3 -  Vulnerability of the auditory system
Despite the protective feedback mechanisms that
most often prevent damage to the inferior colliculus,
the inferior colliculus is involved in brain damage from
many causes.  The resemblance of damage to
Wernicke's encephalopathy has on rare occasions
been noted [1, 2].  Wernicke-like pathology is often
the result of catastrophic situations in which protective
mechanisms have no chance to go into effect.  Rapid
intoxication with alcohol, inhalation of poisons like
methyl bromide, and asphyxia by suffocation or
cardiac arrest are all catastrophic events [3. 4].

Deficiency of thiamine (vitamin B1) is among the best
known causes of brain damage involving the inferior
colliculi.  Figure 13 is from the paper by Vortmeyer et
al. (1992) and shows severe hemorrhagic damage in
the inferior colliculi of a terminally ill person
maintained on parenteral (intravenous) feeding
lacking thiamine supplement [5].  Thiamine is an
essential cofactor for several enzymes that catalyze
aerobic metabolism; its importance is discussed
further in the following chapters.  Rapid depletion of
thiamine during maintenance on intravenous feeding
can also be considered a catastrophic event, barely
less serious than suffocation.

Aerobic metabolism is totally disabled when cofactors
like thiamine for aerobic enzymes are removed, or
when these enzymes are damaged by poisonous
substances.  The hazards of environmental toxins
such as mercury and lead are currently receiving a
good deal of attention.  Direct poisoning or denaturing
of aerobic enzymes is as catastrophic an event as
depletion of cofactors or asphyxia.  Protective
biofeedback mechanisms cannot preserve metabolic
functions in brain areas of high metabolic rate if the
enzymes that accomplish metabolic transformations
are rendered non-functional.

Oyanagi et al. (1989) examined the brains of fourteen
people who died from exposure to methyl mercury [6].  
These patients exhibited signs of Hunter-Russell
syndrome (or Minamata disease) which includes
ataxia and impairments of hearing and speech, and is
known to involve damage of the auditory receptive
areas of the temporal lobes.  Oyanagi et al. found
degeneration of auditory nuclei in the brainstem in
addition to temporal lobe damage.

Sokoloff et al. (1977) modified the autoradiographic
method for measuring blood flow to measure glucose
uptake [7] .  They used radioactive deoxyglucose as
the tracer, which is taken up in the brain like glucose
but not metabolized further.  This method has been
used by many researchers to study changes in
metabolism resulting from drugs and other factors that
impair brain function.

Bertoni and Sprenkle (1988) investigated the effects
of lead poisoning in laboratory rats by measuring its
effects on glucose uptake in the brain [8].  They found
a decrease in cerebral metabolism throughout the
brain, which was most significant in auditory nuclei of
the brainstem.  Burchfield and Abrams (1993) also
used the deoxyglucose method to investigate the
effects of cocaine on fetal sheep [9].  They noted a
reduction of glucose uptake in all regions of the brain,
except in frontal gyri of some of the experimental
animals.  However, the data they present indicate the
greatest reduction in brainstem nuclei of highest
metabolic rate such as the inferior colliculus, inferior
olives, and mammillary bodies.

Reports of brain damage caused by the toxic
substance methyl bromide made special note of
serious involvement of the inferior colliculi [3, 10, 11].  
Alpha-chlorohydrin is a chemical substance once
under development as a male contraceptive, until its
unacceptable side-effects were discovered [12].  It
has since been found to cause precisely localized,
symmetrical damage limited to the inferior colliculi,
superior olives, and red nuclei in experimental
animals.  By increasing the dose or giving repeated
small doses more widespread damage could be
produced.

The anti-cancer drug, Carboplatin has been found to
damage the inferior colliculi [13].  The antimicrobial
drug metronidazol (Flagyl) was found in one study to
cause a Wernicke-encephalopathy-like pattern of
damage in rats that involved the superior rather than
the inferior colliculi [14].  An experimental anti-tumor
drug, erbulozole, caused clinical signs of Wernicke
encephalopathy in two human patients  [16, 17].  Use
of the deoxyglucose method might be prudent in the
testing of chemical substances used widely for any
purpose, but especially those used as medications.

