29. Selected Highlights
      The viewpoint presented in this book cites references that span a
time-period of 125 years.  Autistic disorder is caused by impairment
within the brain, hence many discoveries that have led to better
understanding of the brain are relevant, and especially those that clarify
function within circuits for hearing and language.  Factors that make the
brain vulnerable to damage and conditions that compromise metabolism
in the brain also have relevance for understanding autism.  Parallel
discoveries about bacterial infections, causes of mental disorders like
dementia paralytica, phenylketonuria, and pathology caused by defects
of the aerobic enzymes in mitochondria are useful to know about in terms
of how knowledge is acquired and incorporated into a common cultural
understanding, even if not directly related to causes of most cases of
autism.
      Following is a list of some selected highlights with special relevance
to issues discussed in this book:

• Wernicke (1874) proposed a theory of aphasic disorders caused
  by disruption of the neural circuit connecting the speech motor
  and auditory receptive areas of the cerebral cortex.
  
• Gayet (1875) described symmetric bilateral damage of brainstem
  areas in a man who survived scalding of the airways for five
  months.
  
• Wernicke (1881) described symmetric bilateral lesions within the
  brainstem similar to that reported by Gayet in two alcoholic men
  and a woman poisoned by sulfuric acid; this pattern of damage is
  known as “Wernicke’s encephalopathy,” “Gayet-Wernicke
  encephalopathy,” and the neurological signs (oculomotor, ataxia,
  etc.) as "Wernicke-Korsakoff syndrome."
  
• Korsakoff  (1889) reported signs of Wernicke's encephalopathy in
  additional cases of non-alcoholic origin: post-partum illnesses,
  typhoid, tuberculosis, tapeworm, diabetes, pneumonia, jaundice,
  and intestinal disorders.  He further described the long-term
  course leading to memory impairment.
  
• Kraepelin (1900) described clinical features of premature
  dementing mental illnesses and coined the term “dementia
  praecox,” later supplanted by the euphemism “schizophrenia.”
  
• Bohr (1904) obtained laboratory data on binding and release of
  oxygen by hemoglobin.
  
• Heller (1908) and DeSanctis (1908) using Kraepelin’s terminology
  described cases of “dementia infantilis.”
  
• Noguchi (1913) discovered the spirochete bacterium of syphilis in
  brains of people who died of dementia paralytica, one of the most
  prevalent mental illnesses until the cure, penicillin was discovered
  in 1943.
  
• Craigie (1920) determined that blood supply in the brain was
  highest in brainstem auditory nuclei.
  
• Gamper (1928) described Wernicke’s encephalopathy in 16 cases
  caused by alcohol intoxication.
  
• Kant (1933) described Wernicke’s encephalopathy in 17 cases
  caused by alcohol abuse.
  
• Zimmerman & Yannet (1933) described damage of the subcortical
  basal ganglia caused by jaundice (kernicterus) in infants.
  
• Langworthy (1933) investigated the time course of myelin
  development and noted its early appearance in the auditory
  system.
  
• Folling (1934) discovered abnormal metabolites of phenylalanine
  in the urine of two mentally retarded children.  Phenylketonuria
  (PKU), the result of a faulty enzyme in the liver was the first of the
  inborn errors of metabolism to be identified.
  
• Rosanoff et al. (1934) investigated "so-called schizophrenia" in
  twins and reported similarity of psychotic manifestations in both of
  monozygotic twin pairs was the exception rather than the rule.
  
• Peters (1936) performed experiments revealing thiamine (vitamin
  B1) to be an essential co-factor for aerobic metabolism of glucose.
  
• Krebs (1937) worked out the individual steps that make up the
  aerobic cycle for glucose metabolism (the Krebs cycle, or citric
  acid cycle).
  
• Neubürger (1937) reported Wernicke's encephalopathy
  associated with degenerative diseases of the gastrointestinal tract,
  liver, and kidneys not related to alcohol intoxication.  He
  suggested internally produced toxins caused the brain damage.
  
• Evans et al. (1942) reported a Wernicke-like pattern of brain
  damage in foxes raised for fur production and fed a diet of raw fish
  that lacked thiamine.
  
• Kanner (1943) described infantile autism.
  
• Asperger (1944) described youth unable to participate in shared
  work projects.
  
• Leigh (1951) described Wernicke-like neuropathology in a child
  who died of what was thought to be an encephalitic process, but
  now believed caused by defective enzymes for aerobic metabolism
  in mitochondria.
  
