3 -  Wernicke's encephalopathy
Wernicke (1881a) discovered symmetric bilateral
damage of brainstem areas in a young woman who
died several months after ingesting sulfuric acid, and
he found the same bilateral pattern of damage in the
brains of two men who had been chronic users of
alcohol to the point of intoxication [1, 2].  The
brainstem centers affected were the same nuclei of
high metabolic rate later identified through use of the
autoradiographic techniques for blood flow and
deoxyglucose uptake.  Note that the finding of
brainstem damage caused by intoxication was a new
discovery not directly related to Wernicke's earlier
analysis (in 1874) of cortical association tracts
involved in aphasic disorders [3].

Bilateral involvement of the brainstem nuclei of high
metabolic rate has become a well recognized pattern
of pathology known as Wernicke's encephalopathy.  
Wernicke’s observations have been confirmed by
many subsequent investigators [4-9].  This brainstem
pattern is most often associated with chronic alcohol
abuse, but can also be caused by deficiency of vitamin
B1 (thiamine).  Wernicke-like patterns of damage have
further increasingly been noted in cases where death
resulted from exposure to toxic substances [10-12].

Figure 9 depicts a midline view of the brain and
brainstem structures affected in Wernicke's
encephalopathy.  The mammillary bodies are usually
most prominently affected, but the oculomotor nuclei,
inferior colliculi, inferior olives, and cerebellum are
also often damaged.  The pattern and degree of
involvement of these structures varies from case to
case.  Variability in vulnerability can best be explained
in terms of the protective feedback mechanisms that
go into action during a chronic course of exposure to
alcohol or any other situation that impairs cerebral
metabolism.

If the high rate of metabolism in the inferior colliculus
supports some crucial function for survival (auditory
attention, orientation, awareness, or even
consciousness), evolutionary adaptations may have
led to development of mechanisms to prevent lapses
in function.  Metabolic rate in the mammillary bodies is
not as high, and consolidation of short-term to long-
term memory may not be as immediately essential for
survival as auditory surveillance; thus the memory
consolidation function will suffer in favor of systems
that sense changes in the environment.

Protective mechanisms often involve vasodilation to
increase blood supply [13, 14].  The same mechanism
also leads to the swollen red "whiskey nose" of chronic
alcoholics.  If the protective dilation of blood vessels
intensifies or persists, it can lead to small
hemorrhages due to bursting of some of the blood
capillaries.  Figure 8 (from Kant's 1933 article) is a
photograph showing the hemorrhagic damage in the
inferior colliculi and tissue surrounding the aqueduct.  
Figure 10, from Vortmeyer et al,1992 [15], shows
intense damage in the inferior colliculi caused by a
catastrophic and rapid depletion of thiamine in a
terminally ill patient maintained on intravenous
feeding.  Figure 16 (from Kant 1933) shows the more
intense damage in the mammillary bodies caused by
chronic alcohol intoxication.

Cerebellar involvement is also commonly observed as
part of Wernicke’s encephalopathy.  Cavanagh et al.
(1997) discussed an array of toxic substances that
deplete Purkinje cells and damage the cerebellar
vermis; these include L-beta-methylaminoalanine
(BMAA), penitrem A produced by Penicillium
crustosum, a fungus that contaminates food,
phencyclidine (PCP), and the plant-derived indole
terpenes ibogaine and harmaline [16].  The finding of
cerebellar involvement in children with autism, and of
autistic disorder in children exposed to alcohol and
other toxic substances during gestation is another
reason to consider degradation of function within the
brainstem nuclei of high metabolic rate as part of the
brain impairment in autism.
Figure 8
Figure 9
Figure 10
Figure 14
Figure 9 - Diagram showing brainstem sites affected in Wernicke's encephalopathy
Figure 8 - From Kant (1933).  Corpora quadrigeminae posterior, another name for
Figure 10 - From Vortmeyer et al. (1992)

