Patchy Myelinopathies: Pelizaeus-Merzbacher Disease, Cockayne Syndrome, and Others, also Including a Review of Primary Cerebral Mineralizations

  • Reinhard L. Friede


The group of diseases described in this chapter has in common that there are multiple, irregular, patchy myelin defects in the white matter. A morphologic classification of this sort is by necessity provisional, pending identification of etiologic factors. Several of these diseases show, as a second feature, regional mineralization of the cerebral parenchyma. An abstract review of cerebral mineralizations is given in Table 42.1 at the end of this chapter as an aid in differential diagnosis.


Arachnoid Cyst Biotinidase Deficiency Cockayne Syndrome Cerebral Parenchyma Central Nervous System Leukemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aicardi J, Goutières F (1984) A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 15:49–54PubMedCrossRefGoogle Scholar
  2. Amano N, Iwabuchi K, Sakai H, Yagishita S, Itoh Y, Iseki E, Yokoi S, Arai N, Kinoshita J (1987) Nasu-Hakola’s disease (membranous lipodystrophy). Acta Neuropathol (Berl) 74:294–299CrossRefGoogle Scholar
  3. Aurbach GD, Marcus R, Winickoff RN, Epstein EH, Nigra TP (1970) Urinary excretion of 3′,5′-AMP in syndromes considered refractory to parathyroid hormone. Metabolism 19:799–808PubMedCrossRefGoogle Scholar
  4. Babbitt DP, Tang T, Dobbs J, Berk R (1969) Idiopathic familial cerebrovascular ferrocalcinosis (Fahr’s disease) and review of differential diagnosis of intracranial calcification in children. Am J Roentgenol 105:352–358Google Scholar
  5. Bargeton-Farkas E, Edgar GWF (1964) Anatomo-chemical studies on a case of congenital sudanophilic leucodystrophy. Acta Neuropathol (Berl) 3:578–587CrossRefGoogle Scholar
  6. Boller F, Boller M, Gilbert J (1977) Familial idiopathic cerebral calcifications. J Neurol Neurosurg Psychiatry 40:280–285PubMedCrossRefGoogle Scholar
  7. Bourre JM, Bornhofen JH, Araoz CA, Daudu O, Baumann NA (1978) Pelizaeus-Merzbacher disease: brain lipid and fatty acid composition. J Neurochem 30:719–727PubMedCrossRefGoogle Scholar
  8. Bruyn GW, Weenink HR, Bots GTAM, Teepen JLJM, van Wolferen WJA (1985) Pelizaeus-Merzbacher disease. The Löwenberg-Hill type. Acta Neuropathol (Berl) 67:177–189CrossRefGoogle Scholar
  9. Camp DD, Löwenberg K (1941) An American family with Pelizaeus-Merzbacher disease. Arch Neurol Psychiatry 45:261–264Google Scholar
  10. Cockayne EA (1936) Dwarfism with retinal atrophy and deafness. Arch Dis Child 11:1–8PubMedCrossRefGoogle Scholar
  11. Cockayne EA (1946) Dwarfism with retinal atrophy and deafness. Arch Dis Child 21:52–54CrossRefGoogle Scholar
  12. Cockel R, Hill EE, Rushton DI, Smith B, Hawkins CF(1973) Familial steatorrhoea with calcification of the basal ganglia and mental retardation. Q J Med 42:771–783PubMedGoogle Scholar
  13. Copeland DD, Lamb WA, Klintworth GK (1977) Calcification of basal ganglia and cerebellar roof nuclei in mentally defective patient with hidrotic ectodermal dysplasia. Neurology 27:1029–1033PubMedGoogle Scholar
  14. Danowski TS, Lasser EC, Wechsler RL (1960) Calcification of basal ganglia in post-thyroidectomy hypoparathyroidism. Metabolism 9:1064–1065PubMedGoogle Scholar
  15. Dennis JP, Alvord EC Jr (1961) Microcephaly with intracerebral calcification and subependymal ossification: radiologic and clinico-pathologic correlation. Neuropathol Exp Neurol 20:412–426CrossRefGoogle Scholar