• Neubuerger (1954) reported Wernicke-like neuropathology in
  patients who survived at least several days after resuscitation from
  cardiac arrest.
  
• Landau et al (1955) measured blood flow in the brain with an inert
  radioactive tracer and found the highest flow rates in the auditory
  system, especially the inferior colliculus.
  
• Ranck & Windle (1959) reported selective damage of the inferior
  colliculus in five monkeys who survived resuscitation following
  asphyxia at birth.
  
• Gellner (1959) proposed the inferior and superior colliculi as the
  site of impairment of social function in cases of mental retardation.
  
• Ross (1959) reported a Wernicke-like pattern of brain damage in
  a child with autistic behaviors possibly caused by anorexia and
  nutritional deficiencies.
  
• Landau et al. (1960) described bilateral subcortical brain damage
  in a case of childhood aphasia, with moset severe involvement of
  the medial geniculate bodies of the auditory system.
  
• Gross and Kaltenbach (1960) reported a larger than normal brain
  and damage of the inferior olives in a case of Heller’s syndrome.
  
• Roth & Barlow (1961) used radioactive labeled anesthetic drugs to
  determine sites of action in the brain and found that fast-acting
  thiopental accumulates in the inferior colliculi.
  
• Rozdilsky & Olszewski (1961) found bilirubin stains neurons in the
  inferior colliculus most heavily in experimental jaundice
  (kernicterus) of newborn cats and dogs.
  
• Kety (1962) reviewed the autoradiographic data showing the
  greatest blood flow in the inferior colliculi.
  
• Denny-Brown (1962) proposed that the superior colliculi might be
  the most essential structure in the brain for unitary function of the
  organism.
  
• Gilles (1963) reported brainstem damage in an infant resuscitated
  from drowning, noting similarity to that found by Ranck & Windle
  (1959), and proposed that damage of the inferior colliculi could be
  the cause of developmental language disorders.
  
• Creak (1963) reported neuropathological findings in four autistic
  patients.
  
• Lucey et al. (1964) found bilirubin stains neurons in the inferior
  colliculus and other brainstem nuclei only in concert with asphyxia.
  
• Brown & Bellugi (1964) proposed that children hear units of
  meaning in speech through recognition of stressed syllables.
  
• Rimland (1964) proposed a disorder of the brainstem reticular
  formation in autism.
  
• Yakovlev & Lecours (1967) confirmed the finding of Langworthy
  (1933) that the auditory system of the human brain is the earliest
  to become fully myelinated.
  
• Reivich et al. (1969) refined the autoradiographic method for
  measuring cerebral blood flow.
  
• Fisch (1970) proposed that hearing is the sense that keeps us
  most continually in touch with our environment, even during sleep.
  
• Geschwind (1970) proposed ways of testing impairment of brain
  circuits involved in language understanding and production.
  
• Chess (1971) reported autistic disorder in children affected by
  prenatal rubella infection.
  
• Myers (1972) discovered that a brief acute episode of asphyxia at
  birth damages the inferior colliculi and other brainstem sites and
  that the cerebral cortex becomes involved during a prolonged
  period of partial oxygen insufficiency.
  
• Miller & Myers (1972) reported the same patterns of brainstem or
  cortical damage in adult monkeys that Myers (1972) found with
  total or partial oxygen deprivation in the perinatal period.
  
• Sokoloff et al. (1977) refined the autoradiographic method for
  measuring cerebral blood flow for determining regional differences
  in glucose uptake and found the inferior colliculi to have the
  highest rate of glucose uptake in the brain.
  
• Ornitz (1983) Proposed a brainstem theory of autism.
  
• Ritvo et al (1986) reported neuropathology in four cases of autism
  and found decreased Purkinje cells in the cerebellum of all.
  
• Cavanagh & Harding (1994) reported neuropathology in 20 cases
  of Leigh’s syndrome with prominent damage in the inferior colliculi
  and other brainstem nuclei of high metabolic rate.
  
• Moore et al (1995) confirmed the finding of Yakovlev & Lecours
  (1967) that the auditory system of the brain is the earliest to
  become myelinated and is functional by 29 weeks of gestation.
  
• Gillberg & Coleman (1996) reviewed the diverse medical
  conditions associated with autism.
  
• Rapin (1997) proposed “verbal auditory agnosia” as cause of
  developmental language disorder in some children with autism.
  
• Kemper & Baumann (1998) reported neuropathology in nine
  cases of autism, which included many of the brainstem sites
  affected in Wernicke’s encephalopathy.