The neuropathology of encephalitis lethargica

Abstract

Precise knowledge of the histological substrate of epidemic encephalitis, it appears to me, is indispensable not only for understanding the clinical presentation during the acute phase and the entire course of the disease, but also for understanding the severe after-effects. Heinrich Pette, 1942.

Appendix: Overview of major encephalitis lethargica neuropathological reports

Table 1 These publications are illustrated unless marked with an asterisk. Abbreviations: AT Austria, CA Canada, CH Switzerland, CZ Czechoslovakia, DE Germany, FR France, GB Great Britain, HU Hungary, IT Italy, SU USSR, US USA; w weeks, m months; —: information not provided in report

Notes

• 1. Cf. Schaffer 1915.

• 2. Jakob 1923, p. v.

• 3. Konschegg & Ott 1940.

• 4. In his influential nosography (1763) Boissier de Sauvages described a number of disorders including elements of encephalitis as Comata, “in which the principal symptom is the suspension of all the senses, not infrequently also of the mind (imaginatio)”; amongst the specific forms were the suggestively titled Lethargicus cephaliticus and Cephalitis epidemica, neither of which, however, were relevant to EL.

• 5. Jourdan 1815.

• 6. Jourdan 1812.

• 7. Cf. Bouillaud 1825.

• 8. Friedrich Berndt (Greifswald) included an unrelated “febris lethargica” in his nosology of fever (1830, pp. 855–866), as well as a separate Encephalitis lethargica (without further explanation) alongside E. cephalalgica and E. phrenitica in his general nosology (1833, p. 79).

• 9. Wernicke 1881, pp. 229–242.

• 10. Strümpell 1890; Leichtenstern 1892.

• 11. Wickman 1911, pp. 860–864.

• 12. Schilder 1912.

• 13. Redlich 1917.

• 14. Major contemporary reviews: Chartier 1907; Oppenheim & Cassirer 1907; Vogt 1912.

• 15. Gerlach 1929.

• 16. Rößle 1923.

• 17. Contemporary reviews: Aschoff 1921, 1922; Lubarsch 1921a; Fischer-Wasels 1924; Askanazy 1929. See also presentations and discussion at 1923 meeting of the Deutsche Pathologische Gesellschaft (Verhandlungen, 19, 3–143).

• 18. von Monakow 1922.

• 19. von Monakow 1922.

• 20. von Economo 1929a, pp. 100–101.

• 21. von Economo 1917/18, p. 303.

• 22. Häuptli 1921.

• 23. German pathologists in the 1920s rarely employed the term ‘neuron’, preferring ‘Ganglienzelle’ for grey matter neurons (often referring specifically to the cell body), while in other countries both ‘ganglion cell’ and ‘nerve cell’ were employed. I have used ‘ganglion cell’ here to underscore that the original reference was to the cell body, not its projections.

• 24. Spielmeyer 1920a.

• 25. von Economo 1917/18, pp. 300–321; see also von Economo 1929a, pp. 100–126.

• 26. As, for instance, in the hyperacute EL cases reviewed in 2009 by Anderson and colleagues.

• 27. Marinesco 1918a.

• 28. Marinesco 1918b.

• 29. Tobler 1920.

• 30. van Bogaert 1958.

• 31. van Boeckel et al. 1923, p. 202.

• 32. Buzzard & Greenfield 1920; Guizzetti & Giugni 1920. An exception: Auerbach 1920.

• 33. Mackenzie 1927.

• 34. Buzzard & Greenfield 1921, p. 204.

• 35. Globus & Strauss 1922.

• 36. Bassoe & Hassin 1919.

• 37. Hurst 1936.

• 38. For example: Adolf & Spiegel 1920; Jaffé 1920.

• 39. Stern 1928, p. 286. see also Siegmund 1921.

• 40. For example: Rosenfeld 1924.

• 41. Högner 1927. Similar: Fulton & Bailey 1929.

• 42. Gamna 1921a; Stern 1936, pp. 402f.

• 43. Economo 1929a, p. 87. See also van Bogaert 1958.

• 44. Luzzatto & Rietti 1920.

• 45. Wilson 1954.

• 46. Klarfeld 1922.

• 47. von Economo 1929a, pp. 118f.

• 48. Stern 1928, p. 308.

• 49. von Economo 1929a, pp. 199f.

• 50. Stern 1936, pp. 410f.

• 51. Marie & Trétiakoff 1918.

• 52. Groß 1923.

• 53. See, for example, Gerlach-W 1920; Häuptli 1921; Creutzfeldt 1923.

• 54. Stern 1936, p. 402.

• 55. Including von Economo 1920; Boyd 1920/21; MacNalty 1922.

• 56. Spatz 1930a, p. 239.

• 57. “Stimulated form of leukocyte with relatively large amount of cytoplasm and thereby seemingly small nucleus” (Dornblüth 1927). Now also termed ‘plasmocytes’ or ‘effector B cells’: ‘antibody factories’ that secrete large amounts of antibody directed at a single antigen.

• 58. Virchow–Robin spaces are particularly prominent in the basal ganglia, cerebral peduncle, and mesencephalon–diencephalon border region: see Gess et al. 2010.

• 59. During the 1920s, both the origin and classification of white blood cells were unsettled questions at this time; contemporary reviews: Sabin 1922; Schilling 1937.

• 60. Häuptli 1921; Herzog 1921a; Wohlwill 1924.

• 61. Cf. Marinescu-Baloi 1926a.

• 62. See, for example, Lhermitte 1922; Stern 1928, p. 287; Spatz 1930a, pp. 240 f; see also Marcora 1921; Sepp 1925.

• 63. von Economo 1929a, p. 109; Oberndorfer 1919; Achard & Foix 1920; Herxheimer 1920; Häuptli 1921.

• 64. Pette 1942, p. 160.

• 65. Klarfeld 1922.

• 66. Klarfeld 1922.

• 67. Oberndorfer 1919.

• 68. Stern 1936, p. 404.

• 69. Spielmeyer 1920a; Oberndorfer 1919; Stern 1919/20; Luzzato & Rietti 1921; Mittasch 1921; see also Spatz 1930a, pp. 241–243.

• 70. Wimmer & Neel 1928.

• 71. Obituaries and bibliography: Hassler 1969; Scholz 1969; Max-Planck-Institut für Hirnforschung 1971.

• 72. Bielschowsky commented in 1910 that, for clinicians, “inflammation is a complex concept in which the histologic aspect is not seldom subordinated to the clinical and etiologic elements.”

• 73. Such as Schröder 1922.

