the autism myth of in-utero timing

THE AUTISM MYTH OF IN-UTERO TIMING a commentary on the autism-timing speculations of Bauman and Kemper

by Teresa Binstock Researcher in Developmental and Behavioral Neuroanatomy My writings do not constitute medical advice. Instead, they represent a seeking to understand autism-spectrum disorders and their causes and associated traits. This monograph was originally posted to the autism-list of St. Johns University.

>>> Posting number 13493,
dated 11 May 1997 20:11:30

.....PRELUDE.....
The following paper is a pre-publication draft of an article to be submitted and is
here presented so as to induce comments leading to an improved final draft. This
document (if and only if in its entirety) may be shared with other persons and may
be cited as follows:

Binstock T. Changing the autism paradigm: a critique of Kemper &
Bauman's speculations regarding in-utero timing. Bit.listserv.autism,
May 5 1997.

.....ABSTRACT.....
Because the findings and speculations by Bauman and Kemper (B/K) are often cited in
autism articles and have shaped the way people think about autism, a critique of
those findings and speculations is warranted, especially given that (i) the B/K
findings are not in full accord with findings from other researchers, (ii) the B/K
speculations about in-utero timings are based upon knife-lesions in an animal model
not necessarily applicable to humans, (iii) the B/K invocation of non-gliosis as
necessarily indicating in-utero timing is contrary to recent findings about neuronal
remodeling subsequent to excitotoxic lesions, and (iv) the B/K inferior olive,
cerebellum rationale (a) derives primarily from a 1908 study in which cerebellar
lesions were the result of extreme pathologies not seen in autism, and (b) is
contrary to recent findings indicating lack of gliosis in target-deprived neuronal
alterations in adult animals.
In this critique, three conclusions are offered: (i) Not all autistics have
cerebellar features identical to those described by Bauman and Kemper; thus the B/K
findings represent a subset of autistics and do not represent all cases of autism;
in fact, B/K's stringent criteria for selection and exclusion of autopsy patients
may have induced a selection bias affecting observations derived from their
findings. (ii) Contrary to B/K speculations, neither lack of gliosis nor lack of
retrograde cell loss in the inferior olivary nucleus necessarily implies in-utero
timing of altered cerebellar morphology. (iii) Not all autisms are in-utero with
regard to timing of causality.

I.....INTRODUCTION.....

The work and writings of Bauman and Kemper are important to the understanding of
autism; and two aspects are here considered: (i) actual findings, and (ii) B/K
speculations about the meaning of those findings. Definitions of terms such as
gliosis, glial fibrillary acidic protein, apoptosis and necrosis are included prior
to the citations.

A. Bauman & Kemper findings:
1. B/K's temporal lobe findings (1,9, 9b) are similar to affected locales
described by other researchers -- eg, the recent MRI studies of persons autistic
with temporal lobe tuberous sclerosis (9c). Furthermore, traits associated with
temporal lobe regions atypical in autism are consistent with data from
neurophysiological studies in humans and other primates -- eg, eye-contact avoidance
and the amygdala; memory and the hippocampus (reviewed in 9d, 9e).
2. With regard to size, B/K's cerebellar findings are not consistent with
findings of other researchers (3-6); as a result, cerebellar findings in autism have
been described as "controversial" (9f).
3. B/K report no gliosis and no gliosis-related scarring in the cerebellum
(reviewed in 9).
4. B/K findings include descriptions of neurons within the inferior olivary
nucleus: "In all brains [among B/K's highly selected subset of autistics], the
inferior olivary nucleus failed to show retrograde neuronal loss. Instead, in the
younger individuals, the neurons that project to the [cerebellar] areas of decreased
number of Purkinje cells were unusually large and in the older brains unusually
small..." (1).

