weresearch4txt

4 - A hundred years of evidence
Brody and Wilkins (1968) published an English
translation of part of Wernicke's original paper. Many
reports in German appeared in the first decades of
the twentieth century confirming Wernicke's
observations. Even for a decade or two after the
Second World War a reading knowledge of German
was thought as essential as English is today for full
access to scientific communications, and to learn
French was part of intellectual development for
anyone with scholarly interests. Decreasing
emphasis on learning foreign languages in the United
States leaves much of the scientific literature from the
early twentieth century unavailable to English-
speaking researchers of today.

Not only are the data still valid, but the ideas of
people like Gamper (1928), Kant (1933), and
Neubürger (1991, 1937) are still worth consideration.
Translation and discussion of these and many more
reports would be a worthwhile project.

Gamper (1928) investigated the brains of 16 chronic
alcoholics; all were also cases in which death
occurred within two weeks of acute intoxication. He
described hyperemia and small fleabite size
hemorrhages were evident in some cases but not all.
Gamper emphasized his frequent finding of
surprisingly severe damage in the inferior colliculi.
Gamper also cited reports on overdoses of sleep-aid
medications and morphine that produced the same
pathology and suggested that alcohol was just one of
a group of toxic substances that cause this pattern of
damage in the brain.

As for the predilection sites Gamper concluded that
damage of the mammillary bodies was the most
constant feature, and responsible for the psychic
disorder and memory deficits described by Korsakoff
(1889, translated by Victor & Yakovlev 1955). Victor
et al. (1989) discussed the historical background that
lead to differentiating between the Wernicke and
Korsakoff syndromes. Korsakoff’s clinical
descriptions included the same kinds of delerium and
psychosis discussed by Wernicke (1881), but
Korsakoff disease has come to refer to patients who
have difficulty incorporating recent events into long-
term memory.

Short-term and long-term memory are intact in the
core syndrome of Kanner autism, and memory
remains intact throughout the lifespan. Thus the
limbic system would appear to be less involved than
the auditory system in most cases of autism.
Variability is common in clear-cut cases of Wernicke's
encephalopathy; hence a Wernicke-like involvement
of brainstem nuclei in autism should not have to fit
narrow requirements of what is or is not a true
Wernicke encephalopathy.

Kant (1933) reported clinical and autopsy findings in
17 more cases of chronic alcohol use, and he
reviewed the literature to date, 50 years after
Wernicke's original report. Figures 11 and 16 are
photos from Kant's article (reproduced here with
permission from Springer Verlag). Figure 11 is still
an excellent example of the petechial (flea-bite size)
hemorrhagic damage first reported by Gayet and
Wernicke. Like Gamper, Kant found the mammillary
bodies most seriously damaged, but also noted the
important and consistent involvement of the inferior
colliculi.

Malamud and Skillicorn (1956) examined the brains of
70 institutionalized patients with mental deterioration,
of whom 63 had been chronic alcoholics. The other
seven patients had severe nutritional deficiencies,
four due to gastrointestinal carcinoma. All had the
memory impairment characteristic of Korsakoff
syndrome. They found no acute hemorrhagic lesions
but did find degenerative changes in the areas
affected in Wernicke’s disease. In one brain
inflammatory changes were found in the mammillary
bodies, thalamus, and oculomotor nuclei
superimposed upon a more chronic overgrowth of
glial cells (gliosis). Glial cells proliferate around
compromised neurons, and may supply extra
nutrients such as glucose that could prevent death of
a neuron, though often glial scars are all that remain
at a site of injury.

Of the 70 brains they examined Malamud and
Skillicorn (1956) found damage of tissue around the
ventricles in every case, and lesions of the
mammillary bodies in all but three. Nuclei of the
thalamus were damaged in 37 cases and the
cerebellum in 24. Symmetric lesions of brainstem
nuclei were observed in 16 cases including the
inferior olives in 5, vestibular nuclei in 5, inferior
colliculi in 4, and oculomotor nuclei in 2. Based on
the distribution of the lesions in these long-standing
cases in which the short-to-long-term memory deficit
of Korsakoff disease had been evident, Malamud and
Skillicorn concluded that Wernicke’s encephalopathy
and Korsakoff syndrome represented acute and
chronic forms of the same disorder.

Torvik (1987) distinguished between 11 acute and 10
chronic cases in 21 patients for whom sections
through the brainstem were available. He found the
mammillary bodies damaged in every case, and his
criterion for diagnosis of acute disease was presence
of swollen capillary endothelium in the mammillary
bodies, i.e. evidence that death occurred during a
period of active vascular response. More lesions
were evident in the acute cases, and those in the
chronic cases were described as scars. Damage of
the inferior colliculi was found in all but one of the
acute cases.