• 74. Spatz 1930a, pp. 165f.

• 75. Stern 1919/20; see also Lüthy & Walthard 1928; p. 629 of this volume.

• 76. For example, Klarfeld 1922.

• 77. For the history of earlier consideration of the cells that Río Hortega described, see introduction to del Río Hortega 1932; Barron 1995; Rezaie & Male 2002; Kettenmann & Verkhratsky 2008; Webster & Åström 2009; Foley 2018.

• 78. del Río Hortega 1919, 1925a,b, 1932.

• 79. del Río-Hortega 1939.

• 80. del Río-Hortega 1939.

• 81. Cf. Askanazy 1929.

• 82. Aschoff 1924.

• 83. See also Lubarsch 1921b; Penfield 1925; Rezza 1925; Jiménez de Asúa 1927. The inclusion of the microglia in this system was, however, not universally accepted, with reasons advanced including objections by Aschoff and Spatz that Hortega cells do not take up heme iron; see also Creutzfeldt & Metz 1926.

• 84. Published as Metz & Spatz 1924.

• 85. Spatz 1930a, p. 163.

• 86. del Río Hortega 1939.

• 87. del Río Hortega 1932; see also Bailey & Hiller 1924.

• 88. Held 1909; cf. also Hardesty 1904; von Fieandt 1910.

• 89. Jakob 1927a, p. 176; see also del Río Hortega 1932, pp. 486f.

• 90. Banati 2003; Kielian & Esen 2004; Rock et al. 2004; Garg et al. 2005.

• 91. See, for example, Gross 1921; Holzer 1923; Lasarew 1928.

• 92. Ribatti et al. 2006; Wiesendanger 2010.

• 93. Stern 1936, pp. 403–405.

• 94. Oberndorfer 1919; Jaffé 1920; Gross 1921; Mittasch 1921; Siegmund 1921; Scholz 1922; Metz & Spatz 1924.

• 95. Scholz 1922.

• 96. Cf. van Bogaert 1958.

• 97. Spielmeyer 1919.

• 98. Bouman 1932.

• 99. van Boeckel et al. 1923, pp. 238, 244–246.

• 100. Scholz 1922.

• 101. Scholz 1922.

• 102. Gross 1921; Klarfeld 1922. Spielmeyer (1922, p. 347), citing Gross, referred to ‘Ganglienzellgräber’, and this alternative expression was more often used by other authors.

• 103. Spielmeyer 1919; see also Oesterlin 1924; Peter 1928; Bonhoff 1948.

• 104. Glial nodules could also resemble the senile plaques of Alzheimer disease. In their pioneer description of plaques (in epilepsy; 1892) Blocq and Marinesco had, in fact, proposed that they were composed of microglia; Timmer (1925), Creutzfeldt and Metz (1926), and Globus (1928), amongst others, retained this view during the 1920s. See also the review by Critchley (1929–30), who clearly distinguished glial rosettes from senile plaques. More recently, glial nodule encephalitis has been most closely associated with CMV infection: Schmidbauer et al. 1989; Kielian 2004.

• 105. Scholz 1922.

• 106. Published as Groß 1923.

• 107. von Economo 1929a, p. 108.

• 108. Creutzfeldt & Metz 1926.

• 109. Rümke-Bakker & Bouman 1921; van Boeckel et al. 1923, p. 220.

• 110. von Monakow 1922.

• 111. Weigert 1895; see also, more recently: Kim et al. 2000.

• 112. Foix & Nicolesco 1925, p. 516. Foix and Nicolesco commented that PEP differed from PD in two features: the persistence, in some cases, of perivascular inflammation; and greater restriction of pathology to the nigra (p. 495). The PD pathology reported by the authors certainly involved more than the nigra (hardly any region of the CNS was unharmed by processes they denoted ‘precocious senility’), but their description of active inflammation in the nigra (microglial activation) is unusual for PD. As the authors did not report the source of the brain material, the possibility cannot be excluded that at least some was actually derived from PEP cases. Foix had previously compared the neuropathology of one EL (one case) with that of PD (seven cases) in Foix 1921.

• 113. Bassoe & Hassin 1919.

• 114. Spatz 1925.

• 115. Spatz 1925.

• 116. Weigert 1895.

• 117. von Fieandt 1910.

• 118. Spielmeyer 1930. Direct activation of macroglia had also been previously described. Karl Schaffer (1864–1939; Budapest) had in 1918 described different forms of glial proliferation in response to acute and chronic inflammation and nerve degeneration, as well as in response to the glia see themselves being attacked (Eigenerkrankung), as seen in progressive paralysis. These responses could combine proliferative and degenerative elements, depending upon the virulence of the pathogen, and the general state of the tissue involved: Schaffer 1918; see also Jakob 1927b; Globus 1928.

• 119. van Boeckel et al. 1923, p. 236.

• 120. Alberca Lorente 1928, p. 96; Lorente subscribed to the herpes virus hypothesis of the etiology of EL (see chapter 8).

• 121. Spielmeyer 1930.

• 122. Rößle 1923.

• 123. Cone 1928.

• 124. Alberca Lorente 1928.

• 125. Levaditi 1930. See discussion of Lhermitte’s conception of ‘neurotropic ectodermoses’ in chapter 8.

• 126. Mims 1960. It is similarly to be expected that intracerebral administration of virus during the 1920s spilled into fluid spaces, so that delivery was not as precise as assumed.

• 127. van Boeckel et al. 1923, p. 240.

• 128. Reviewed: Rock et al. 2004; Kim & de Vellis 2005; Hanisch & Kettenmann 2007; Whitton 2007; Brown & Neher 2010; Bentivoglio et al. 2011; Halliday & Stevens 2011; see Chen et al. 2010 for specific effects of Japanese encephalitis virus infection.

• 129. Stern 1928, p. 320.

• 130. Scholz 1922.

• 131. van Boeckel et al. 1923, p. 225.

• 132. ‘Mononuclear elements’ here include the protoplasmic astrocytes.

• 133. Levaditi & Harvier 1920.

• 134. Foix 1921.

• 135. Guiraud 1923.

• 136. van Boeckel et al. 1923, p. 218.

• 137. Holzer 1921.

• 138. Holzer 1926.

• 139. Elizan & Casals 1991.

• 140. Spatz 1930a, p. 247.

• 141. Achard 1921, p. 149.

• 142. von Economo 1923a.

• 143. Achard 1921, pp. 149f.

• 144. Marie & Tretiakoff 1918; Tretiakoff 1919; Levaditi & Harvier 1920; Spatz 1927, pp. 358–360.

