APPENDIX e-2: Reasons why studies were excluded from the review

Reason studies were judged to be ineligible

/

No of studies

/

Reference

Ineligible studies from the treated series part of the review
EEG or other short term measurement study/Response to drug as part of the diagnostic process / 7 / 1,2,3,4,5,6,7
No therapeutic intervention/Pre diagnosis treatment / 4 / 8,9[*],10[†],11[‡]
Laboratory study/Animal model / 5 / 12,13,14,15,16
Review article/Comment on other studies / 12 / 17,18,19,20,21,22,23,24,25,26,27,28
News article / 9 / 29,30,31,32,33,34,35,36,37
Not CJD, not Prion disease / 1 / 38
Other / 1 / 39
Ineligible studies from the untreated series part of the review
Insufficient quantitative data: Incidence only / 8 / 40,41,42,43,44,45,46,47
No usable quantitative data: genetic studies / 10 / 48,49,50,51,52,53,54,55,56,57
Insufficient quantitative data: Prognostic analysis/Risk factor study / 5 / 58,59,60,61,62
Single Case[§] / 18 / 63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80
Review article/Summary of other studies/Commentary / 15 / 81,82,83,84,85,86,87,88,89,90,91,92,93,94,95
Pre-1966 / 1 / 96
Not CJD, not prion disease / 4 / 97,98,99,100
Kuru / 5 / 101,102,103,104,105
Other / 2 / 106,107

References

1. Nomura, E., Harada, T., Kurokawa, K.et al. Creutzfeldt-Jakob disease associated with autonomic nervous system dysfunction in the early stage. Internal Medicine 1997;36:492-496

2. Clarke, C. E., Bamford, J. M., and House, A. Dyskinesia in Creutzfeldt-Jakob disease precipitated by antidepressant therapy. Movement Disorders 1992;7:86-87

3. Khurana, R. K. and Garcia, J. H. Autonomic dysfunction in subacute spongiform encephalopathy. Archives of Neurology 1981;38:114-117

4. Roccatagliata, G., Primavera, A., and Albano, C. Effect of trazodone on massive rhythmic spontaneous myoclonus. Rivista di Neurologia 1979;49:99-107

5. McCutchen, C. B. , Vignaendra, V., and Chatrian, G. E. Electrographic and clinical effects of intracarotid sodium amobarbital on bilateral myoclonic status epilepticus. Neurology 1977;27:252-256

6. Elliott, F., Gardner-Thorpe, C., Barwick, D.D., and Foster, J. B. Jakob-Creutzfeldt disease. Modification of clinical and electroencephalographic activity with methylphenidate and diazepam. Journal of Neurology, Neurosurgery & Psychiatry 1974;37:879-887

7. Gaches, J., Supino-Viterbo, V., and Oughourlian, J. M. Contribution to the electro-clinical study of the effect of diazepam in Creutzfeldt-Jakob disease. Semaine des Hopitaux 1972;48:1601-1606

8. Roth, A. M., Keltner, J. L., Ellis, W. G., and Martins-Green, M. Virus-simulating structures in the optic nerve head in Creutzfeldt-Jakob disease. American Journal of Ophthalmology 1979;87:827-833

9. Rees, J. H., Smith, S. J., Kullman, D. M., Hirsch, N. P., and Howard, R. S. Creutzfeldt-Jakob disease presenting as complex partial status epilepticus: a report of two cases. Journal of Neurology, Neurosurgery & Psychiatry 1999;66:406-407

10. Fernandez-Torre, J. L., Solar, D. M., Astudillo, A.et al. Creutzfeldt-Jakob disease and non-convulsive status epilepticus: a clinical and electroencephalographic follow-up study. Clinical Neurophysiology 2004;115:316-319

11. Cortelli, P., Parchi, P., Contin, M.et al. Cardiovascular dysautonomia in fatal familial insomnia. Clinical Autonomic Research 1991;1:15-21

12. McKenzie, D., Kaczkowski, J., Marsh, R., and Aiken, J. Amphotericin B delays both scrapie agent replication and PrP-Res accumulation early in infection. Journal of Virology 1994;68:7534-7536

13. Farquhar, C., Dickinson, A., and Bruce, M. Prophylactic potential of pentosan polyphosphate in transmissible spongiform encephalopathies. Lancet 1999;353:117

14. Shaked, G. M., Engelstein, R., Avraham, I., Rosenmann, H., and Gabizon, R. Valproic acid treatment results in increased accumulation of prion proteins. Annals of Neurology 2002;52:416-420