The auditory system and other brainstem nuclei of
high metabolic rate have been shown in the reports
mentioned above to be selectively vulnerable to toxic
substances as well as asphyxia.  This vulnerability is
discussed in more detail in the chapters that follow.  
The high rate of cerebral blood flow exposes nuclei in
the auditory system to greater amounts of circulating
toxins, and sooner than less well perfused areas of
the brain.  The auditory system is clearly vulnerable to
many noxious factors, and impairment of auditory
function would seem likely to be involved in cases of
autism resulting from toxins or infections that disrupt
brain metabolism during early development.

A popular theory is that use of lead (plumbing) in
aqueducts and drinking of wine from lead vessels may
have led to the fall of the Roman Empire.  An alarming
rise in cases of autism has become evident in recent
years and an association of autism with prenatal
exposure to alcohol, "recreational" drugs, prescribed
medications such as valproic acid, and vaccines
preserved with mercury compounds.  Could ignorance
of the hazards of toxic chemicals lead to the fall of our
own civilization?
  1. Neubuerger KT (1954)
    Lesions of the human
    brain following circulatory
    arrest.
  2. Vortmeyer AO et al.
    (1993) Hypoxia-ischemia
    and thiamine deficiency.
  3. Goulon M et al. (1975).
    Intoxication par le
    bromure de methyl: Trois
    observations, dont une
    mortelle.  Etude neuro-
    pathologique d'un cas de
    stupeur avec myoclonies,
    suivi pendent cinq ans.
  4. Janzer RC & Friede RL
    (1980) Hypotensive brain
    stem necrosis or cardiac
    arrest encephalopathy?
  5. Vortmeyer AO et al.
    (1992) Haemorrhagic
    thiamine deficient
    encephalopathy following
    prolonged parenteral
    nutrition.
  6. Oyanagi K et al. (1989).
    The auditory system in
    methyl mercurial
    intoxication: a
    neuropathological
    investigation on 14
    autopsy cases in Niigata,
    Japan.
  7. Sokoloff L et al. (1977)
    The [14C]deoxyglucose
    method for the
    measurement of local
    cerebral glucose
    utilization: theory,
    procedure, and normal
    values in the conscious
    and anesthetized albino
    rat.
  8. Bertoni JM and Sprenkle
    PM (1989) Lead acutely
    reduces glucose utilization
    in the rat brain especially
    in higher auditory centers.
  9. Burchfield DJ & Abrams
    RM (1993). Cocaine
    depresses cerebral
    glucose utilization in fetal
    sheep.
  10. Franken L (1959) Étude
    anatomique d'un cas
    d'intoxication par le
    bromure de méthyle.
  11. Squier MV et al. (1992)
    Case report:
    neuropathology of methyl
    bromide intoxication.
  12. Cavanagh JB & Nolan CC
    (1993) The neurotoxicity
    of alpha-chlorohydrin in
    rats and mice: II. Lesion
    topography and factors in
    selective vulnerability in
    acute energy deprivation
    syndromes.  
  13. Husain K, Whitworth C,
    Hazelrigg S, Rybak L
    (2003) Carboplatin-
    induced oxidative injury in
    rat inferior colliculus.  Int J
    Toxicol. 2003 Sep-Oct;22
    (5):335-42.
  14. Rogulja P et al. (1973)
    Metronidazol-
    Encephalopathie der
    Ratte.
  15. DeKlippel N et al. (1991)
    A Wernicke's
    encephalopathy-like
    neurotoxicity induced by
    erbulozole.
  16.  Van Belle SJ et al.
    (1993) Phase I trial of
    erbulozole (R55104).
  17. Waldron HA. Lead
    poisoning in the ancient
    world. Med Hist. 1973 Oct;
    17(4):391-9.
  18. Eisinger J.  Lead and
    wine. Eberhard Gockel