• 145. For instance, Kohnstamm 1934.

• 146. Spatz 1930a, p. 259.

• 147. Foix & Nicolesco 1925.

• 148. This contrasted with the ‘classic’ brainstem disorder, Benedikt syndrome, characterized by CN III pareses (amongst other symptoms); in the 1920s it was also known as ‘nucleus ruber syndrome’. Overview, including history: von Halban and Infeld 1902.

• 149. During the EL period the thalamus was considered part of the basal ganglia; certain thalamic nuclei are now regarded as involved in extrapyramidal function, but not as belonging to the basal ganglia.

• 150. Achard 1921, p. 154.

• 151. Marie & Trétiakoff 1920a.

• 152. For example, Burrows 1920; Reichelt 1922.

• 153. Marie & Trétiakoff 1920a.

• 154. Luzzato & Rietti 1921.

• 155. Winther 1927, 1928; see also: Barny de Romanet 1921; Spadavecchia 1934; Dvorjetz 1935.

• 156. Such as Weimann 1925.

• 157. Klarfeld 1922.

• 158. Spatz 1925.

• 159. von Economo 1917/18; Barker et al. 1920; Calhoun 1920; Gerlach-W 1920; Guizzetti 1920; Herxheimer 1920; Siegmund 1920; Tobler 1920; Klarfeld 1920–21; Salus 1929.

• 160. Groß 1923: four of five patients; Simchowicz 1929: six of eight examined cords.

• 161. Clerc et al. 1921.

• 162. Barker et al. 1920.

• 163. Examples: Brouardel et al. 1920; Mingazzini 1921.

• 164. Rollet 1920; Salus 1929.

• 165. Burrows 1920; Calhoun 1920; Guizzetti & Giugni 1920; Hammes & McKinley 1920; Souques & Bertrand 1920; Wartenberg 1920; Weimann 1921; Bériel & Devic 1925; Péhu & Dechaume 1926, 1927.

• 166. Guizzetti 1920; Marie & Lévy 1920; Netter 1922; Verga & Uluhogian 1924.

• 167. Review: Del Bigio 2010.

• 168. von Monakow 1922.

• 169. Bassoe & Hassin 1919; Groß 1920; von Monakow 1920; Emdin 1921; Chetverikov 1925.

• 170. Calhoun 1920; Hala & Smith 1920; Bielschowsky & Henneberg 1925; Cobb 1926; Frey 1931; Agostini 1935a.

• 171. Omorokov 1925,1926.

• 172. Speransky 1926; Loeper & Forestier 1921; see also Floyd & Landon 1927.

• 173. von Economo 1917/18; Klarfeld 1922; Spatz 1930b.

• 174. For example: Monti & Tibaldi 1920; Luzzato & Rietti 1921; Smith 1924.

• 175. Baló 1924.

• 176. Tinel & Dupouy 1923.

• 177. Netter 1920, 1933; Babonneix & Hubac 1921; Da Fano 1921; Netter et al. 1921; Guillain et al. 1922.

• 178. French authors generally spoke of the ‘peduncular localization’ of lesions where German-speaking authors preferred ‘tegmentum (mesencephali)’ = ‘(Mittelhirn-)Haube’, which excludes the base of the peduncle.

• 179. Marie & Trétiakoff 1918. ‘Hyaline’ referred not to a specific substance, but to the fact that that the substance appears glassy–translucent in unstained preparations.

• 180. Marie & Trétiakoff 1918; also Marie & Trétiakoff 1920a.

• 181. Historical reviews: Sano 1910; Faull et al. 1968; Lees et al. 2008; Yudina et al. 2009; Parent & Parent 2010.

• 182. Lotmar 1926, p. 2.

• 183. Economo 1902.

• 184. Trétiakoff and Marie popularized the term ‘Lewy body’, but Spanish neurologist Lafora had employed it (‘cuerpos de Lewy’) in 1913 (the year after Lewy had summarily described them) to denote the hyaline bodies he found in PD in the oculomotor (CN III) nucleus, and to a lesser extent in those of CN VII and X.

• 185. Trétiakoff 1919, pp. 100f.

• 186. Marie & Trétiakoff 1918.

• 187. Trétiakoff 1919.

• 188. Brissaud 1895. Lotmar (1926, p. 48) noted that the patient had initially been seen by Charcot’s son, and the case published by Béchet in his 1892 thesis; a subsequent thesis (Maillard 1907) erroneously interpreted the Béchet and Marinesco–Blocq cases as separate, and Trétiakoff appears to have adopted this error. Pelnář (1913) compounded the problem by citing Brissaud’s paper as a third exemplar of the same condition. The moral of the story: one should not rely on second-hand accounts of crucial sources!

• 189. Until the 1920s the terms ‘basal ganglia’ and ‘corpus striatum’ were often but not always construed as synonyms, except by those who included the thalamus in the basal ganglia (as in the French ‘corps opto-striés’). The ‘corpus striatum’ consisted of two structurally and ontologically divergent parts: the ‘striatum’ (Vogt & Vogt 1920) or ‘neostriatum’ (Kappers 1920), that included the caudate nucleus and putamen; and the ‘pallidum’ (Vogts) or ‘paleostriatum’ (Kappers); together the pallidum und putamen constituted the ‘lenticular nucleus’. The striatum was generally seen as part of the endbrain, but Spatz (1924a) regarded it as part of the diencephalon, a thesis later explored by his student Ernst Richter (1965).

• 190. Lewy 1913, 1923.

• 191. Alzheimer 1911.

• 192. Published as Wilson 1912.

• 193. Vogt & Vogt 1918, 1919, 1920.

• 194. Spielmeyer 1920b. He continued: “They did not need to subject themselves to the deplorable habit of publishing a paper every month in order to advance their career … They did not need it, and could bide their time in quiet intellectual work until the fruits of their labor were ripe.”

• 195. Sainton 1918. Maillard himself suspected that the nucleus ruber was the mesencephalic balance centre.

• 196. Martin 1918.

• 197. For example, Lotmar 1926, p. 37.

• 198. Hohman 1925. More astounding was the fact that in 1929 Economo cited “Tetriakoff” (sic) only as one of many to ‘acknowledge’ the existence of the nigral lesion (1929a, pp. 118, 194).

• 199. McAlpine 1926a.

• 200. Published as Mingazzini 1921; Bramwell & Miller 1920; Goldstein 1921, 1922.

• 201. Levaditi & Harvier 1920; Marie & Trétiakoff 1918.