B. Bauman & Kemper speculations:
1. B/K use their cerebellar/gliosis findings as the basis of a rationale
whereby all autisms occur in utero, arguing that "The absence of the glial cell
hyperplasia suggests that the [cerebellar] lesions have been acquired early in
development." [meaning in-utero; see ref 9]
2. B/K use their inferior olivary nucleus findings similarly, ie, in support
of a speculation that all autisms occur in utero, and state, "in the absence of the
obligatory retrograde cell loss in the olive, it is likely that the cerebellar
cortical lesions seen in autism have their onset at or before this time..." ie,
after or before "30 to 32 weeks of gestation" (9, 9a).

II.....CLARIFICATION AND CRITIQUE OF BAUMAN & KEMPER FINDINGS.....

Not all autism autopsy findings are in accord with the findings reported in Bauman
& Kemper (1). In a 1980 paper describing autopsies of four individuals with autism
(2), only one was described as having reduced density of cerebellar Purkinje cells;
and when autistic patients representative of the autistic spectrum are studied by
neuroimaging, much size variation is described for various parts of the cerebellum
(eg, 3-6).
Similarly, since the cerebellum is central to many aspects of motor
coordination (7), lack of cerebellar involvement in late-onset autisms is suggested
in a passage by Isabelle Rapin, "At least 40 percent of parents report that their
infant or toddler... experienced a regression, usually insidious, but occasionally
abrupt, in language, sociability, and play... The regression is rarely if ever
associated with a regression in motor skills..." (8). In other words, while
manifesting features with temporal lobe substrates, late-onset autisms in persons
having no decrease in coordination may have minimal or even total lack of cerebellar
involvement. Here is an example of possible selection bias; to the best of my belief
and knowledge, no autopsy study of individuals with autism has focused upon
individuals with or without major difficulties in physical coordination.

III...... CLARIFICATION AND CRITIQUE OF BAUMAN & KEMPER SPECULATIONS:

A. How relevant are certain of the B/K citations regarding gliosis, lack of gliosis,
and in-utero timing?
Based upon a perceived lack of gliosis and of gliosis-related scarring in
cerebella of their autopsied patients, Bauman and Kemper speculate that lack of
gliosis and scarring in their stringently selected subgroup of autistics implies
in-utero timing for causal events in autism (1). In summarizing the B/K findings
(9), Bauman cites a 1940 article (10) and writes, "The absence of the glial cell
hyperplasia suggests that the lesions have been acquired early in development.
Brodal... has noted that, in animal studies, there is a progressively decreasing
glial response following cerebellar lesions at increasingly early ages."
However, in adult animals, various kinds of neuronal lesions induce a range of
effects, and gliosis is *not always present* in a surviving animal, especially as
the time-period increases subsequent to the lesion (11). This is an extremely
important point and appears to stand in direct contrast to the B/K rationale whereby
lack of gliosis and gliosis-related scarring are presumed necessarily to imply "in
utero timing".
In offering inferior olive/cerebellum relationships as further indication of
in-utero timing for autism (9), Bauman also cites Holmes and Stewart; yet their
findings are not directly parallel to autism, because "Our investigations have been
limited to the examination of the olives in cases in which there had been
destructive lesions of various portions of the cortex of the cerebellum." (12).
Importantly, none of the cerebella in the eight cases described by Holmes and
Stewart is even close to the kind of altered cerebellar structure described by
Bauman and Kemper (1); furthermore, none of the eight cases was induced by an
etiology or pathogenesis known to occur in autism.
The discrepancy between the Holmes and Stewart cerebella and the cerebella from
the autopsy-subgroup of autistics analyzed by Bauman and Kemper (1, 12) raises
doubts about the validity of B/K's inferior- olive/cerebellum rationale (stated in
9a) as necessarily applicable in autism -- a point further addressed below. In other
words, a model wherein all autisms are presumed to occur in-utero is *not*
necessarily valid and has *not* been established by the Bauman Kemper findings nor
by their speculations about those findings.