15. Mangé, A., Nishida, N., Milhavet, O.et al. Amphotericin B inhibits the generation of scrapie isoform of the prion protein in infected cultures. Journal of Virology 2000;74:3135-3140

16. Manuelidis, L., Fritch, W., and Zaitsev, I. Dapsone to delay symptoms in Creutzfeldt-Jakob disease. Lancet 1998;352:456

17. MacLeod, M. A. Potential treatments and treatment strategies in Creutzfeldt-Jakob disease. Idrugs 2003;6:345-350

18. Norris, F. H. Jr. Amantadine in Jakob-Creutzfeldt disease. BMJ 1972;2:349

19. Forster, C. EEG changes in Jakob-Creutzfeldt's disease under the influence of diazepam. Electroencephalography & Clinical Neurophysiology 1970;29:218

20. Sander, J. W. and Duncan , J. S. Valproic acid and prion proteins. Annals of Neurology 2003;53:688-689

21. Braunholtz, D. and Harris, J. Quinacrine in possible or probable CJD: if you had suspected CJD would you be indifferent between placebo and quinacrine. BMJ 2002;324:239

22. Cooper, E. Quinacrine in possible or probable CJD: it is blinded investigators, not patients, who must be in equipoise over treatment. BMJ 2002;324:239

23. Adjou, K. T. and Seman, M. What are the prospects for pharmacological treatment of prion disease?. Therapie 2002;57:123-127

24. Calissano, M., Petraroli, R., and Pocchiari, M. Therapeutical approaches to transmissible spongiform encephalopathies (TSE): the case of amphotericin-B. Journal of Biological Regulators & Homeostatic Agents 1996;10:69-71

25. Oken, R. J. and McGeer, P. L. Human prion diseases: possible new directions in prophylaxis and therapy. Medical Hypotheses 1995;44:167-168

26. Bendheim, P. E. The human spongiform encephalopathies. Neurologic Clinics 1984;2:281-298

27. Korth, C., May, B. C. H., Cohen, F. E., and Prusiner, S. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proceedings of the NationalAcademy of Sciences of the United States of America. 2001;98:9836-9841

28. Griffiths, P. D. Preparing to treat prions. Reviews in Medical Virology 2002 ;12:1-3

29. Follette, P. New perspectives for prion therapeutics meeting. Prion disease treatment's early promise unravels. Science 2003;299:191-192

30. Dyer, C. Second vCJD patient to receive experimental treatment. BMJ 2003;327:886

31. Gould, M. Medicines committee felt unable to recommend use of pentosan polyphosphate in vCJD. BMJ 2003;327:770

32. Mayor, S. Small improvement seen in teenager with vCJD. BMJ 2003;327:765

33. Dyer, O. Family finds hospital willing to give experimental CJD treatment. BMJ 2003;326:8

34. Josefson, D. Drugs for malaria and psychosis may offer hope to people with CJD. BMJ 2001;323:416

35. Giles, J. Rapid drug trial offers hope to CJD patients. Nature 2003;426:487

36. Pincock, S. Experimental treatment may show promise for vCJD. Lancet 2003;362:1130

37. Love, R. Old drugs to treat new variant Creutzfeldt-Jakob disease. Lancet 2001;358:563

38. Utsumiya, K., Arakawa, R., Fujimoto, S., Ueyama, H., and Kumamoto, T. A case of steroid-responsive encephalopathy with positive 14-3-3 protein of the cerebrospinal fluid clinically resembling Creutzfeldt-Jakob disease. Rinsho Shinkeigaku - Clinical Neurology 2004;44:618-622

39. Nalbandian, R. M., Murayama, M., and Henry, R. L. Restoration of phagocytosis and oxidative metabolism by Piracetam in failing human neutrophils: a qualitative assessment. Clinical Immunology & Immunopathology 1983;28:155-169

40. Alperovitch, A. , Brown, P., Weber, T.et al. Incidence of Creutzfeldt-Jakob disease in Europe in 1993. Lancet 1994;343:918

41. Cousens, S. N., Zeidler, M., Esmonde, T. Fet al. Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970-96. BMJ 1997;315:389-395

42. Farmer, P. M., Kane, W. C., and Hollenberg-Sher, J. Incidence of Creutzfeldt-Jakob disease in Brooklyn and Staten Island. New England Journal of Medicine 1978;298:283-284

