1 - Creak (1963) and Williams et al. (1980)
Brain damage in cases of autism is either
widespread or difficult to detect at all. Creak (1963)
described investigations of the brain in four patients
with autistic behaviors [1]. One child had tuberous
sclerosis, which was confirmed at autopsy. Two
patients had been followed into their twenties as part
of a group believed to have no organic basis for their
developmental problems, and it was a surprise to find
at autopsy that both had widespread neurolipidosis.
Creak’s fourth patient died during a seizure at age
ten, and that no abnormality was found in her brain
again came as a surprise.
Williams et al. (1980) examined the brain in four
autistic subjects who were all also mentally retarded [2]
. Reduced Purkinje cell density was noted in the
cerebellum of a male patient who had a chronic
seizure disorder and died at age twelve. This patient
also had reduced pyramidal cell dendrites in the
midfrontal gyrus. The same pyramidal cell
abnormality was seen in the brain of a 27-year old
subject who belatedly was found to have
phenylketonuria (PKU), and this was the only
abnormality found. A female patient had developed
normally up to 20 months of age, but then regressed
and died at age three; no abnormality was seen in her
brain. She perhaps had Rett syndrome or a
mitochondrial disorder but died before microcephaly
or other visible pathological changes became evident.
Because two of the four cases they investigated
had suffered perinatal problems, Williams et al. (1980)
made a special effort to look for changes in the
tectum (inferior colliculi) of the kind reported by
Windle (1969) and Myers (1972) in monkeys
subjected to asphyxia at birth [4, 5]. No visible or
microscopic signs of cell loss or gliosis could be found
in this area in any of the brains; therefore, the
perinatal compromise in these cases could not have
been as severe as that found by Windle or Myers.
One of these was the patient who died at age twelve.
The second died during a seizure at age 33; he had
been paraplegic since age 16 from a poliovirus
infection, and the expected depletion of anterior horn
cells in the spinal cord was noted. Otherwise focal
areas of atrophy were seen in the orbito-frontal and
anterior temporal regions in both cases but were
attributed to head trauma that occurred after the
appearance of autistic symptoms.
Williams et al. (1980) noted that the brain weights
for all four subjects were within normal limits for age,
and they concluded that autism in their four cases
resulted from abnormal metabolic influences that do
not visibly alter the structure of the nervous system.
They suggested dysfunction in a common anatomic
pathway is responsible for autistic behaviors because
they occur in such wide a variety of disorders.
The articles by Creak (1963) and Williams et al.
(1980) indicate that even in cases of serious mental
handicap it is not always possible to detect visible
signs of brain damage. Impairment of function in these
cases must result from derangement of biochemical
processes. On the other hand, that autistic behaviors
were seen in cases of tuberous sclerosis,
neurolipidosis, and phenylketonuria means that the
submicroscopic disruption of function that causes the
core syndrome of autism can be produced by
disorders that also affect wide areas of the brain.
Lipid deposits in neurons may result from defects of
mitochondrial aerobic function. Transport of fatty
acids into the cell may occur as an alternative to failed
glucose metabolism. Creak noted that neurolipidosis
was a process which must have been going on for
many years. In the early stages, the auditory system
could be expected to be most susceptible to altered
function because its metabolic requirements exceed
those of other brain areas.
- Creak M (1963) Childhood
psychosis: A review of 100
cases.
- Williams RS et al. (1980)
Autism and mental
retardation: Neuropathologic
studies performed in four
retarded persons with
autistic behavior.
- Windle WF (1969) Brain
damage by asphyxia at birth.
- Myers RE (1972) Two
patterns of perinatal brain
damage and their conditions
of occurrence..
- Creak M (1963) Childhood psychosis: A review of 100 cases. British Journal of Psychiatry 109:
84-89.
- Williams RS, Hauser S, Purpura DP, deLong GR, Swisher CN (1980) Autism and mental
retardation: Neuropathologic studies performed in four retarded persons with autistic
behavior. Archives of Neurology 37:748-753.
- Windle WF (1969) Brain damage by asphyxia at birth. Scientific American 221(#4):76-84.
- Myers RE (1972) Two patterns of perinatal brain damage and their conditions of occurrence.
American Journal of Obstetrics and Gynecology 112:246-276..
Case 1 – Female, age 3
Brain: Tuberous sclerosis.
Clinical: Normal development during first year. Backwardness in
speech. Petit mal seizures.
Case 2 – Male, age 28
Brain: Externally normal, widespread neurolipidosis found on section.
Clinical: Elder sibling died at birth. Labor induced because of pelvic
contracture, forceps delivery. Speech began at 14 months, but no
progress after 4 years. Withdrawal between ages 3 and 4.
Case 3 – Male, age 25
Brain: Externally normal, widespread neurolipidosis found on section.
Clinical: Breech birth. Normal development to age two, when his elder
brother died. The elder brother was severely spastic.
Case 4 – Female, age 10
Brain: Normal.
Clinical: Psychotic from early childhood. She died during her first seizure.
Case 1 – Male, age 33
Brain: Weight 1520 g. Focal areas of atrophy in orbito-frontal and
anterior temporal cortex.
Clinical: Third trimester toxemia of pregnancy. Prolonged labor and high
forceps delivery. Walked at 14 months and toilet trained during second
year. No speech at 30 months. Concussion at age 4. Institutionalized at
age 11, single words and short phrases. Poliomyelitis at age 16 with
subsequent paraplegia. Grand mal seizure at age 30, second seizure at
33 lead to aspiration and death.
Case 2 – Female, age 3
Brain: Weight 1200 g. No abnormalities.
Clinical: Sat at 7 months, walked at 15 months, toilet trained during
second year
Single words at 15 months, short phrases by 18 months. Regression
beginning at 20 months led to mutism and clumsy gait. Fascination with
submerging in water led to drowning at 36 months.
Case 3 - Male, age 12
Brain: Weight 1430 g. Focal areas of cortical atrophy in orbito-frontal
and anterior temporal regions (as in case 1). Density of Purkinje’s cells
reduced generally within the cerebellum. Reduced density of spines on
dendrites of pyramidal neurons.
Clinical: Respiratory distress within first few minutes after birth. Oxygen
administered intermittently during next 24 hours. Surgical repair of
inguinal hernia at 3 months. Frequent respiratory infections during the
first year. Reached for objects at 2 to 3 months, sat at 7 months, then
subsequent delay. Crawled at 16 months, walked at 24 months.
Neurologic exam at 25 months, head circumference 51 cm (90th
percentile). Auditory acuity judged normal, but did not startle to loud
noise Never developed communicative skills. Gait remained unsteady,
and he was not toilet trained. Seizures began at age 5. Death during
sleep at age 12. His younger sister was also mentally retarded,
speechless, had seizures, died at age 7 – no gross or microscopic brain
abnormalities found. An older sister was normal.
Case 4 - Male, age 27
Brain: Weight 1240 g. Reduced density of dendritic spines on pyramidal
neurons.
Clinical: Prolonged labor, low forceps delivery. Development normal for
first six months, delayed milestones thereafter. Did not walk until early in
his third year. Failed to acquire speech or other communicative skills.
Institutionalized at age eight. Microcephaly at age 12 (53cm, 25th
percentile). Phenylketonuria diagnosed at age 21. Death from
aspiration pneumonia at age 27.
Notes on postmortem findings of Williams et al. (1980)
Notes on postmortem findings of Creak (1963)