B. The lack of gliosis and scarring described by Bauman and Kemper is very important
in their speculations asserting in-utero timing for the causes of autism; however,
new data suggests an alternative significance for lack of gliosis & scarring
reported by Bauman and Kemper:
1. Although cited in Bauman's review (9), Brodal's article was
based upon knife lesions in sub-primate animals (10). His
article's rationale may not be applicable in most cases of
autism, ie, for persons in whom the causal processes were different
from knife-induced cuts of the cerebellum.
2. Different kinds of neuronal lesions induce differing kinds
of cell death, ranging from necrosis to apoptosis (11, 13-14);
knife-induced lesions generate necrosis and are different from
physiological, excitotoxic lesions that oftentimes can induce
apoptosis without necrosis.
3. Sub-necrotic apoptosis, for instance as induced by
excitotoxins, does not always leave residual scarring (11, 14,
15); and some cases in which gliosis is *temporary* are caused
by excitotoxins with human applicability, such as kainate (a
glutamate analog) and bilirubin (15).
4. Reductions of neuronal densities can occur subsequent to
birth, even in animals (25-26).
5. Many cases of autism are manifested postnatally, sometimes
subsequent to years of normal development; and some such
autisms are reversible (27-29).

>>> Posting number 13494, dated 11 May 1997 20:16:39
2 Changing the autism paradigm re: timing, part 2 of 4

C. Kemper and Bauman have asserted, via an inferior olivary nucleus rationale, that
autism's cerebellar alterations necessarily occur in utero. This assertion is
actually a speculation, has been taken as virtual gospel by many researchers, MDs,
and parents, and seems to be erroneous. But let us read some of the original
rhetoric:
"The cerebellar changes provide the best insight into timing
of the pathologic process. The absence of retrograde loss of
inferior olivary neurons is a striking finding in these
brains. The neurons in the inferior olive topographically show
neuronal loss following cerebellar lesions from birth
on...[citing 10, 12], indicating a tight interrelationship
between these two cell populations. In normal human
development, this relationship is established after 30 weeks
gestation... The absence of retrograde cell loss in the
inferior olive of the autistic brains therefore suggests that
the decreased number of Purkinje cells was present before this
time." (1). However:

1. The knife cuts described by Brodal and the severe cerebellar pathologies
described by Holmes (10, 12) are induced in ways profoundly different from causes
of cerebellar findings in autism; and different kinds of lesions induce different
kinds and timings of gliosis, some of which is not permanent -- eg, when induced by
excitotoxins such as kainate or bilirubin (15). Consider a 1994 quote from
O'Callaghan:
"On the basis of extensive reports in the literature of
trauma-induced glial scarring of the CNS..., one of our
initial assumptions was that toxicant-induced reactive gliosis
would also be a permanent condition. All of our results
suggest that, in general, chemical-induced injury of the CNS
results in a time-dependent, not a permanent gliosis, based on
assays of GFAP." (15).
With possible significance to autism, (i) intraventricular kainate induces
excitotoxic effects "in the Purkinje layer of the cerebellar cortex" (30), and
excesses of uncongugated bilirubin are known to have an affinity for cerebellar
Purkinje cells (15, 31) and can induce traits akin to reports from some parents of
autistic children (32-35):
"The characteristic signs of kernicterus in the newborn are
lethargy and weakness of suckling, followed by seizures,
opisthotonos, choreoathetosis, spasticity and high-pitched
cry, and sometimes gastric or pulmonary bleeding tendency..."
(35).

2. In exploring cerebellum links with the inferior olivary nuclei, we can turn to
recent studies that have focused upon the loss of target neurons and the
preservation or non-preservation of afferent neurons. These studies indicate that
altered neuronal structure can occur in adult neurons; in other words, structural
changes in neurons linking two nuclei can occur in adult animals and therefore is
not necessarily an event occurring only in utero. Consider some comments from a 1995
study by Marty and Peschanski (36), who used excitatory lesions of the adult
thalamus so as to explore morphological changes in afferent neurons from dorsal
column nuclei:
a. "In neuron-specific...sections, a 20% decrease in the
mean longest diameter...was detected at 4 months postlesion."
b. "This somatic atrophy was accompanied by a loss of distal
dendritic arborizations..."
c. "...staining did not reveal detectable alterations of the
metabolic activity of these neurons, and an ultrastructural
study also failed to demonstrate major changes in the neuronal
somata."
d. "Cell counts indicated a much delayed death of 25% of the
neurons at 10 months postlesion, whereas no neuronal death was
detected at seven months."
e. "The glial cells appeared unaltered...when using OX-42
antibodies or antiglial fibrillary acidic protein...
antibodies."
f. "These results suggest that the hypothesis of a necessary
continuous support by target cells does not hold as firmly for
the adult central nervous system as during development."