• 202. Zentralblatt für die gesamte Neurologie und Psychiatrie 30 (1923) 76f.; Medical Science. Abstracts and Reviews 7 (1923) 499 = Journal of Nervous and Mental Disease 62 (1925) 416.

• 203. Goldstein 1922.

• 204. Representative reports: Müller-Bergalonne 1919; Levaditi & Harvier 1920; Achard 1921, pp. 139–142; Foix 1921; Schaller & Oliver 1922; Fünfgeld 1923; Guiraud 1923; McKinley 1923; Hohman 1924; Jakob 1924; Omodei-Zorini 1924; Foix & Nicolesco 1925, pp. 508–516; Marinescu-Baloi 1926a; McKinley & Gowan 1926; Környey 1930; Kohnstamm 1934; see also Spatz 1922a for early overview.

• 205. Spatz 1930a, p. 258.

• 206. Hunt 1924, 1933; Lewy 1923, p. 280; Wilson 1925.

• 207. Lotmar 1926, p. 42.

• 208. Stern 1928, pp. 314f.

• 209. Stern 1936, pp. 410–414.

• 210. von Economo 1929a, p. 202.

• 211. Overview: Souques 1921.

• 212. Lhermitte & Cornil 1921.

• 213. Foix & Nicolesco 1925, pp. 537, 543.

• 214. Lotmar 1926, pp. 41–43, 98–135.

• 215. Meyers 1942.

• 216. Spatz 1930b.

• 217. Spatz 1922a.

• 218. Reviews: Müller 1922; Hernandez 1931; Koeppen 1995.

• 219. Marinesco 1909, p. 281.

• 220. Biondi 1914.

• 221. Lubarsch 1917; Odefey 1918.

• 222. Guizzetti 1915.

• 223. Spatz 1921, 1922b.

• 224. Stein 1923; Wuth 1923.

• 225. Warburg 1921.

• 226. Reviewed: Hernandez 1931.

• 227. Spatz 1922b.

• 228. Presumably added during revision of his paper; Spatz’ paper appeared in mid-1922, four weeks before Goldstein’s preliminary report at the meeting of the Gesellschaft Deutscher Nervenärzte.

• 229. Hallervorden & Spatz 1922. This paper reported the first disorder in which Spatz reported increased extrapyramidal iron levels; Hallervorden had brought a girl’s brain from Wartheburg to Munich specifically to be examined for this purpose. The investigation of this initial case of ‘Hallervorden–Spatz disease’ laid the basis for a personal and scientific friendship that endured for four decades.

• 230. Spatz 1922b.

• 231. Vogt & Vogt 1922.

• 232. Review: Sian-Hülsmann et al. 2011.

• 233. Gans 1923.

• 234. Marinesco & Draganesco 1923.

• 235. See also Spatz 1927.

• 236. Jakob 1923.

• 237. von Economo 1929a, p. 37.

• 238. von Economo 1929a, pp. 66f.

• 239. Spatz 1922a,c; Metz & Spatz 1924.

• 240. Metz 1926.

• 241. Müller 1922; Scholz 1922; Bertrand 1923; Marinesco & Draganesco 1923; Lhermitte et al. 1924a; Somogyi 1924; Uchiyama 1925; Cobb 1926; Eaves 1926; Kaneko & Aoki 1928; Kingo 1934; Yamashita 1934; see also Bodechtel 1930.

• 242. Marinesco & Draganesco 1923; Lhermitte et al. 1924a.

• 243. Lubarsch 1923.

• 244. Spatz 1922b, p. 361.

• 245. Reviewed: Hernandez 1931.

• 246. Kaneko et al. 1989; Barron 1995; Koeppen 1995.

• 247. Recent reviews: Wang et al. 2007; Crichton et al. 2011; Sian-Hülsmann et al. 2011.

• 248. Spatz 1922a, 1925, 1930b; Lucksch & Spatz 1923.

• 249. Lucksch 1925.

• 250. Goldmann 1913.

• 251. Spatz 1924b.

• 252. Goodpasture & Teague 1923a; Goodpasture 1930.

• 253. See Spatz 1933 for his later assessment of the value of dye distribution experiments.

• 254. Chetverikov 1925; Speransky 1926. For recent review of CSF anatomy and physiology: Brodbelt & Stoodley 2007.

• 255. Schükri & Spatz 1925; Seifried & Spatz 1929, 1930; Spatz 1930b; see also Seifried & Gylstorff-Sassenhoff 1958.

• 256. Schükri & Spatz 1925.

• 257. Pierre-Kahn et al. 1921; see also Schükri & Spatz 1925; Krinitzky 1926; Lowenberg 1928.

• 258. Schükri & Spatz 1925; Seifried & Spatz 1930.

• 259. Spatz 1930b.

• 260. Each virus actually travels within the nerve, but Spatz was not alone in assuming that travel via the liquid spaces was more likely, although by 1933 he was less certain.

• 261. Key & Retzius 1875.

• 262. Spatz 1925; see also Spatz 1924b, 1933.

• 263. Seifried & Spatz 1930, p. 275.

• 264. Pette 1929; Pette & Környey 1935.

• 265. Pette 1929.

• 266. Kubik & Kretz 2006, pp. 33–37.

• 267. Spielmeyer 1930.

• 268. Spatz 1930a, pp. 263f.

• 269. von Economo 1917/18, cases 4, 11.

• 270. Bassoe & Hassin 1919; see also Wartenberg 1920; Anglade 1921; Reichelt 1922; Ashizawa 1923 (cited in Kaneko & Aoki 1928).

• 271. Luzzato & Rietti 1921.

• 272. Watson 1920; Weimann 1925.

• 273. Marie & Trétiakoff 1918.

• 274. Cf. Tobler 1920.

• 275. Reviewed: Rivers 1927; Medical Research Council 1930; Baló 1935.

• 276. Kling 1926.

• 277. Goodpasture & Teague 1923b; Le Fèvre de Arric 1923; Goodpasture 1925; Stern 1926.

• 278. Crofton 1925.

• 279. Urechia 1921.

• 280. Basophilic = taking up basic dyes; acidophilic (oxyphilic, eosinophilic) = taking up acid dyes.

• 281. The stainable substance in the nucleus, consisting primarily of DNA and the basic protein structures (histones) that organize the DNA.

• 282. Da Fano 1921.

• 283. Da Fano 1924a; also Da Fano & Ingleby 1924.

• 284. Marie & Trétiakoff 1920a.

• 285. Trétiakoff 1919, p. 47.

• 286. Levaditi et al. 1921.

• 287. Da Fano 1923.

• 288. Lhermitte & Radovici 1921.