43. Mad'ar, R., Maslenova, D., Ranostajova, K., Straka, S., and Baska, T. Analysis of unusual accumulation of Creutzfeldt-Jakob disease cases in Orava and Liptov regions (northern Slovak focus) 1983-2000. Central European Journal of Public Health 2003;11:19-22

44. Mills, J. L., Schonberger, L. B., Wysowski, D. K.et al. Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients. The Journal of Pediatrics 2004;144:430-436

45. Mollenhauer, B. , Zerr, I., Ruge, D.et al. Epidemiology and clinical symptomatology of Creutzfeldt-Jakob disease. Deutsche Medizinische Wochenschrift 2002;127:312-317

46. Stratton, E. Creutzfeldt-Jakob disease: the Canadian situation. CMAJ : Canadian Medical Association Journal 1997;157:1405-1408

47. Will, R. G., Alperovitch, A., Poser, S.et al. Descriptive epidemiology of Creutzfeldt-Jakob disease in six European countries, 1993-1995. EU collaborative study group for CJD. Annals of Neurology 1998;43:763-767

48. Brown, P., Cervenakova, L., Goldfarb, L. G.et al. Iatrogenic Creutzfeldt-Jakob disease: an example of the interplay between ancient genes and modern medicine. Neurology 1994a;44:291-293

49. Collinge, J., Palmer, M. S., and Dryden, A. J. Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 1991;337:1441-1442

50. Goldfarb, L. G. , Korczyn, A. D., Brown, P., Chapman, J., and Gajdusek, D. C. Mutation in codon 200 of scrapie amyloid precursor gene linked to Creutzfeldt-Jakob disease in sephardic Jews of Libyan and non-Libyan origin. Lancet 1990;336:637-638

51. Goldfarb, L. G. , Mitrova, E., Brown, P., Toh, B. K., and Gajdusek, D. C. Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt-Jakob disease in Slovakia. Lancet 1990;336:514-515

52. Goldgaber, D., Goldfarb, L. G., Brown, P.et al. Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker's syndrome. Experimental Neurology 1989;106:204-206

53. Kitamoto, T., Ohta, M., Doh-ura, K.et al. Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome. Biochemical and Biophysical Research Communications 1993;191:709-714

54. Kovacs, G. G., Trabattoni, G., Hainfellner, J. A.et al. Mutations of the prion protein gene phenotypic spectrum. Journal of Neurology 2002;249:1567-1582

55. Miyazono, M., Kitamoto, T., Doh-ura, K., Iwaki, T., and Tateishi, J. Creutzfeldt-Jakob disease with codon 129 polymorphism (valine): a comparative study of patients with codon 102 point mutation or without mutations. Acta Neuropathologica 1992;84:349-354

56. Tagliavini, F., Prelli, F., Porro, M.et al. Amyloid fibrils in Gerstmann-Straussler-Scheinker disease (Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele. Cell 1994;79:695-703

57. Nakagawa, Y., Kitamoto, T., Furukawa, H., Ogomori, K., and Tateishi, J. Allelic variation of apolipoprotein e in Japanese sporadic Creutzfeldt-Jakob disease patients. Neuroscience Letters 1995;187:209-211

58. Ladogana, A., Puopolo, M., Almonti, S.et al. Analysis of the factors influencing survival in human transmissible spongiform encephalopathies. Presented at Prion diseases: from basic research to intervention concepts. Oct 8-10, 2003; Munich. Abstract PG-30:

59. Wientjens, D. P., Davanipour, Z., Hofman, A.et al. Risk factors for Creutzfeldt-Jakob disease: a reanalysis of case-control studies. Neurology 1996;46:1287-1291

60. Brooke, F. J., Boyd, A., Klug, G. M., Masters, C. L., and Collins, S. J. Lyodura use and the risk of iatrogenic Creutzfeldt-Jakob disease in Australia. Medical Journal of Australia 2004;180:177-181

61. van Duijn, C. M., Delasnerie-Laupretre, N., Masullo, C.et al. Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95. European Union (EU) collaborative study group of Creutzfeldt-Jakob disease (CJD). Lancet 1998;351:1081-1085

62. Zerr, I., Brandel, J. P., Masullo, C.et al. European surveillance on Creutzfeldt-Jakob disease: a case-control study for medical risk factors. Journal of Clinical Epidemiology 2000;53:747-754

63. Anderson, J. R. , Allen, C. M. C., and Weller, R. O. Creutzfeldt-Jakob disease following human pituitary-derived growth hormone administration . Neuropathology & Applied Neurobiology 1990;16:534