3. That "glial cells appeared unaltered" suggests that gliosis and related scarring
were not evident. That the process of excitotoxic neural death was very slow
suggests that non-necrotic apoptosis without gliosis (14) may have been the
mechanism by which the neurons died -- a process with parallels in humans, given the
roles of excitotoxins such as glutamate and unconjugated bilirubin (15-17) and
given, in humans, the reduced expression of anti-apoptotic protein bcl-2 in
cerebellar Purkinje cells and in CA1, CA2, and CA3 regions of the hippocampi (18).
Enhanced levels of excitotoxins are also (i) associated with hypoxia, febrile
seizures, and status epilepticus (19-20) and (ii) are enhanced by slight increases
in febrile temperatures (21). Furthermore, some such events might occur unnoticed
by parents or physicians because (i) non-convulsive status epilepticus occurs and
is not always recognized (22-23), and (ii) status epilepticus and other seizures can
occur during sleep (24) and do so in ways that affect behavioral traits, cognitive
performance, and language (24a).

4. The findings regarding target-induced cellular changes (36) imply that "The
absence of retrograde cell loss in the inferior olive of autistic brains" (1) is
*indeterminate* regarding the pathogenic timing of cerebellar atypicality in autism,
even with regard to the B/K autopsy patients. In other words, the findings of Kemper
and Bauman (1) do not necessarily imply "in utero timing" as the only possible time
period during which cerebellar atypicalities can occur in autism.
Such neuronal changes could be acquired postnatally in humans -- a possibility
quite consistent with numerous cases of autism described as preceeded by a long
period of normal development (32-34); and, given the role of the cerebellum in motor
gestures (8), the possibility remains that autistic individuals with no motor
problems may have no significant pathology of cerebellar structures.

*****

IV.....CONCLUSIONS.....
This critique offers three conclusions:
1. PET-scans, MRI, and case histories suggest that not all
autistics have cerebellar features identical to those
described by Bauman and Kemper.
2. Lack of gliosis/scarring does not necessarily imply in-
utero timing of altered cerebellar morphology.
3. Not all autisms are in-utero with regard to timing of
causality.

In review: although central to the B/K rationale (1), knife-cuts and cerebellar
pathologies like tumors (10,12) are not similar to what occurs in most cases of
autism. In the absence of such severe neuronal injuries, gliosis and related
scarring are not necessarily permanent (11, 14-15). Disconnections between formerly
connected nuclei can occur subsequent to birth and can do so with altered cell
morphology yet without lasting indications of gliosis (36).

For these reasons, I believe (i) although the rhetoric in their articles conveys
otherwise, the Bauman & Kemper findings regarding cerebellar morphology are
applicable in some but not in all cases of autism, and (ii) Bauman & Kemper's
speculations that all cases of autism occur in utero are contrary to fact and may
not even have been the sequence for the patients autopsied by Bauman and Kemper (1).
Most importantly, etiological and pathogenic events as causes of autism are not
limited to in-utero timings.

>>> Posting number 13495, dated 11 May 1997 20:19:51
3 Changing the autism paradigm re: timing
>>> Posting number 13496, dated 11 May 1997 20:24:26
4 Changing the autism paradigm re: timing

.....DEFINITIONS.....

Apoptosis: occasionally called "programmed cell death", apoptosis refers to a
process by which cells -- eg, neurons -- can die and disintegrate as a result of
signals and proteins generated internal to the cell. In some circumstances,
apoptotic processes can be initiated in response to signals external to the cell.
Apoptosis is different from necrosis.

