269 Brainstem, cerebellar and limbic in autism Eric Courchesne Recent autopsy and/or quantitative magnetic resonance imaging studies of autistic patients have identified agenesis of the superior olive, dysgenesis of the facial nucleus, reduced numbers of Purkinje neurons, hypoplasia of the brainstem and posterior cerebellum, and increased neuron-packing density of the medial, cortical and central nuclei of the amygdala and the medial septum. As neurogenesis occurs for these different neuron types during approximately the fifth week of gestation, the possibility is raised that this may be a ‘window of vulnerability’ for autism; the likely etiologic heterogeneity of autism suggests that other windows of vulnerability are also possible. Addresses Department of Neurosciences, School of Medicine, University of California, San Diego, California 92093, USA and Laboratory for Research on the Neuroscience of Autism, Children’s Hospital Research Center, 6110 La Jolla Shores Drive, Room 200, La Jolla, California 92037, USA; e-mail: ecourchesne@ucsd.edu Current Opinion in Neurobiology 1997, 7:269-278 Electronic identifier: 0959-4388-007-00269 0 Current Biology Ltd ISSN 0959-4368 Abbreviations fMRl functional MR imaging 10 intelligence quotient MR magnetic resonance Table 1 neuroanatomical abnormalities Introduction Historically, infantile autism has been nearly impervious to attempts at uncovering the neuroanatomical abnormalities that underlie its characteristic neurobehavioral deficits. Because it involves developmental abnormalities of motor, sensory, and cognitive functions, attention, speech, lan- guage, affect and social communication, a correspondingly large number of different neuroanatomical systems have been speculated to be maldeveloped. New autopsy and structural magnetic resonance (MR) imaging evidence point to several specific sites of apparently very early maldevelopment. This review focusses on the potential structural and functional sequelae of this early anatomical maldevelopment. Autopsy studies Since 1980, only seventeen autopsy cases of autism have been reported in abstracts, brief reports and chapters (see below and Table l), and these have been compared to fewer than a dozen control cases. Analyses have included neuron counts, subjective assessment of conventionally fixed tissue, and brain weight, but have not included neuroimmunohistochemical analysis. Brainstem, limbic and cerebellar abnormalities in autism: autopsy and MR imaging evidence. Brainstem abnormalities Limbic abnormalities Cerebeilar abnormalities Autopsy evidence Rodier et al. 1996 [4**] MR imaging evidence Gaffney et a/. 1988 [18] Hashimoto et a/. 1995 [17**] Autopsy evidence Bauman and Kemper 1985 [40] Bauman and Kemper 1994 [l] Raymond et al. 1996 [8’1 MR imaging evidence None Autopsy evidence Williams et a/. 1980 [2] Bauman and Kemper 1985 1401 Ritvo et al. 1986 1131 Bauman and Kemper 1986’ Bauman and Kemper 19907 Arin eta/. 1991t Fehlow et a/. 1993 [14] Bauman and Kemper 1994 111 MR imaging evidence Courchesne et a/. 1987 1201 Gaffney et a/. 1987 [21] Courchesne et a/. 1988 [23] Murakami et a/. 1989 [22] Ciesielski et a/. 1990 [29] Riven et al. 1992 [261 Kleiman et a/. 1992 1241 Courchesne et a/. 1994 125,271 Saitoh et a/. 1995 [l Q**l Zilbovicius et a/. 19959 Hashimoto et al. 1995 [17*] *ML Bauman, TL Kemper, abstract, Neurology 1986. 36:lQO. ML Bauman, TL Kemper, abstract, Neurology 1990, 40~359. SDM kin, ML Bauman, TL Kemper, abstract, Neurology 1991, 41:307. 5M Zilbovicius et al., abstract, Neurology 1995, 45:A162.