• 289. Cowdry & Nicholson 1923, 1924; see also Cowdry 1934. Intranuclear inclusions in certain viral infections, including by herpes and CMV, are termed ‘Cowdry bodies’.

• 290. Da Fano 1923.

• 291. Da Fano 1924b.

• 292. Adolf & Spiegel 1920; Volpino & Desderi 1920; Boyd 1920/21; Gamna 1921b; Weimann 1922, Cobb 1926; Redlich 1930; Donnagio 1931.

• 293. Divry 1934.

• 294. Review: Cavanagh 1999. For Buscaino’s grappoli, see Buscaino 1921, 1922.

• 295. Lhermitte et al. 1924b; Pagés et al. 1925; Cobb 1926; Greenfield 1926.

• 296. Grinker & Stevens 1929; see also Smith 1949.

• 297. Ferraro 1928.

• 298. Herzog 1921b; Meleney 1921; Lucksch 1922; with reservations: Joest 1926, Omorokow 1926; see also Dejanov 1937.

• 299. Volpino & Desderi 1920; Herzog 1921b; Guiraud 1923; Volpino & Racchiusa 1923; Dechaume 1927.

• 300. Schükri & Spatz 1925.

• 301. Guiraud 1923.

• 302. Mittasch 1921.

• 303. Volpino & Racchiusa 1922, 1923; Nishii 1929.

• 304. Somogyi 1924.

• 305. Baló 1935, p. 17; cf. Lipschütz 1921.

• 306. For instance: Lucksch 1922; Luger & Lauda 1924.

• 307. Schükri & Spatz 1925; Seifried & Spatz 1930.

• 308. Lewy 1932; cf. Covell 1932.

• 309. Dürck 1921; Buzzard 1923; McAlpine 1923; Verga & Uluhogian 1924.

• 310. Dawson 1933, 1934.

• 311. Van Bogaert 1945.

• 312. Greenfield 1950.

• 313. Greenfield 1950.

• 314. Schönberger et al. 2013. See also Bellini et al. 2005; Campbell et al., 2007.

• 315. Reviewed: Garg 2008; historical review: Katz 2009.

• 316. Stern 1928, p. 261f.

• 317. Noymer & Garenne 2000; Noymer 2008.

• 318. See overview and discussion of historical trends between 1840 and 1940: Gale 1945.

• 319. Groß 1923; see also Stern 1928, p. 262.

• 320. Meyer 1929.

• 321. Holzer 1926; Stern 1927.

• 322. Reviewed: Lotmar 1926, pp. 12f.

• 323. Cf. Weimann 1925.

• 324. Achard 1921, p. 164.

• 325. Hunt 1921.

• 326. Déjérine & Roussy 1906; see also review: Schott 1995.

• 327. Margulis 1924.

• 328. Foo & Mason 2003; Ossipov et al. 2010; Benaroch 2012.

• 329. Rollet 1920; Salus 1929.

• 330. For overview of contemporary views of the relationships between neuropathology and symptomatology in EL, and comparison of these relationships in other extrapyramidal disorders, see Lemanski 1922; Lotmar 1926.

• 331. Westphal 1877; Fischer 1878; Gélineau 1880. See also: Schenck et al. 2007 (includes English translations of Westphal and Gelineau).

• 332. Trömner 1912, pp. 76, 81.

• 333. Veronese 1910.

• 334. Gayet 1875.

• 335. See, for example, von Economo 1917/18; MacNalty 1918; Nonne 1919.

• 336. Polgár 1920.

• 337. Economo 1925.

• 338. Karplus & Kreidl 1909, 1910, 1911, 1918. Historical review: Wang 1965.

• 339. von Economo 1923b.

• 340. von Economo 1926.

• 341. For example, Goldstein 1925.

• 342. Piéron 1912.

• 343. Bard 1928; Le Gros Clark 1938.

• 344. von Economo 1926.

• 345. von Economo 1928.

• 346. Fisch 2009.

• 347. von Economo 1930, 1931a.

• 348. Demole 1927; Kleist 1929.

• 349. von Economo 1929a, pp. 68f., 218–220.

• 350. von Economo 1930.

• 351. Economo 1921.

• 352. Reviewed: Nachmansohn 1927.

• 353. Economo curiously cited Hoff and Wermer (both in Vienna, Hoff in the same clinic as Economo) indirectly, via a paper by Molitor & Pick (1926), who did not, however, cite Hoff and Wermer in this or other papers from this period.

• 354. Cf. Molitor & Pick 1926, 1929.

• 355. Pötzl 1929.

• 356. Nachmansohn 1927; Pötzl 1927; Rosenthal 1927; Spiegel 1927; Marinesco et al. 1928; Skljar 1928; Kleist 1929; Roger 1932.

• 357. Trömner 1924, 1926.

• 358. Trömner 1928.

• 359. von Economo 1929a, p. 219; von Economo 1931b, pp. 159–161.

• 360. Trömner 1931.

• 361. von Economo 1928, 1929b.

• 362. Achard 1921, p. 157.

• 363. Spiegel 1927.

• 364. Reviews: Nachmansohn 1927; Sarason et al. 1929; von Economo 1929c; Zweig 1930; Lhermitte 1931; Roger 1932. See also Kleitman 1963, pp. 341–370, especially pp. 359–362.

• 365. von Economo 1929b.

• 366. von Economo 1929b. Economo, Molitor, Pick, and Otto Pötzl published a collection of essays on various aspects of the sleep problem in 1929 as Der Schlaf, but it was popularly known as the ‘Vienna sleep book’: Sarason et al. 1929.

• 367. Lhermitte & Tournay 1927; with further papers and discussion on pages 823–887; see also Lhermitte 1931. Trömner (1928) judged the Lhermitte–Tournay paper to be good, “without, of course, surpassing the level of German knowledge”; Economo (1928) regarded it as an “excellent presentation.”

• 368. Salmon 1905, 1930.

• 369. Mingazzini 1921; Bychowski 1922.

• 370. Seletzky 1925; see also Bernhardt & Simons 1919; Rosenhain 1921.

• 371. Roger 1932, pp. 11–22.

• 372. Nachmansohn 1927.

• 373. Zweig 1930.

• 374. Pette 1923; Adler 1924; Hirsch 1924; Lucksch 1924.

• 375. Claude & Lhermitte 1917; Souques et al. 1926; Lhermitte 1927. For a pituitary tumor in a patient presenting parkinsonism: van Bogaert & Nyssen 1924.

• 376. Lucksch 1924.

• 377. Davison & Demuth 1946.

• 378. The hypothalamic suprachiasmatic nucleus would be identified as this timekeeper in the 1970s.