Excitotoxic: in many neurons, excitatory processes can be toxic, especially if too
prolonged and/or too severe.

GFAP, Glial fibrillary acidic protein: "the protein forming the glial filaments of
the astrocytes... an immunhistochemical marker of these cells..." (Dorland's 28th).

Gliosis: "an excess of astroglia in damaged areas of the central nervous system"
(Dorland's 28th).

Necrosis: "the sum of the morphological changes indicative of cell death and caused
by the progressive degradative action of enzymes..."
(Dorland's 28th).

Sub-necrotic apoptosis: a process of neuronal death that is slow and that produces
fewer, if any, lasting signs (see refs 11-12, 14).

.....REFERENCES.....

1. Kemper TL, Bauman ML. The contribution of neuropathologic studies to the
understanding of autism. Neurologic Clinics 11.175-197 1993.
2. Williams RS, Hauser SL, Purpura DP, DeLong R, Swisher CN. Autism and mental
retardation: neuropathologic studies performed in four retarded persons with
autistic behavior. Arch Neurol 37.749-53 1980.
[case histories presented in some detail]
3. Courchesne E, Townsend J, Saitoh O. The brain in infantile autism: posterior
fossa structures are abnormal. Neurol 44.214-23 1994.
4. Kleiman MD, Neff S, Rosman NP. The brain in infantile autism: are posterior fossa
structures abnormal? Neurol 42.753-60 1992.
5. Saito O, Courchesne E, Egaas B, Lincoln AJ, Schreibman L. Cross- sectional area
of the posterior hippocampus in autistic patients with cerebellar and corpus
callosum abnormalities. Neurol 45.317-24 1995.

6. Shifter T, Hoffman JM, Hatten HP, Hanbson MW, Coleman RE, DeLong GR.
Neuroimaging in infantile autism. J Child Neurol 9.155-61 1994.
[This article presents substanial information about each of 13
patients; 10 of 13 had seizure disorder; patient #11 was late
onset and showed little if any findable indications via PET or
MRI; autistic patients with infectious etiologies were
excluded.] ** "Although neuropathologic studies have
demonstrated cellular abnormalities in the cerebellum and
cerebellar vermis hypoplasia..., only one of our patients had
a metabolic or anatomic abnormality in the cerebellum."

7. Ghez C. The cerebellum. Chapter 41 in: Principles of Neural Science, 3rd ed;
Kandel ER, Schwartz JH, Jessell TM, editors; Appleton & Lange, Norwalk 1991.
8. Rapin I. Introduction and overview. Chapter 1 in: The Neurobiology of Autism.
Bauman ML, Kemper TL, editors. The Johns Hopkins University Press, Baltimore 1994.
9. Bauman ML. Microscopic neuroanatomic abnormalities in autism. Pediatrics 87.791-6
1991.

9a. Rationale regarding inferior olivary nucleus (from cite 9):
"...the preservation of neurons in the principal inferior
olive further supports an early origin for the cerebellar
lesions [seen in B/K's highly selected subgroup of autistics].
Retrograde loss of olivary neurons regularly occurs following
cerebellar lesions in immature postnatal and adult animals...
and in neonatal... and adult humans..., presumably because of
the close relationship of the olivary climbing fiber axons to
the Purkinje cell dendrites... In the fetal monkey, it has
been shown that prior to establishing their definitive
relationship to the Purkinje cell dendrites, the olivary
climbing fibers synapse in a transitory zone beneath the
Purkinje cells called the lamina dissecans... In the human
fetus, this transient zone is no longer evident after 30 to 32
weeks of gestation... Therefore, in the absence of the
obligatory retrograde cell loss in the olive, it is likely
that the cerebellar cortical lesions seen in autism have their
onset at or before this time."
[I believe that this rationale may be erroneous. (i)
Bauman utilizes cites wherein the cerebellar lesions
were extremely unlike cerebellar atypicalities seen
in some cases of autism; (ii) A better parallel can
be found in adult neuronal deteriorations subsequent
to alterations in target neuronal populations as a
result of apoptosis-inducing excitotoxic lesions
(see reference 36); and (iii) Although retrograde
cell loss occurred in human and animals with severe,
non-autistic-like cerebellar lesions (as cited by
Bauman in reference 9), signs of retrograde cell
loss are not necessarily "obligatory" (again, see
reference 36 and discussion in this paper.]