Torvik found lesions of the thalamus in 10 of the
acute and 6 of the chronic cases, and of the inferior
colliculus in 10 of the acute and 2 of the chronic
cases. The inferior olives were damaged in 4 of the
acute and 1 of the chronic cases. Damage within the
dorsal pons and dorsal medulla was found in 8 and 5
acute cases respectively. Torvik described the
predominant symptoms in acute cases to have been
drowsiness and coma. Chronic cases had mild to
severe memory loss. Torvik noted atrophy of the
anterior vermis of the cerebellum in about one third of
the brains he examined.

Lesions of the mammillary bodies and inferior colliculi
can now be detected in magnetic resonance imaging
(MRI) scans (D’Aprile et al. 1994). In addition to
brainstem sites, the cerebellum is commonly involved
(Butterworth 1993, Cavanagh et al. 1997), and is
viewed as responsible for the ataxic unsteady gait of
alcoholics.

Brody IA, Wilkins RH. (1968)
Wernicke's encephalopathy.
Gamper (1928) Zur Frage der
Polioencephalitis
haemorrhagica der
chronischen Alkoholiker.
Anatomische Befunde beim
alkoholischen Korsakow und
ihre Beziehungen zum
klinischen Bild.
Kant F (1933) Die
Pseudoencephalitis Wernicke
der Alkoholiker. (polio-
encephalitis haemorrhagica
superior acuta).
Neubürger K (1931) Über
Hirnveränderungen nach
Alkoholmissbrauch.
Neubürger K (1937)
Wernickesche Krankheit bei
chronischer Gastritis. Ein
Beitrag zu den Beziehungen
zwischen Magen und Gehirn.
Korsakoff SS (1889) Psychic
disorder in conjunction with
multiple neuritis.
Victor M et al. (1989) The
Wernicke-Korsakoff syndrome
and related neurologic
disorders due to alcoholism
and malnutrition, 2nd ed.
Wernicke C (1881) Die acute,
haemorrhagische
Poliencephalitis superior..
Malamud N, Skillicorn SA
(1956). Relationship between
the Wernicke and the Korsakoff
Syndrome.
Torvik A (1987) Topographic
distribution and severity of
brain lesions in Wernicke's
encephalopathy.
D'Aprile P et al. (1994)
Enhanced MR in the acute
phase of Wernicke
encephalopathy.
Butterworth RF (1993)
Pathophysiology of cerebellar
dysfunction in the Wernicke-
Korsakoff syndrome.
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.

Brody IA, Wilkins RH. (1968) Wernicke's encephalopathy. Archives of Neurology. 19:228-32.
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
Kant F (1933) Die Pseudoencephalitis Wernicke der Alkoholiker. (polio-encephalitis
haemorrhagica superior acuta). Archiv für Psychiatrie und Nervenkrankheiten 98:702-768.
Neubürger K (1931) Über Hirnveränderungen nach Alkoholmissbrauch. Zeitschrift für die
gesamte Neurologie und Psychiatrie 135:159-209.
Neubürger K (1937) Wernickesche Krankheit bei chronischer Gastritis. Ein Beitrag zu den
Beziehungen zwischen Magen und Gehirn. Zeitschrift für die gesamte Neurologie und
Psychiatrie 160:208-225.
Korsakoff SS (1889) Psychic disorder in conjunction with multiple neuritis. Translated by
Victor M & Yakovlev PI (1955) Korsakoff's psychic disorder in conjunction with peripheral
neuritis: a translation of Korsakoff's original article with brief comments on the author and his
contribution to clinical medicine, Neurology 5:394-405
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.
Wernicke C (1881a) Die acute, haemorrhagische Poliencephalitis superior. Lehrbuch der
Gehirnkrankheiten für Ärzte und Studirende,Band II. Kassel: Theodor Fischer, pp 229-242.
Malamud N, Skillicorn SA (1956). Relationship between the Wernicke and the Korsakoff
Syndrome. Archives of Neurology and Psychiatry, 76, 585-596.
Torvik A (1987) Topographic distribution and severity of brain lesions in Wernicke's
encephalopathy. Clinical Neuropathology 6:25-29.
D'Aprile P, Gentile MA, Carella A (1994) Enhanced MR in the acute phase of Wernicke
encephalopathy. AJNR. American Journal Of Neuroradiology 15:591-593.
Butterworth RF (1993) Pathophysiology of cerebellar dysfunction in the Wernicke-Korsakoff
syndrome. Canadian Journal of Neurological Sciences 20 Suppl 3:S123-S126.
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