  16. D’Hoore E, Gullotta F (1971) Entmarkungsprozeß mit Hirnverkalkungen bei einem mikrocephalen Säugling. Cockayne-Syndrom? Acta Neuropathol (Berl) 18:311–316CrossRefGoogle Scholar
  17. Diezel PB, Huth K (1963) Pelizaeus-Merzbachersche Erkrankung mit familiärem Befall. Dtsch Z Nervenheilkd 184:264–287PubMedCrossRefGoogle Scholar
  18. Diezel PB, Fritsch H, Jakob H (1965) Leukodystrophie mit orthochromatischen Abbaustoffen. Ein Beitrag zur Pelizaeus-Merzbacherschen Krankheit. Virchows Arch [A] 338:371–394Google Scholar
  19. Flament-Durand J, Ketelbant-Balasse P, Maurus R, Regnier R, Spehl M (1975) Intracerebral calcifications appearing during the course of acute lymphocytic leukemia treated with methotrexate and X rays. Cancer 35:319–325PubMedCrossRefGoogle Scholar
  20. Gandolfi A, Horoupian D, Rapin I, DeTeresa R, Hyams V(1984) Deafness in Cockayne’s syndrome: morphological, morphometric, and quantitative study of the auditory pathway. Ann Neurol 15:135–143PubMedCrossRefGoogle Scholar
  21. Grunnet ML, Zimmerman AW, Lewis RA (1983) Ultrastructure and electrodiagnosis of peripheral neuropathy in Cockayne’s syndrome. Neurology 33:1606–1609PubMedGoogle Scholar
  22. Haberland C, Perou M (1977) An unusual malformation of the forebrain and concomitant destructive encephalopathy with calcifications. J Neuropathol Exp Neurol 36:197–213PubMedCrossRefGoogle Scholar
  23. Hallervorden I (1950) Über diffuse symmetrische Kalkablagerungen bei einem Krankheitsbild mit Mikrocephalie und Meningoencephalitis. Arch Psychiatr Nervenkr 184:579–600CrossRefGoogle Scholar
  24. Hammerstein W, Bischof G, Keck E (1982) A tapetoretinal degeneration with symmetrical calcifications of the basal ganglia. A hereditary disease. Eur Neurol 21:249–255PubMedCrossRefGoogle Scholar
  25. Hendin B, DeVivo DC, Torack R, Lell M-E, Ragab AH, Vietti TJ (1974) Parenchymatous degeneration of the central nervous system in childhood leukemia. Cancer 33:468–482PubMedCrossRefGoogle Scholar
  26. Horanyi-Hechst B, Meyer A (1939) Diffuse sclerosis with preserved myelin islands: a pathological report of a case, with a note on cerebral involvement in Raynaud’s disease. J Ment Sci 85:22–28Google Scholar
  27. Jellinger K, Seitelberger F (1969) Pelizaeus-Merzbacher disease. Transitional form between classical and conatal (Seitelberger) type. Acta Neuropathol (Berl) 14:108–117CrossRefGoogle Scholar
  28. Jervis GA (1954) Microcephaly with extensive calcium deposits and demyelination. J Neuropathol Exp Neurol 13:318–329PubMedCrossRefGoogle Scholar
  29. Johnson PC, Nielsen SL, Richardson EP Jr (1980) Enlarged Oligodendroglial nuclei in Cockayne’s syndrome. J Neuropathol Exp Neurol 39:364 (abstr No 83)Google Scholar
  30. Kamoshita S, Igarashi M, Kohno R (1977) Microcephaly with peculiar demyelination mimicking Pelizaeus-Merzbacher disease. Acta Neuropathol (Berl) 40:95–98CrossRefGoogle Scholar
  31. Kramer W (1956) Dysgenetic gliosis of the brain. A case of macrogyria. J Neuropathol Exp Neurol 15:471–484PubMedCrossRefGoogle Scholar
  32. Leech RW, Brumback RA, Miller RH, Otsuka F, Tarone RE, Robbins JH (1985) Cockayne syndrome: clinicopathologic and tissue culture studies of affected siblings. J Neuropathol Exp Neurol 44:507–519PubMedCrossRefGoogle Scholar