9b. Bauman M, Kemper TL. Histoanatomic observations of the brain in early infantile
autism. Neurol 35.866-74 1985.
9c. Bolton PF, Griffiths PD. Association of tuberous sclerosis of temporal lobes
with autism and atypical autism. Lancet 249.392-5 1997.
9d. Binstock TC. Hypothesis: Febrile seizures and the amygdala: a causal mechanism
in autism and related disorders. Bit.listserv.autism January 31, 1997.
9e. Bachevalier J. The contribution of medial temporal lobe structures in infantile
autism. pp 146-69 in: The Neurobiology of Autism. Bauman M, Kemper T, eds.
Baltimore: Johns Hopkins University Press, 1994.
9f. Macklis RM, Macklis JD. Historical and phrenologic reflections on the nonmotor
functions of the cerebellum: love under the tent? Neurol 42.928-32 1992.

10. Brodal A. Modification of Gudden method for study of cerebral localization. Arch
Neurol Psychiatr 43.46-58 1940.
"A peculiar characteristic of the reaction to damage of the
central nervous system of the newborn animal is its great
power of healing without leaving a scar, a feature of which
Gudden was aware and which has been verified by various
authors. Spatz... has shown that this is due to a difference
in the process of resorption of the destroyed parts in newborn
and adult specimens. The glia cells are more dense in newborn
animals, and they alone bring about repair, as there is little
myelin present. In adults, on the other hand, in which the
glial cells lie far apart and there are abundant masses of
myelin, mesodermal alements also take part in the resorption
and repair of the tissue. In this case, therefore, the result
is a scar of connective tissue, whereas in newborn animals
only a fine glial membrane indicates the place where the
continuity of tissue was once broken."
[This passage describes observations based upon knife
cuts, and sub-necrotic apoptosis -- especially in cases
wherein the neurons are lesioned by reasons other than knife-
cuts -- may yield neuronal death and disappearance without
scarring. See Bredesen cite (14) below and related discussion
in text.]

11. Norton WT, Aquino DA, Hozumi I, Chiu FC, Brosnan CF. Quantitative aspects of
reactive gliosis: a review. Neurochemical Research 17.877-85
1992.
12. Holmes G, Stewart TG. On the connection of the inferior olives with the
cerebellum in man. Brain 31.125-37 1908.
[Each of the cases described by Holmes involved major lesions
of the cerebellum, by surgery and/or by major damage caused by
illness or infection. Therefore, these cases are closer to
knife cuts that induce gliosis and may not be parallel to
apoptotic cerebellar lesions that do not induce necrosis.]

13. Charriaut-Marlange C, Aggoun-Aouaoui D, Represa A, Ben-Ari Y. Apoptotic features
of selective neuronal death in ischemia, epilepsy and gp120 toxicity. Trends in
Neurosciences 19.109-114 1996.

14. Bredesen DE. Neural apoptosis. Ann Neurol 38.839-51 1995.
"...virtually any insult just below the threshold to induce
necrosis may result in a cellular apoptotic response..." ** In
reviewing findings about several naturally occurring apoptosis
and anti-apoptosis proteins, Bredesen writes "...Purkinje
cells express relatively high levels of bax and very little
bcl-2, suggesting they may be particularly vulnerable to a
number of insults..." and similarly vulnerable is "the CA1
region of the hippocampus...".
With regard to 'scarring' and 'lack of scarring' in
neuronal tissues, the most significant principle described in
the Breeden paper may be, "...cells undergoing apoptosis in
vivo are phagocytosed, and although this may occur by cells of
the macrophage lineage, it may also occur by other neighboring
cells, leaving very little evidence that apoptosis has
occurred."
[If a postnatal lesion occurred via non-necrotic apoptosis,
then little, if any, scarring (eg, gliosis) would be evident.
In other words, lack of gliosis/scarring does not necessarily
prove "in utero" timing.]