• 379. Trömner 1912, pp. 87f.

• 380. Gamper 1929.

• 381. Hess 1929; see also Marinesco et al. 1928.

• 382. Demole 1927.

• 383. Moruzzi & Magoun 1949; see also review by Siegel 2002.

• 384. Petsche, cited by van Bogaert & Théodoridès 1979, p. 57.

• 385. von Economo 1928.

• 386. Lucksch 1924.

• 387. Triarhou 2006.

• 388. Reviews: Fuller et al. 2006; Bentivoglio & Kristensson 2007; Stenberg 2007; Schwartz & Roth 2008; Fisch 2009.

• 389. Nauta 1946.

• 390. Moruzzi 1964.

• 391. Strümpell 1890; Leichtenstern 1892.

• 392. Oppenheim & Cassirer 1907, pp. 16–18, 87–89.

• 393. Leichtenstern 1912, p. 159.

• 394. Schmidt 1905; Kirschbaum 1920; Siegmund 1921.

• 395. Including those of Virchow & Senator 1891 and Fürbringer 1892 (same case: Koenigsdorf 1892), Bücklers 1892, and Schmidt 1892. See also review by Puin 1957.

• 396. Jorge 1920; Kuczynski & Wolff 1921.

• 397. Juhl 1921.

• 398. von Economo 1917/18, 1919a; 1929a, pp. 142–144.

• 399. von Economo 1919a.

• 400. von Economo 1929d.

• 401. Schröder & Pophal 1921.

• 402. Strümpell 1920.

• 403. Reviewed: Lafora 1920; Juhl 1921.

• 404. Siegmund 1920 (in only two cases were the cerebral hemispheres affected, a finding foreshadowed by the clinical symptoms in these cases); see also Siegmund 1921, based on 21 cases.

• 405. Baumann & de Leeuw 1933; see also Groß 1923.

• 406. Mayer 1919.

• 407. For instance, Eichhorst 1919.

• 408. Lucksch 1928.

• 409. Lucksch 1928.

• 410. Jaffé 1920.

• 411. Kuczynski & Wolff 1921.

• 412. Meerloo 1931. Similar: Bernhardt & Simons 1919.

• 413. Crome 1954.

• 414. Aronovich 1934; Stuart-Harris 1953, p. 23.

• 415. Toovey 2008.

• 416. Steininger et al. 2003.

• 417. Davison et al. 2003.

• 418. Leichtenstern 1912.

• 419. Wernicke 1881, pp. 229–242.

• 420. Gayet 1875.

• 421. Reviewed: Gutzwiller 1924.

• 422. Strümpell 1885 (see also, for instance, Gerlach-KW 1920); Häuptli 1921.

• 423. Wickman 1911, pp. 855–860; see also Oppenheim 1899a,b; Bremer 1910; Batten 1916.

• 424. See also Bozzolo 1900; Hall 1918.

• 425. Holzer 1926.

• 426. Reviews: Stern 1928, pp. 304–336; Spatz 1930a, pp. 264–266.

• 427. von Economo 1919b.

• 428. Spatz 1930a, pp. 264–266.

• 429. Greenfield 1927; possibly the case for which he included a photograph of the nigra (“20-day history”) in Greenfield 1956.

• 430. von Braunmühl 1949.

• 431. Lévy 1922, pp. 149–166.

• 432. Including d’Antona & Vegni 1922; Donaggio 1923 (1926); De Lisi 1924; Agostini 1925; De Lisi & Businco 1925.

• 433. Loss of the cytoplasmic Nissl bodies, now: rough endoplasmic reticulum, the site of protein synthesis.

• 434. For example, Marinescu-Baloi 1926a; Torvik & Meen 1966.

• 435. Goldstein 1921; Spatz 1925.

• 436. von Economo 1929a, p. 202.

• 437. Hohman 1925.

• 438. Holzer 1926.

• 439. Cf. Bodechtel & Gagel 1931.

• 440. If not always: Marchand & Pichard 1933.

• 441. Pennacchi 1930; Verga & Uluhogian 1924; Froment & Colrat 1931.

• 442. Meyer 1929.

• 443. Jakob 1923, pp. 199–215; see also Kufs 1923; Bielschowsky & Henneberg 1925; Környey 1930.

• 444. McKinley & Gowan 1926.

• 445. McAlpine 1926b.

• 446. Martin 1965; also: Martin 1967, pp. 120–124.

• 447. Lévy 1922, p. 156.

• 448. Escourolle 1972.

• 449. Marinesco 1920.

• 450. Cf. Pekelský 1922; Gagel & Bodechtel 1929.

• 451. Wimmer & Neel 1928.

• 452. Stern 1928, p. 321.

• 453. Carmichael 1931.

• 454. Greenfield 1927.

• 455. Economo 1920; 1929a, pp. 192f.

• 456. Chetverikov 1925.

• 457. Jakob 1922.

• 458. Scholz 1923; Marinescu-Baloi 1926a; Kingo 1934.

• 459. Holzer 1921, 1926.

• 460. Hohman 1925; see also Lévy 1922; Cobb 1926; Kawata 1927; Környey 1930; Frey 1931; van Bogaert 1958.

• 461. Dąbrowski 1935.

• 462. See Donaggio 1904.

• 463. Donaggio 1924; see also Donaggio 1923 (1926).

• 464. Donaggio 1924; Donaggio 1925, 1927, 1931a, 1935; see also Catalano 1930.

• 465. Delmas-Marsalet 1927. See also: Oseki 1924; Berlucchi 1931.

• 466. Lhermitte 1921.

• 467. Tamraz & Comair 2006, p. 295.

• 468. Guiraud 1928.

• 469. Buscaino 1921, 1924a,b, 1926, 1932a, 1937; Josephy 1923; Klarfeld 1923; Fünfgeld 1925; Nagasaka 1925.

• 470. For example, Scholz 1923; Zucker 1928; Giacanelli 1931; Kufs 1933.

• 471. Bodechtel & Gagel 1931.

• 472. Stern 1928, pp. 315–319; Stern 1936, pp. 415f. Contemporary review of theories of parkinsonism: Lotmar 1926, pp. 37–40.

• 473. Onuaguluchi 1964, pp. 11f.; similar in Denny-Brown 1962.

• 474. Reviewed: von Bechterew 1909, pp. 1077–1084; Riese 1924; Lotmar 1926, pp. 94f.; Spatz 1930a, pp. 273–276; Brodal 1963.

• 475. Lotmar 1926, pp. 124, 129.