Damage to the inferior colliculi
in a human patient maintained on
prolonged parenteral feeding
lacking vitamin B1
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Figure 14 - From Kant (1933), showing the usual site of most severe damage in
             Wernicke's encephalopathy, the mammillary bodies (corpus mamillare).
Full References
top
References
  1. Wernicke C (1881a) Die
    acute, haemorrhagische
    Poliencephalitis superior.
    Lehrbuch der
    Gehirnkrankheiten für Ärzte
    und Studirende,Band II.
  2. Brody IA, Wilkins RH. (1968)
    Wernicke's encephalopathy.
  3. Wernicke C (1874) The
    symptom complex of
    aphasia,.
  4. Gamper (1928) Zur Frage
    der Polioencephalitis
    haemorrhagica der
    chronischen Alkoholiker.  
    Anatomische Befunde beim
    alkoholischen Korsakow
    und ihre Beziehungen zum
    klinischen Bild.
  5. Kant F (1933) Die
    Pseudoencephalitis
    Wernicke der Alkoholiker.
    (polio-encephalitis
    haemorrhagica superior
    acuta).
  6. Malamud N,  Skillicorn SA
    (1956). Relationship
    between the Wernicke and
    the Korsakoff Syndrome.
  7. Torvik A (1987) Topographic
    distribution and severity of
    brain lesions in Wernicke's
    encephalopathy.
  8. Victor M, et al. (1989) The
    Wernicke-Korsakoff
    syndrome and related
    neurologic disorders due to
    alcoholism and
    malnutrition, 2nd ed,
  9. Butterworth RF (1993)
    Pathophysiology of
    cerebellar dysfunction in the
    Wernicke-Korsakoff
    syndrome.
  10. Franken L (1959) Étude
    anatomique d'un cas
    d'intoxication par le bromure
    de méthyle.
  11. 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.  
  12. Squier MV et al. (1992)
    Case report:
    neuropathology of methyl
    bromide intoxication.
  13. Hakim AM (1986) Effect of
    thiamine deficiency and its
    reversal on cerebral blood
    flow in the rat. Observations
    on the phenomena of
    hyperperfusion, "no reflow,"
    and delayed hypoperfusion.
  14. Chen Q et al. (1997)
    Causality of parenchymal
    and vascular changes in
    rats with experimental
    thiamine deficiency
    encephalopathy.
  15. Vortmeyer AO et al. (1992)
    Haemorrhagic thiamine
    deficient encephalopathy
    following prolonged
    parenteral nutrition.
  16. .Cavanagh JB et al. (1997)
    Selective damage to the
    cerebellar vermis in chronic
    alcoholism: a contribution
    from neurotoxicology to an
    old problem of selective
    vulnerability.
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the inferior colliculi
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  1. Wernicke C (1881a) Die acute, haemorrhagische Poliencephalitis
    superior. Lehrbuch der Gehirnkrankheiten für Ärzte und Studirende,Band
    II.  Kassel: Theodor Fischer, pp 229-242.
  2. Brody IA, Wilkins RH. (1968) Wernicke's encephalopathy. Archives of
    Neurology. 19:228-32.
  3. Wernicke C (1874) Der aphasische Symptomencomplex, Breslau: Franck
    und Weigert.  Translation: The symptom complex of aphasia, in Cohen
    RS & Wartofsky MW, eds (1969) Boston Studies in the Philosophy of
    Science, vol 4, pp 34-97.
  4. Gamper (1928) Zur Frage der Polioencephalitis haemorrhagica der
    chronischen Alkoholiker.  Anatomische Befunde beim alkoholischen
    Korsakow und ihre Beziehungen zum klinischen Bild. Deutsche Zeitschrift
    für Nervenheilkunde 102:122-129.
  5. Kant F (1933) Die Pseudoencephalitis Wernicke der Alkoholiker. (polio-
    encephalitis haemorrhagica superior acuta).  Archiv für Psychiatrie und
    Nervenkrankheiten 98:702-768.
  6. Malamud N,  Skillicorn SA (1956). Relationship between the Wernicke
    and the Korsakoff Syndrome.  Archives of Neurology and Psychiatry, 76,
    585-596.
  7. Torvik A (1987) Topographic distribution and severity of brain lesions in
    Wernicke's encephalopathy.  Clinical Neuropathology 6:25-29.
  8. Victor M, Adams RD, Collins GH (1989) The Wernicke-Korsakoff
    syndrome and related neurologic disorders due to alcoholism and
    malnutrition, 2nd ed, Contemporary Neurology Series v30. Philadelphia,
    PA : F.A. Davis Co.
  9. Butterworth RF (1993) Pathophysiology of cerebellar dysfunction in the
    Wernicke-Korsakoff syndrome. Canadian Journal of Neurological
    Sciences 20 Suppl 3:S123-S126.
  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. 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.
  12. Squier MV, Thompson J, Rajgopalan B. (1992) Case report:
    neuropathology of methyl bromide intoxication. Neuropathology and
    Applied Neurobiology 18: 579-584.
  13. Hakim AM (1986) Effect of thiamine deficiency and its reversal on
    cerebral blood flow in the rat. Observations on the phenomena of
    hyperperfusion, "no reflow," and delayed hypoperfusion. Journal of
    Cerebral Blood Flow and Metabolism 6:79-85.
  14. Chen Q, Okada S, Okeda R (1997) Causality of parenchymal and
    vascular changes in rats with experimental thiamine deficiency
    encephalopathy. Pathology International 47:748-756
  15. Vortmeyer AO, Hagel C, Laas R (1992) Haemorrhagic thiamine deficient
    encephalopathy following prolonged parenteral nutrition. Journal of
    Neurology, Neurosurgery and Psychiatry 55:826-829.
  16. .Cavanagh JB, Holton JL, Nolan CC (1997) Selective damage to the
    cerebellar vermis in chronic alcoholism: a contribution from
    neurotoxicology to an old problem of selective vulnerability.
    Neuropathology and Applied Neurobiology 23:355-363.