  33. Löwenberg K, Hill TS (1933) Diffuse sclerosis with preserved myelin islands. Arch Neurol Psychiatry 29:1232–1245Google Scholar
  34. Lüthy F, Bischoff A (1961) Die Pelizaeus-Merzbachersche Krankheit. Ihre Zuordnung zu den Leukodystrophien, an Hand von drei eigenen familiären Fällen. Acta Neuropathol (Berl) 1:113–134CrossRefGoogle Scholar
  35. Martin JJ, Deberdt R, Philippart M, Van Acker KJ, Hooft C (1971) Peculiar dysmorphic syndrome with orthochromatic leucodystrophy. Discussion of its relationship with Cockayne’s syndrome and Pelizaeus-Merzbacher’s disease. Acta Neuropathol (Berl) 18:224–233CrossRefGoogle Scholar
  36. Matsushita M, Oyanagi S, Hanawa S, Shiraki H, Kosaka K (1981) Nasu-Hakola’s disease (membranous lipodystrophy). A case report. Acta Neuropathol (Berl) 54:89–93CrossRefGoogle Scholar
  37. Mehta L, Trounce JQ, Moore JR, Young ID (1986) Familial calcification of the basal ganglia with cerebrospinal fluid pleocytosis. J Med Genet 23:157–160PubMedCrossRefGoogle Scholar
  38. Melchior JC, Benda CE, Yakovlev PI (1960) Familial idiopathic cerebral calcifications in childhood. Am J Dis Child 99:787–803Google Scholar
  39. Merzbacher L (1910) Eine eigenartige familiär-hereditäre Erkrankungsform (Aplasia axialis extracorticalis congenita). Z Neurol Psychiatr (Originalien) 3:1–138CrossRefGoogle Scholar
  40. Moossy J (1967) The neuropathology of Cockayne’s syndrome. J Neuropathol Exp Neurol 26:654–660PubMedCrossRefGoogle Scholar
  41. Nasu T, Tsukahara Y, Terayama K (1973) Alipid metabolic disease — “membranous lipodystrophy”. An autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. Acta Pathol Jpn 23:539–558PubMedGoogle Scholar
  42. Norman RM, Tingey AH (1966) Syndrome of micrencephaly, strio-cerebellar calcifications, and leucodystrophy. J Neurol Neurosurg Psychiatry 29:157–163CrossRefGoogle Scholar
  43. Norman RM, Tingey AH, Valentine JC, Danby TA(1962) Sudanophil leucodystrophy in a pachygyric brain. J Neurol Neurosurg Psychiatry 25:363–369PubMedCrossRefGoogle Scholar
  44. Norman RM, Tingey AH, Harvey PW, Gregory AM (1966) Pelizaeus-Merzbacher disease: a form of sudanophil leucodystrophy. J Neurol Neurosurg Psychiatry 29:521–529CrossRefGoogle Scholar
  45. Norman RM, Tingey AH, Valentine JC, Hislop HJ (1967) Sudanophil leucodystrophy: a study of inter-sib variation in the form taken by the demyelinating process. J Neurol Neurosurg Psychiatry 30:75–82CrossRefGoogle Scholar
  46. Nyland H, Skre H (1977) Cerebral calcinosis with late onset encephalopathy. Unusual type of pseudo-pseudohypoparathyreoidism. Acta Neurol Scand 56:309–325PubMedCrossRefGoogle Scholar
  47. Ohlsson A, Stark G, Sakati N (1980) Marble brain disease: recessive osteopetrosis, renal tubular acidosis and cerebral calcification in three Saudi Arabian families. Dev Med Child Neurol 22:72–83PubMedCrossRefGoogle Scholar
  48. Otsuka F, Robbins JH (1985) The Cockayne syndrome. An inherited multisystem disorder with cutaneous photosensitivity and defective repair of DNA. Comparison with xeroderma pigmentosum. Am J Dermatopathol 7:387–392PubMedCrossRefGoogle Scholar
  49. Otsuka F, Tarone RE, Cayeux S, Robbins JH (1984) Use of lymphoblastoid cell lines to evaluate the hypersensitivity to ultraviolet radiation of Cockayne syndrome. J Invest Dermatol 82:480–484PubMedCrossRefGoogle Scholar