64. Chapman, J., Arlazoroff, A., Goldfarb, L. G.et al. Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200 (Lys) mutation. Neurology 1996;46:758-761

65. Clavel, M. and Clavel, P. Creutzfeldt-Jakob disease transmitted by dura mater graft. European Neurology 1996;36:239-240

66. Collinge, J., Brandner, S., Kennedy, A.et al. A 38-year-old man with a 9 month history of neurological and cognitive impairment. Lancet Neurology 2003;2:189-194

67. Delasnerie-Laupretre, N., Poser, S., Pocchiari, M., Wientjens, D. P., and Will, R. Creutzfeldt-Jakob disease in Europe. Lancet 1995 ;346:898

68. Deslys, J. P., Lasmezas, C. I., Streichenberger, N.et al. New variant Creutzfeldt-Jakob disease in France. Lancet 1997;349:30-31

69. Ehrat, C. h. and Maire, P. Rapidly progressing dementia. Verified sporadic Creutzfeldt-Jakob disease (CJD). Schweizerische Rundschau fur Medizin Praxis 2002;91:750-752

70. Gaches, J., Supino-Viterbo, V., and Foncin, J. F. Association of Alzheimer's disease and Creutzfeldt-Jakob's disease. Acta Neurologica Belgica 1977;77:202-212

71. Goldhammer, Y., Gabizon, R., Meiner, Z., and Sadeh, M. An Israeli family with Gerstmann-Straussler-Scheinker disease manifesting the codon 102 mutation in the prion protein gene. Neurology 1993;43:2718-2719

72. Heldt, N., Boellaard, J. W., Brown, P.et al. Gerstmann-Straussler-Scheinker disease with A117V mutation in a second French-Alsatian family. Clinical Neuropathology 1998;17:229-234

73. Mastrianni, J. A., Curtis, M. T., Oberholtzer, J. C.et al. Prion disease (PrP-A117V) presenting with ataxia instead of dementia. Neurology 1995;45:2042-2050

74. Nagayama, M., Shinohara, Y., Furukawa, H., and Kitamoto, T. Fatal familial insomnia with a mutation at codon 178 of the prion protein gene: first report from Japan. Neurology 1996;47:1313-1316

75. Nicholl, D., Windl, O., de Silva, R.et al. Inherited Creutzfeldt-Jakob disease in a British family associated with a novel 144 base pair insertion of the prion protein gene. Journal of Neurology, Neurosurgery & Psychiatry 1995;58:65-69

76. Pocchiari, M., Masullo, C., Salvatore, M., Genuardi, M., and Galgani, S. Creutzfeldt-Jakob disease after non-commercial dura mater graft.. Lancet 1992;340:614-615

77. Reder, A. T., Mednick, A. S., Brown, P.et al. Clinical and genetic studies of fatal familial insomnia. Neurology 1995;45:1068-1075

78. Reuber, M., Al-Din, A. S., Baborie, A., and Chakrabarty, A. New variant Creutzfeldt-Jakob disease presenting with loss of taste and smell. Journal of Neurology, Neurosurgery & Psychiatry 2001;71:412-413

79. Vallat, J. M., Dumas, M., Corvisier, N.et al. Familial Creutzfeldt-Jakob disease with extensive degeneration of white matter. Ultrastructure of peripheral nerve. Journal of the Neurological Sciences 1983;61:261-275

80. Zarranz, J. J., Rivera Pomar, J. M., and Salisachs, P. Kuru plaques in the brain of two cases with Creutzfeldt-Jakob disease. A common origin for the two diseases? Journal of the Neurological Sciences 1979;43:291-300

81. Pocchiari, M., Puopolo, M., Croes, E. A.et al. Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Brain 2004;127:2348-2359

82. Belay, E. D., Maddox, R. A., Gambetti, P., and Schonberger, L. B. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States. Neurology 2003;60:176-181

83. Brown, P., Preece, M., Brandel, J. P.et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000;55:1075-1081

84. Budka, H. Fatal familial insomnia around the world. Introduction. Brain Pathology 1998;8:553

85. Frasier, S. D. and Foley, T. P. Jr. Clinical review 58: Creutzfeldt-Jakob disease in recipients of pituitary hormones. Journal of Clinical Endocrinology and Metabolism 1994;78:1277-1279

86. Gambetti, P., Parchi, P., Petersen, R. B., Chen, S. G., and Lugaresi, E. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: clinical, pathological and molecular features. Brain Pathology 1995;5:43-51

