- Scremin OU, Shih TM, Corcoran KD (1991) Cerebral blood flow-metabolism coupling after
administration of soman at nontoxic levels. Brain Research Bulletin 26:353-6.
- Kant F (1933) Die Pseudoencephalitis Wernicke der Alkoholiker. (polio-encephalitis
haemorrhagica superior acuta). Archiv für Psychiatrie und Nervenkrankheiten 98:702-768.
- Bini L and Bollea G (1947). Fatal poisoning by lead-benzine (a clinico-pathologic study).
Journal of Neuropathology and Experimental Neurology 6:271-285.
- Franken L (1959) Étude anatomique d'un cas d'intoxication par le bromure de méthyle. Acta
Neurologica et Psychiatrica Belgica 59:375-383.
- 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.
- Squier MV, Thompson J, Rajgopalan B. (1992) Case report: neuropathology of methyl bromide
intoxication. Neuropathology and Applied Neurobiology 18: 579-584.
6 - Catastrophic impairment
Wernicke-like patterns of damage that involve the
inferior colliculus and other brainstem nuclei of high
metabolic rate have been reported in the brains of
people who survive for a period of time after inhalation
of chemical fumes. Different substances may have
their effect on different enzymes in the aerobic
metabolic cycle; there are many more enzymes and
enzyme-complexes in the chain of biochemical
reactions required for energy production that are not
dependent on thiamine. Some toxins might damage
other essential mechanisms required for metabolic
integrity, such as transport proteins at the capillary-to-
neuron interface. The more toxic a substance, the
more immediately it will act. Variability from one case
to another in the sites of damage depends on whether
protective biofeedback mechanisms have a chance to
go into action.
Use of the autoradiographic methods for blood flow
and deoxyglucose uptake should help elucidate the
mechanisms and time-course of toxic exposure. For
example, Scremin et al. (1991) found in laboratory rats
that sub-lethal exposure to the chemical nerve gas
Soman increased glucose uptake in the superior
colliculi with decreased blood flow and glucose uptake
in all other brain regions. Kant (1933) noted
involvement of the superior colliculi in several people
who died from chronic alcohol use, and he commented
that this was less usual than damage to the inferior
colliculi. The less metabolically active superior colliculi
will be more vulnerable in circumstances in which
feedback mechanisms have time to go into action to
maintain integrity of biochemical systems in the inferior
colliculi.
Bini and Bollea (1947) described a confusional
delirium, which they compared to alcoholic intoxication,
in two pressers in a dry-cleaning establishment who
suffered chronic intoxication by fumes of cleaning
fluids. Both died after lapsing into coma, and the focal
lesions typical of Wernicke's encephalopathy were
found in the mammillary bodies, floor of the fourth
ventricle, and the inferior and superior colliculi.
Methyl bromide was used as a fire extinguisher in
France until its use was found responsible for several
deaths. The effects of methyl bromide are far more
catastrophic than dry cleaning fumes or alcohol
intoxication. Franken (1959) found lesions of the
inferior colliculi with milder involvement of the
mammillary bodies in a man who had worked for two
years filling fire extinguishers with methyl bromide.
Goulon et al. (1975) described clinical symptoms that
developed after methyl bromide intoxication in three
people, and the neuropathology found post-mortem in
one of these. Methyl bromide led to a vegetative state
in all three individuals. The patient whose brain was
examined on autopsy revealed a bilateral pattern of
damage confined to the brainstem, with the most
prominent damage found in the inferior colliculi.
Squier et al. (1992) reported the cases of a man and
his pet dog both poisoned by methyl bromide from a
leaky fire extinguisher. The man found his dog dead.
Later the man became confused, suffered grand mal
seizures, fell into a coma, and died 30 days later. The
main finding in the brain of the dog was marked
edema of the cerebral cortex. In the man’s brain the
mammillary bodies and inferior colliculi were severely
affected; signs of damage were also noted in the
cerebellar dentate nuclei. Squier et al. commented on
the similarity of this pattern of damage to Wernicke’s
encephalopathy. They cited references to studies of
the neurotoxicity of methyl iodide, which is thought to
interfere with pyruvate metabolism, and suggested this
as the reason the damage caused by methyl bromide
is similar to that caused by thiamine deficiency.
The dog died within hours at most after being
overcome with methyl bromide, and this may explain
the difference in how the brain was affected. Whether
from alcohol intoxication or exposure to any other toxic
substance, the distinctive pattern of Wernicke’s
encephalopathy appears to develop only if the victim
survives for a week or more after the event. Wernicke’
s encephalopathy may be the result of a process in
which compensatory mechanisms are set in action, but
fail to restore the brainstem nuclei of high metabolic
rate to their normal functioning state.
- Scremin OU, Shih TM,
Corcoran KD (1991)
Cerebral blood flow-
metabolism coupling after
administration of soman at
nontoxic levels. Brain
Research Bulletin 26:353-6.
- Kant F (1933) Die
Pseudoencephalitis
Wernicke der Alkoholiker.
(polio-encephalitis
haemorrhagica superior
acuta). Archiv für Psychiatrie
und Nervenkrankheiten 98:
702-768.
- Bini L and Bollea G (1947).
Fatal poisoning by lead-
benzine (a clinico-pathologic
study). Journal of
Neuropathology and
Experimental Neurology 6:
271-285.
- Franken L (1959) Étude
anatomique d'un cas
d'intoxication par le bromure
de méthyle. Acta Neurologica
et Psychiatrica Belgica 59:
375-383.
- 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.
- Squier MV, Thompson J,
Rajgopalan B. (1992) Case
report: neuropathology of
methyl bromide intoxication.
Neuropathology and Applied
Neurobiology 18: 579-584.