• 476. Lotmar 1926, pp. 58–61.

• 477. Creutzfeldt 1924; similar in Marinescu-Baloi 1926a.

• 478. Spatz 1930a, p. 275.

• 479. McAlpine 1926a, citing Hassin & Bassoe 1926. Dutch pathologist Anton Petrus Timmer (1940) presented evidence of age-related nigral atrophy that cases of PD in which the nigra was largely unscathed.

• 480. Jakob 1923, p. 382.

• 481. Spatz 1931.

• 482. See, for instance, Hunt 1933; Alexander 1942; Benda & Cobb 1942; Heath 1947.

• 483. Stern 1928, p. 375.

• 484. Pette 1942, p. 206. See also Birkmayer 1965, pp. 163–170; and this book, pp. 322ff.

• 485. Hassler 1937, 1938, 1939.

• 486. Defined by Jacobsohn 1909; see also Foix & Nicolesco 1925, p. 520.

• 487. Beheim-Schwarzbach 1952.

• 488. Spatz later (1950) wrote to Vogt that he had accepted the post only after Vogt’s request that he do so (Peiffer 2004, pp. 631f.). In 1948 he had commented that he had accepted the “pernicious inheritance” only with heavy heart, and on the advice of Max Planck (letter to Eugen Fischer: ibid., p. 609).

• 489. Klaue 1940.

• 490. Spatz, as preface to Klaue 1940.

• 491. Foley 2003, pp. 437–462.

• 492. Greenfield & Bosanquet 1953.

• 493. Published as Earle 1966.

• 494. Reviews: Muskens 1927; Marinesco & Draganesco 1932; Spadavecchia 1934; Cardona 1936; Rubins 1943.

• 495. Falkiewicz & Rothfeld 1925; Popowa 1925; Scharfetter 1925; Wimmer 1926; see also Matiar 1955.

• 496. Margulis & Model 1926.

• 497. Muskens 1927; see also Marinesco & Nicolesco 1937.

• 498. Lotmar 1926, p. 26; Flach & Palisa 1936.

• 499. Meyer 1929; Buscaino 1932b.

• 500. Lafora 1913; Hallervorden 1933.

• 501. Greenfield & Matthews 1954.

• 502. Review: Remmers 2005.

• 503. Cf. Karplus & Kreidl 1909, 1910, 1911, 1918; Müller 1920, 1931; Brugsch & Lewy 1926–1931.

• 504. Lotmar 1926, pp. 67f.

• 505. Marie & Trétiakoff 1920b; see, for example, Guizzetti 1930, 1932; D’Antona 1931.

• 506. Fendel 1921.

• 507. Howe 1921.

• 508. De Costobadie 1924.

• 509. Schinck 1924; Orzechowski & Mitkus 1925; van Bogaert 1928.

• 510. Eaves & Croll 1930.

• 511. Eaves & Croll 1930.

• 512. Parhon et al. 1924; Parhon & Stefanesco-Dragomireano 1935; see also Lotmar 1926, pp. 67–72; Stertz 1931.

• 513. Howe 1921.

• 514. Wilckens 1925.

• 515. Holzer 1926.

• 516. Meyer 1927.

• 517. Bodechtel & Gagel 1931.

• 518. Scholz 1923.

• 519. Jakob 1923.

• 520. Mackenzie 1927.

• 521. Környey 1930; Hohman 1925. See also the shift from lipophilic to lipophobic nerve cell typus described by Obersteiner 1903.

• 522. Schaffer 1924/25, 1931; Környey 1930.

• 523. Foix & Nicolesco 1925, pp. 340f.

• 524. Gowers 1902; Edinger 1908.

• 525. Pette 1925.

• 526. Pette 1925, 1929.

• 527. Pette 1931; Pette & Környey 1935.

• 528. Lucksch & Spatz 1923; see also Spatz 1925.

• 529. Spatz 1930b.

• 530. Spatz 1930b,c.

• 531. Noguchi & Moore 1913.

• 532. Spatz 1930b,c.

• 533. Cf. Guizzetti 1920.

• 534. Carmichael 1931.

• 535. Stern 1936, pp. 441f.

• 536. Steiner 1929.

• 537. Stern 1936, pp. 442–445.

• 538. Hoff et al. 1929; Pette 1929; Spielmeyer 1930; also Steiner 1929.

• 539. von Economo 1929a, pp. 156–159, 190–193.

• 540. Stern 1936, p. 412.

• 541. For example, Messing 1935.

• 542. Stern 1936, p. 444.

• 543. van Bogaert 1958.

• 544. Reviewed: Whitton 2007; Lee et al. 2009; Tansey & Goldberg 2010; Ferrari & Tarelli 2011; Halliday & Stevens 2011.

• 545. Contemporary overviews: Schade 1923; Růžička 1924 (and further articles in the same journal issue); Kraus 1926; Bechhold 1929; Seifriz 1936; Staudinger 1940; Lepeschkin 1949.

• 546. von Braunmühl 1932, 1934.

• 547. Review: Hantz 2006, pp. 21–30.

• 548. Hallervorden & Spatz 1932–33; cf. also Khonsari & Calvez 2007.

• 549. Peiffer 2004, pp. 32–34, and cited correspondence.

• 550. Peiffer 2004, p. 917.

• 551. Peiffer 2004, p. 918.

• 552. Hallervorden 1933.

• 553. Hallervorden 1933, 1934a.

• 554. It is now known that both Alzheimer neurofibrillary tangles and Pick bodies are composed of tau (τ) protein.

• 555. Hallervorden 1934a,b, 1935; cf. Greenfield & Bosanquet 1953; Rövéti 1956.

• 556. Hallervorden 1933.

• 557. Hallervorden 1933, 1934a,b, 1935.

• 558. Fényes 1932.

• 559. Peiffer 2004, p. 918.

• 560. Pette 1942.

• 561. van Bogaert 1958, pp. 338f.

• 562. Hallervorden 1935; cf. also Pette 1942, pp. 172f.

• 563. Borremans & van Bogaert 1935.

• 564. v. Braunmühl 1934. In 1957(a), Hallervorden wrote in an obituary that Braunmühl’s once somewhat unusual concepts of neurocellular physiology had, in the meantime, been integrated into orthodox models of nervous function; this comment was, however, recorded as a side interest in comparison with his services to shock therapy and leucotomy.

• 565. Scholz 1957a,b.

• 566. von Braunmühl 1949; see also von Braunmühl 1957.

• 567. Hallervorden 1957b.

• 568. Greenfield 1955.

• 569. Hechst 1934.

• 570. Yamashita 1934.