87. Gambetti, P. and Lugaresi, E. Conclusions of the symposium. Brain Pathology 1998;8:571-575

88. Goldfarb, L. G. , Petersen, R. B., Tabaton, M.et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science 1992;258:806-808

89. Groenewold, M. R. Analysis for space-time clustering of CJD cases, Kentucky, 1988-1997. Journal of the Kentucky Medical Association 2004;102:163-170

90. Masters, C. L., Gajdusek, D. C., and Gibbs, C. J. Jr. The familial occurrence of Creutzfeldt-Jakob disease and Alzheimer's disease. Brain 1981;104:535-558

91. Reingold, A. and et al. From the centers for disease control and prevention. Surveillance for Creutzfeldt-Jakob disease - United States. JAMA 1996;276:938-939

92. Worrall, B. B., Rowland, L. P., Chin, S. S., and Mastrianni, J. A. Amyotrophy in prion diseases. Archives of Neurology 2000;57:33-38

93. Horton, R. nvCJD: after the hype, some real data.. Lancet 1997;349:820

94. Preusser, M., Gelpi, E., Hainfellner, J. A., and Budka, H. Ten years of EC-funded concerted actions on the neuropathology of prion disease: report on the final scientific meeting (31 October-2 November 2003, Baden near Vienna, Austria). Neuropathology & Applied Neurobiology 2004;30:308-310

95. Brown, P., Goldfarb, L. G., Gibbs, C. J. Jr, and Gajdusek, D. C. The phenotypic expression of different mutations in transmissible familial Creutzfeldt-Jakob disease. European Journal of Epidemiology 1991;7:469-476

96. Bubelis, I., Desai, A. D., and Deshpande, D. Infantile Jakob-Creutzfeldt disease. Neurology India 1966;14:53-56

97. Goujard, J., Entat, M., Maillard, F.et al. Human pituitary growth hormone (hGH) and Creutzfeldt-Jakob disease: results of an epidemiological survey in France, 1986. International Journal of Epidemiology 1988;17:423-427

98. Orlova, E. G. and Salimova, L. V. Diagnosis and course of Creutzfeldt-Jakob disease (clinico-pathologoanatomic parallels). Zhurnal Nevropatologii i Psikhiatrii Imeni S - S - Korsakova 1984;84:1804-1809

99. Wada, Y., Yamamoto, T., Kita, Y., Fukunishi, S., and Ashida, K. An autopsy case of encephalopathy associated with small cell carcinoma of the stomach with nonconvulsive status epilepticus resembling Creutzfeldt-Jakob disease. No to Shinkei - Brain & Nerve 2003;55:423-428

100. Wientjens, D. P., Rikken, B., Wit, J. M., Hofman, A., and Stricker, B. H. A nationwide cohort study on Creutzfeldt-Jakob disease among human growth hormone recipients. Neuroepidemiology 2000;19:201-205

101. Cervenakova, L., Goldfarb, L. G., Garruto, R.et al. Phenotype-genotype studies in Kuru: implications for new variant Creutzfeldt-Jakob disease. Proceedings of the NationalAcademy of Sciences of the United States of America. 1998;95:13239-13241

102. Hornabrook, R. W. and Field, E. J. Clinical and pathological findings in Kuru. Lancet 1969;1:576

103. Hornabrook, R. W. Kuru - a subacute cerebellar degeneration. The natural history and clinical features. Brain 1968;91:53-74

104. Kompoliti, K., Goetz, C. G., Gajdusek, D. C., and Cubo, E. Movement disorders in Kuru. Movement Disorders 1999;14:800-804

105. Prusiner, S. B., Gajdusek, D. C., and Alpers, M. P. Kuru with incubation periods exceeding two decades. Annals of Neurology 1982;12:1-9

106. Goldman, J. S. , Miller, B. L., Safar, J.et al. When sporadic disease is not sporadic: the potential for genetic etiology. Archives of Neurology 2004;61:213-216

107. Larner, A. J. and Doran, M. Prion disease at a regional neuroscience centre: retrospective audit. Journal of Neurology, Neurosurgery & Psychiatry 2004;75:1789-1790

[*] one patient also treated for depression and epilepsy pre-diagnosis of CJD

[†] patient also treated for epilepsy pre-diagnosis of CJD

[‡] patient also treated for epilepsy

[§] As stated in the protocol single case studies were not included in the untreated patient series because only a very small proportion of cases are written up and published and those that are published may be selected because they are atypical rather than representative