  50. Pamphlett R, Silberstein P (1986) Pelizaeus-Merzbacher disease in a brother and sister. Acta Neuropathol (Berl) 69:343–346CrossRefGoogle Scholar
  51. Peiffer J, Zerbin-Rüdin E (1963) Zur Variationsbreite der Pelizaeus-Merzbacherschen Krankheit (Zugleich ein Beitrag zur familiären Multiplen Sklerose). Acta Neuropathol (Berl) 3:87–107CrossRefGoogle Scholar
  52. Pelizaeus F (1885) Ueber eine eigenthümliche Form spastischer Lähmung mit Cerebralerscheinungen auf hereditärer Grundlage. (Multiple Sklerose.) Arch Psychiatr Nervenkr 16:698–710CrossRefGoogle Scholar
  53. Price RA, Birdwell DA (1978) The central nervous system in childhood leukemia. III. Mineralizing microangiopathy and dystrophic calcification. Cancer 42:717–728PubMedCrossRefGoogle Scholar
  54. Price RA, Jamieson PA (1975) The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy. Cancer 35:306–318PubMedCrossRefGoogle Scholar
  55. Renier WO, Gabreëls FJM, Hustinx TWJ, Jaspar HHJ, Geelen JAG, Van Haelst UJG, Lommen EJP, Ter Haar BGA (1981) Connatal Pelizaeus-Merzbacher disease with congenital stridor in two maternal cousins. Acta Neuropathol (Berl) 54:11–17CrossRefGoogle Scholar
  56. Reske-Nielsen E, Jensen PK A, Hein-Sorensen O, Abelskov K (1988) Calcification of the central nervous system in a new hereditary neurological syndrome. Acta Neuropathol (Berl) 75:590–596CrossRefGoogle Scholar
  57. Rowlatt U (1969) Cockayne’s syndrome. Report of case with necropsy findings. Acta Neuropathol (Berl) 14:52–61CrossRefGoogle Scholar
  58. Rubinstein LJ, Herman MM, Long TF, Wilbur JR (1975) Disseminated necrotizing leukoencephalopathy: a complication of treated central nervous system leukemia and lymphoma. Cancer 35:291–305PubMedCrossRefGoogle Scholar
  59. Sarnat HB, Adelman LS (1973) Perinatal sudanophilic leukodystrophy. Am J Dis Child 125:281–285PubMedGoogle Scholar
  60. Schneck L, Adachi M, Volk BW (1971) Congenital failure of myelinization: Pelizaeus-Merzbacher disease? Neurology 21:817–824PubMedGoogle Scholar
  61. Schulz PE, Weiner SP, Belmont JW, Fishman MA (1988) Basal ganglia calcification in a case of biotinidase deficiency. Neurology 38:1326–1328PubMedGoogle Scholar
  62. Seitelberger F (1954) Die Pelizaeus-Merzbachersche Krankheit. Klinisch-anatomische Untersuchung zum Problem ihrer Stellung unter den diffusen Sklerosen. Wien Z Nervenheilkd 9:228–289Google Scholar
  63. Seitelberger F (1970) Pelizaeus-Merzbacher disease. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, Vol 10. North Holland, Amsterdam, pp 150–202Google Scholar
  64. Smits MG, Gabreëls FJM, Renier WO, Joosten EMG, Gabreëls-Festen AAWM, ter Laak HJ, Pinckers AJL, Hombergen GCJ, Notermans SLM, Thijssen HOM (1982) Peripheral and central myelinopathy in Cockayne’s syndrome. Report of 3 siblings. Neuropediatrics 13:161–167PubMedCrossRefGoogle Scholar
  65. Smits MG, Gabreëls FJM, Thijssen HOM, ‘t Lam RL, Notermans SLH, ter Haar BGA, Prick JJ (1983) Progressive idiopathic strio-pallido-dentate calcinosis (Fahr’s disease) with autosomal recessive inheritance. Report of three siblings. Eur Neurol 22:58–64PubMedCrossRefGoogle Scholar
  66. Soffer D, Grotsky HW, Rapin I, Suzuki K (1979) Cockayne syndrome: unusual neuropathological findings and review of the literature. Ann Neurol 6:340–348PubMedCrossRefGoogle Scholar
  67. Sourander P (1970) A new entity of phacomatosis: B. Brain lesions (sclerosing leukoencephalopathy). Acta Pathol Microbiol Scand, Sect. A & B, Suppl 215:44Google Scholar
