar
  23. Robeck S, Stefan H, Engelhardt A, Neundörfer B (1996) Follow-up studies and disorders of endocrinologic function in MELAS syndrome. Nervenarzt 67:465–470PubMedGoogle Scholar
  24. Scaglia F, Wong LJ, Vladutiu GD, Hunter JV (2005) Predominant cerebellar volume loss as a neuroradiologic feature of pediatric respiratory chain defects. Am J Neuroradiol 26:1675–1680PubMedGoogle Scholar
  25. Yiş U, Seneca S, Dirik E, Kurul SH, Ozer E, Cakmakçi H, De Meirleir L (2009) Unusual findings in Leigh syndrome caused by T8993C mutation. Eur J Paediatr Neurol 13:550–552PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Josef Finsterer
    • 1
    • 5
    Email author
  • Romana Höftberger
    • 2
  • Claudia Stöllberger
    • 3
  • Boris Rolinski
    • 4
  1. 1.Danube University KremsKremsAustria
  2. 2.Clinical Institute of NeurologyMedical University ViennaViennaAustria
  3. 3.2. Medical DepartmentKrankenanstaltung RudolfstiftungViennaAustria
  4. 4.Institute of Clinical ChemistryAcademic Hospital München-SchwabingMünchen-SchwabingGermany
  5. 5.ViennaAustria

Personalised recommendations