The topography of the neuropathologic changes in patients who die in the chronic stages of the disease, when the amnesic symptoms are established, is much the same as the changes in the acute stages of Wernicke disease. Apart from the expected differences in age of the glial and vascular reactions, the only important difference has to do with the involvement of the medial dorsal and anterior nuclei of the thalamus. The medial parts of these nuclei were consistently involved in the patients who had shown the Korsakoff amnesic state during life; they were not affected in patients who had had no persistent amnesic symptoms in the series of Victor et al (1989). The mammillary bodies were affected in all the patients, both those with the amnesic defect and those without. These observations suggest that the lesions responsible for the memory disorder are those of the thalami, predominantly of parts of the medial dorsal nuclei (and their connections with the medial frontal and temporal lobes and amygdaloid nuclei), and not those of the mammillary bodies, as is frequently stated. It is notable that the hippocampal formations, the site of damage in most other types of Korsakoff memory loss, are intact.
Treatment of the Wernicke-Korsakoff Syndrome
Wernicke disease constitutes a medical emergency; its recognition (or even the suspicion of its presence) requires the administration of thiamine. The prompt use of thiamine prevents progression of the disease and reverses those lesions that have not yet progressed to the point of fixed structural change. As emphasized earlier, in patients who show only ocular signs and ataxia, the administration of thiamine is crucial in preventing the development of an irreversible amnesic state.
Although 2 to 3 mg of thiamine may be sufficient to modify the ocular signs, particularly suppression of nystagmus, much larger doses are needed to sustain improvement and replenish the depleted thiamine stores—initially, 50 to 200 mg intravenously and a similar dose mg intramuscularly—the latter being repeated each day until the patient resumes a normal diet. Certain writings indicate that initial doses of 500 mg are necessary to fully reverse the manifestations of Wernicke disease and prevent progression to the point of a Korsakoff syndrome. It appears that these higher doses, given for several days parenterally, are needed to replete vitamin levels in alcoholic and nutritionally deprived patients (see the articles by Thomson et al and guidelines from the Royal College of Physicians). The risks of administering parenteral thiamine have probably been overstated; anaphylactic reactions occurred in 0.1 percent of the series of Wrenn and colleagues and minor reactions in 1 percent.
To avoid precipitating Wernicke disease, it has become standard practice in emergency departments to administer 100 mg or more of thiamine in malnourished or alcoholic patients if intravenous fluids that contain glucose are being infused. Magnesium is given as well because it is required as cofactor for thiamine activity. It is similarly advisable to give B vitamins to alcoholic patients who are seen for other reasons in the emergency department so as to raise body stores of thiamine and other vitamins. The patient with chronic alcoholism (or the nonalcoholic patient with persistent vomiting) exhausts thiamine in a matter of 7 or 8 weeks, during which time the administration of glucose may serve to precipitate Wernicke disease or cause an early form of the disease to progress rapidly. The further management of Wernicke disease involves the use of a balanced diet and all the B vitamins, as the patient is usually deficient in more than thiamine alone.