• 571. Borremans & van Bogaert 1935; Divry & Evrard 1937.

• 572. Roncati 1939.

• 573. Reviewed: Grünthal 1930; Fényes 1932.

• 574. Beheim-Schwarzbach 1952, citing Godlowski 1931. Lewy (1923, pp. 261–264) had also described Alzheimer fibrillary changes in the nucleus basalis.

• 575. von Buttlar-Brentano 1955.

• 576. Greenfield & Bosanquet 1953.

• 577. Marie & Trétiakoff 1918.

• 578. Greenfield & Bosanquet 1953.

• 579. Grütter 1921.

• 580. Rostan 1928; Donaggio 1931b.

• 581. Foix & Nicolesco 1925, p. 514.

• 582. Bertrand & Chorobski 1929.

• 583. Klarfeld 1922; Marinescu-Baloi 1926a,b; Hallervorden 1934b.

• 584. Alberca Lorente 1928.

• 585. Stern 1936, pp. 414, 422; Rietti 1935, p. 68.

• 586. Other reports: Tatetsu 1958; Hirano & Zimmermann 1962; Torvik & Meen 1966; Ishii 1968; Wiśniewski et al. 1970; Miyasaki & Fujita 1977; see also Forno & Alvord 1971; Escourolle 1972.

• 587. Greenfield 1956.

• 588. Wiśniewski et al. 1970.

• 589. Bernheimer et al. 1973.

• 590. Haraguchi et al. 2000.

• 591. Hof et al. 1992; Buée-Scherrer et al. 1997.

• 592. Jellinger 2009; in all but one of the eight cases, the patients had died at 65 years or later; one had been diagnosed with Alzheimer disease. See also Josephs et al. 2002.

• 593. For example: Klaue 1940.

• 594. 6 March 1933: Peiffer 2004, p. 484.

• 595. Hirano & Zimmermann 1962.

• 596. Geddes et al. 1993.

• 597. von Braunmühl 1949.

• 598. Torvik & Meen 1966, citing Den Hartog Jager & Bethlem 1960; Bethlem & Den Hartog Jager 1960.

• 599. Geddes et al. 1993.

• 600. Elizan et al. (1989) found no tangles in archival tissue from 1920 (acute EL), nor in tissue from the later ‘EL’ patient described by Rail et al. in 1981 (see p. 802).

• 601. Forno & Alvord 1971.

• 602. For example, Ishii & Nakamura 1981.

• 603. Gibb et al. 1989.

• 604. Review: Williams 2006.

• 605. Geddes et al. 1993; Pramstaller et al. 1996.

• 606. Review: Steele 2005.

• 607. Symptoms associated with PSP (vertical supranuclear gaze palsy, eyelid apraxia) were reported in the later courses of six cases of chronic EL, but this was unusual: Wenning et al. 1997.

• 608. Caparros-Lefebvre et al. 1998; post mortem examination of the same woman: Deramecourt et al. 2011.

• 609. Berger 1931, 1933.

• 610. Jasper 1936. Jasper does not appear to have published these findings in detail.

• 611. Gibbs & Gibbs 1947; also Hubach 1959.

• 612. Sigwald & Piot 1953.

• 613. Levin 1948.

• 614. Schwab & Cobb 1939; England et al. 1959.

• 615. Onuaguluchi 1964, pp. 82–93.

• 616. Sacks 1991, pp. 327–332.

• 617. Howard & Lees 1987.

• 618. Fleury et al. 1966.

• 619. Thiébaut et al. 1967.

• 620. Meyers et al. 1949.

• 621. Fuchs 1921; Pollak 1921.

• 622. Leyser 1923; Markovits 1934; later review: Keup 1954.

• 623. Guiraud 1928.

• 624. Stern 1936, pp. 419f.

• 625. De Lisi 1924; Rizzo 1924; Agostini 1925; Graziani 1925, 1926; see also Smith 1924; De Giacomo 1931; Matsumura 1933.

• 626. Bolsi 1925.

• 627. Baló 1924.

• 628. 200 mL milk on an empty stomach elicits ‘digestive leukocytosis’ in those with a healthy liver, leukopenia in those with liver disease; from the mid-1920s quinine was often used in place of milk.

• 629. Stern & Meyer-Bisch 1922; Ottonello 1924; Runge & Hagemann 1924; Pedrinoni 1925; von Fejér & Hetényi 1927; Outeirino et al. 1931; Cristini 1932; Marthinsen 1932; Macchia & Colucci 1938. For Widal test in EL: Küppers 1938.

• 630. Xavier 1923; O'Flynn & Critchley 1925; Schoenemann 1926; von Joó 1931.

• 631. Schargorodsky & Scheimann 1927a,b, 1928.

• 632. Caramazza 1937; Gabrici 1941.

• 633. Hess & Goldstein 1926, 1932; Tkatschew & Axenow 1926; Dresel & Lewy 1922.

• 634. Sweet et al. 1941.

• 635. Heilbrunn et al. 1945.

• 636. van Bogaert 1958.

• 637. Burkhard et al. 2003.

• 638. Cf. Noone et al. 2008; Ferrara & Jankovic 2009; Fernández-Rodriguez et al. 2010; Kim et al. 2010; see also Alarcón & Giménez-Roldán 2005; Butterworth 2007.

• 639. De Lisi & Businco 1925; see also Baló 1924; De Lisi 1924.

• 640. Carlsson 1959; Sano et al. 1959, 1960.

• 641. Ehringer & Hornykiewicz 1960; Sano 1960, 2000.

• 642. Reviewed: Foley 2000; 2003, pp. 409–416.

• 643. Bernheimer et al. 1965.

• 644. Eight patients had suffered acute EL between 1920 and 1926, and one each in 1935 and 1942; two patients included no definite acute phase in their history. PEP commenced between the ages of 2 and 68 years, with an interval between acute and chronic EL of 2 to 30 years. The age at death lay between 43 and 78 years.

• 645. Bernheimer et al. 1973.

• 646. Lewy 1923, pp. 39, 336, 625.

• 647. Környey 1930.

• 648. Reviews: Block et al. 2007; Hanisch & Kettenmann 2007; Long-Smith et al. 2009; Sugama et al. 2009; Brown & Neher 2010; Halliday & Stevens 2011.

• 649. Stern 1936, p. 375; see also Greenfield 1927; Spatz 1930a, pp. 264–266.

• 650. HIV is a retrovirus, and persists by incorporating its genetic material into that of its host cells, including microglia.

• 651. Reviewed: Maehle 2009.

• 652. Nathanson 2008.