  68. Spielmeyer W (1923) Der anatomische Befund bei einem zweiten Fall von Pelizaeus-Merzbacherscher Krankheit. Zentralbl Neurol Psychiatr (Referate) 32:203Google Scholar
  69. Statz A, Boltshauser E, Schinzel A, Spiess H (1981) Computed tomography in Pelizaeus-Merzbacher disease. Neuroradiology 22:103–105PubMedCrossRefGoogle Scholar
  70. Tanaka J (1980) Leukoencephalopathic alteration in membranous lipodystrophy. Acta Neuropathol (Berl) 50:193–197CrossRefGoogle Scholar
  71. Thulin B, McTaggart D, Neubuerger KT (1968) Demyelinating leukodystrophy with total cortical cerebellar atrophy. Arch Neurol 18:113–122PubMedGoogle Scholar
  72. Troost D, van Rossum A, Pires JV, Willemse J (1984) Cerebral calcifications and cerebellar hypoplasia in two children: clinical, radiologic and neuropathological studies — a separate neurodevelopmental entity. Neuropediatrics 15:102–109PubMedCrossRefGoogle Scholar
  73. Ulrich J, Herschkowitz N (1977) Seitelberger’s connatal form of Pelizaeus-Merzbacher disease. Case report, clinical, pathological and biochemical findings. Acta Neuropathol (Berl) 40:129–136CrossRefGoogle Scholar
  74. Vos A, Gabreëls-Festen A, Joosten E, Gabreëls F, Renier W, Mullaart R (1983) The neuropathy of Cockayne syndrome. Acta Neuropathol (Berl) 61:153–156CrossRefGoogle Scholar
  75. Watanabe I, McCaman R, Dyken P, Zeman W(1969) Absence of cerebral myelin sheaths in a case of presumed Pelizaeus-Merzbacher disease. Electron microscopic and biochemical studies. J Neuropathol Exp Neurol 28:243–256PubMedCrossRefGoogle Scholar
  76. Watanabe I, Patel V, Goebel HH, Siakotos AN, Zeman W, DeMyer W, Schroder Dyer J (1973) Early lesion of Pelizaeus-Merzbacher disease: electron microscopic and biochemical study. J Neuropathol Exp Neurol 32:313–333PubMedCrossRefGoogle Scholar
  77. Weerdt CJ de, Hooghwinkel GJM (1977) Congenital retarded myelinization in a new-born child with infantile spasms. Clin Neurol Neurosurg 79:143–150Google Scholar
  78. Wicke R (1938) Ein Beitrag zur Frage der familiären diffusen Sklerosen einschließlich der Pelizaeus-Merzbacherschen Krankheit und ihrer Beziehung zur amaurotischen Idiotie. Z Neurol Psychiatr 162:741–766CrossRefGoogle Scholar
  79. Willard HF, Riordan JR (1985) Assignment of the gene for myelin proteolipid protein to the X chromosome: implications for X-linked myelin disorders. Science 230:940–942PubMedCrossRefGoogle Scholar
  80. Witter B, Debuch H, Klein H (1980) Lipid investigation of central and peripheral nervous system in connatal Pelizaeus-Merzbacher’s disease. J Neurochem 34:957–962PubMedCrossRefGoogle Scholar
  81. Yokoi S, Amano N, Hanawa H, Isoyama K, Ishikawa A, Ogino T (1985) Postnatal sudanophilic leukodystrophy in two siblings. Acta Neuropathol (Berl) 67:103–113CrossRefGoogle Scholar
  82. Young EF, Courville CB (1961) “Familial” central cerebral calcification in infancy. Report of two cases in siblings. Bull Los Angeles Neurol Soc 26:198–208PubMedGoogle Scholar
  83. Zeman W, Demyer W, Fallis HF (1964) Pelizaeus-Merzbacher disease. A study in nosology. J Neuropathol Exp Neurol 23:334–354PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Reinhard L. Friede
    • 1
  1. 1.Zentrum Neurologische Medizin, Abteilung NeuropathologieGeorg-August-Universität GöttingenGöttingenGermany

Personalised recommendations