    and the colica Pictonum.
    Med Hist. 1982 Jul;26(3):
    279-302.
top
Figure 13 - From Vortmeyer et al. (1992)
Damage to the inferior colliculi
in a human patient maintained
on prolonged parenteral feeding
lacking vitamin B1
                       Hemorrhagic
damage of the inferior colliculi
from thiamine deficiency.
Figure 13:
References
Full References & Notes
  1. Neubuerger KT (1954) Lesions of the human brain following circulatory arrest.  
    Journal of Neuropathology and Experimental Neurology 13:144-160.
  2. Vortmeyer AO, Hagel C, Laas R (1993) Hypoxia-ischemia and thiamine deficiency.
    Clin Neuropathol. 1993 Jul-Aug;12(4):184-90.
  3. Goulon M, Nouailhat R, Escourolle R, Zarranz-Imirizaldu JJ, Grosbuis S, Levy-
    Alcover MA (1975). Intoxication par le bromure de methyl: Trois observations, dont
    une mortelle.  Etude neuro-pathologique d'un cas de stupeur avec myoclonies,
    suivi pendent cinq ans.  Revue Neurologique (Paris) 131:445-468.
  4. Janzer RC, Friede RL. Hypotensive brain stem necrosis or cardiac arrest
    encephalopathy? Acta Neuropathol (Berl). 1980;50(1):53-6.
  5. Vortmeyer AO, Hagel C, Laas R (1992) Haemorrhagic thiamine deficient
    encephalopathy following prolonged parenteral nutrition. Journal of Neurology,
    Neurosurgery and Psychiatry 55:826-829.
  6. Oyanagi K, Ohama E, and Ikuta F (1989). The auditory system in methyl mercurial
    intoxication: a neuropathological investigation on 14 autopsy cases in Niigata,
    Japan.  Acta Neuropathologica (Berlin). 77:561-568.
  7. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD,
    Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the
    measurement of local cerebral glucose utilization: theory, procedure, and normal
    values in the conscious and anesthetized albino rat. Journal of Neurochemistry 28:
    897-916.
  8. Bertoni JM and Sprenkle PM (1989) Lead acutely reduces glucose utilization in the
    rat brain especially in higher auditory centers.  Neurotoxicology 9:235-242.
  9. Burchfield DJ, Abrams RM (1993). Cocaine depresses cerebral glucose utilization
    in fetal sheep.  Developmental Brain Research 73:283-288.
  10. Franken L (1959) Étude anatomique d'un cas d'intoxication par le bromure de
    méthyle. Acta Neurologica et Psychiatrica Belgica 59:375-383.
  11. Squier MV, Thompson J, Rajgopalan B. (1992) Case report: neuropathology of
    methyl bromide intoxication. Neuropathology and Applied Neurobiology 18: 579-
    584.
  12. Cavanagh JB, Nolan CC (1993) The neurotoxicity of alpha-chlorohydrin in rats
    and mice: II. Lesion topography and factors in selective vulnerability in acute
    energy deprivation syndromes.  Neuropathology and Applied Neurobiology 19:471-
    479.
  13. Husain K, Whitworth C, Hazelrigg S, Rybak L (2003) Carboplatin-induced oxidative
    injury in rat inferior colliculus.  Int J Toxicol. 2003 Sep-Oct;22(5):335-42.
  14. Rogulja P von, Kovac W, Schmid H (1973) Metronidazol-Encephalopathie der
    Ratte. Acta Neuropathologica (Berlin) 25:36-45.
  15. DeKlippel N, De Keyser J, De Greve J, Van Belle S (1991) A Wernicke's
    encephalopathy-like neurotoxicity induced by erbulozole. Neurology 41:762-3.
  16. Van Belle SJ, Distelmans W, Vandebroek J, Bruynseels J, Van Ginckel R, Storme
    GA. Phase I trial of erbulozole (R55104). Anticancer Res. 1993 Nov-Dec;13(6B):
    2389-91.
  17. Waldron HA. Lead poisoning in the ancient world. Med Hist. 1973 Oct;17(4):391-9.
  18. Eisinger J.  Lead and wine. Eberhard Gockel and the colica Pictonum. Med Hist.
    1982 Jul;26(3):279-302.