15. O'Callaghan JP. Biochemical analysis of glial fibrillary acidic protein as a
quantitative approach to neurotoxicity assessment: advantages, disadvantages and
application to the assessment of NMDA receptor antagonist-induced neurotoxicity.
Psychopharmacology Bulletin 30.549-554 1994.
"On the basis of extensive reports in the literature of
trauma-induced glial scarring of the CNS..., one of our
initial assumptions was that toxicant-induced reactive gliosis
would also be a permanent condition. All of our results
suggest that, in general, chemical-induced injury of the CNS
results in a time-dependent, not a permanent gliosis, bases on
assays of GFAP. Moreover, the time-course of induction of GFAP
and its subsequent decline toward baseline vary markedly from
one toxicant to another."

16. Vohr BR, Lester B, Rapisardi G, O'Dea C, Brown L, Peucker M, Cashore W, Oh W.
Abnormal brain-stem function (brain-stem auditory evoked response) correlates with
acoustic cry features in term infants with hyperbilirubinemia. J Pediatr 115.303-8
1989.
17. Vorh BR, Rapisardi G, Karp D, O'Dea C, Lester B, Garcia-Coll C, Brown L, Oh W,
Cashore WJ. Behavioral changes correlated with cry characteristics and brainstem
auditory evoked responses (BAER) in term infants with moderate hyperbilirubinemia.
Ped Res abstract 99 p19a 1989.
18. Hara A, Hirose Y, Wang A, Yoshimi N, Tanaka T, Mori H. Localization of Bax and
Bcl-2 proteins, regulators of programmed cell death, in the human central nervous
system. Virchows Arch 429.249-53 1996.
19. Brown JK, Hussain IH. Status epilepticus. I: Pathogenesis. Dev Med Child Neurol
33.3-17 1991.
20. Maher J, McLachlan RS. Febrile convulsions: is seizure duration the most
important predictor of temporal lobe epilepsy? Brain 118.1521-8 1995.
21. Morikawa E, Ginsberg MD, Dietrich WD, Duncan RC, Kraydieh S, Globus MY, Busto
R. The significance of brain temperature in focal cerebral ischemia:
histopathological consequences of middle cerebral artery occlusion in the rat. J
Cereb Bl Flow Metab 12.380-9 1992.
22. Manning DJ, Rosenbloom L. Non-convulsive status epilepticus. Arch Dis Child
62.37-40 1987.
23. O'Donohoe NV. Epilepsies of Childhood. 3rd ed. Oxford: Butterworth- Heinemann
Ltd, 1994.
24. Patry G, Lyagoubi S, Tassinari CA. Subclinical "electrical status epilepticus"
induced by sleep in children: a clinical and electro- encephalographic study of six
cases. Arch Neurol 24.242-252 1971.
24a. Deonna TW. Acquired epileptiform aphasia in children (Landau- Kleffner
syndrome). J Clinical Neurophysiol 8.288-98 1991.
25. Sloviter RS, Dean E, Neubort S. Electron microscopic analysis of
andrenalectomy-induced hippocampal granule cell degeneration in the rat: apoptosis
in the adult central nervous system. J Comp Neurol 330.337-51 1993.
26. Buchanan KL, Yellon SM. Developmental study of GnRH neuronal projections to the
medial basal hypothalamus of the male Djungarian hamster. J Comp Neurol 333.236-45
1993.
27. DeLong GR, Bean SC, Brown III FR. Acquired reversible autistic syndrome in acute
encephalopathic illness in children. Arch Neurol 38.191-4 1981.
28. Ghaziuddin M, Tsai LY, Eilers L, Ghaziuddin N. Brief report: autism and herpes
simplex encephalitis. J Aut Dev Disord 22.107-13 1992.
29. Gillberg C. Brief report: onset at age 14 of a typical autistic syndrome. A case
report of a girl with herpes simplex encephalitis. J Aut Dev Disord 16.369-75 1986.
30. Belluardo N, Mudo G, Hiang XH, Condorelli DF. Induction of astroglial gene
expression by experimental seizures in the rat: spatio- temporal patterns of the
early stages. Glia 16.174-86 1996.
31. O'Callaghan PJ, Miller DB. Cerebellar hypoplasia in the Gunn rat is associated
with quantitative changes in neurotypic and gliotypic proteins. J Pharmacol Exp Ther
243.522-33 1985.
32. Baker SM, Pangborn J. Clinical Assessment Options for Children with Autism and
Related Disorders: A biomedical approach. San Diego, California: Autism Research
Institute, 1996.
33. Coulter HL. Vaccination, Social Violence, and Criminality: The medical assault
on the Americal brain. Center for Empirical Medicine; Washington, D.C.: North
Atlantic Books; Berkeley;, 1990.
34. Coulter HL, Fisher BL. A Shot in the Dark: Why the P in the DPT vaccination may
be hazardous to your child's health. Garden City Park, New York: Avery Publishing
Group Inc., 1991.
35. Roger C, Loziel V, Vert P, Nehlig A. Effects of bilirubin infusion on local
cerebral glucose utilization in the immature rat. Dev Brain Res 76.115-30 1993.
36. Marty S, Peschanski M. Effects of target deprivation on the morphology and
survival of adult dorsal column neurons. J Comp Neurol 356.523-36 1995.

*******

Teresa C. Binstock,
Researcher in Developmental & Behavioral Neuroanatomy
Denver
(c) 1997

end of part 4 of 4
POSTING HISTORY FOR CRITIQUE OF BAUMAN/KEMPER SPECULATIONS

>>> Posting number 13491, dated 11 May 1997 20:09:12
Date: Sun, 11 May 1997 20:09:12 -0600
Sender: SJU Autism and Developmental Disablities List
From: Teresa Binstock
Subject: 0 Changing the autism paradigm re: timing (announcement)

.....announcement about paper.....
The following paper shall be coming thru the e-pipeline and presents a rationale
asserting that recently published studies suggest that Bauman's and Kemper's
rationales about in-utero timing need to be reconsidered.

ti: Changing the autism paradigm: a critique of Kemper & Bauman's
speculations regarding in-utero timing.
au: Teresa C. Binstock
so: Bit.listserv.autism 5.11.97

to be posted with subject headings:
1 Changing the autism paradigm re: timing (part 1 of 4)
2 Changing the autism paradigm re: timing (part 2 or 4)
3 Changing the autism paradigm re: timing (part 3 of 4)
4 Changing the autism paradigm re: timing (part 4 of 4)

>>> Posting number 13493, dated 11 May 1997 20:11:30
Date: Sun, 11 May 1997 20:11:30 -0600
Sender: SJU Autism and Developmental Disablities List
From: Teresa Binstock
Subject: 1 Changing the autism paradigm re: timing

>>> Posting number 13494, dated 11 May 1997 20:16:39
Date: Sun, 11 May 1997 20:16:39 -0600
Sender: SJU Autism and Developmental Disablities List
From: Teresa Binstock
Subject: 2 Changing the autism paradigm re: timing

>>> Posting number 13495, dated 11 May 1997 20:19:51
Date: Sun, 11 May 1997 20:19:51 -0600
Sender: SJU Autism and Developmental Disablities List
From: Teresa Binstock
Subject: 3 Changing the autism paradigm re: timing

>>> Posting number 13496, dated 11 May 1997 20:24:26
Date: Sun, 11 May 1997 20:24:26 -0600
Sender: SJU Autism and Developmental Disablities List
From: Teresa Binstock
Subject: 4 Changing the autism paradigm re: timing

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