91.1 Clinical Features
and Laboratory Investigations Marchiafava–Bignami syndrome (MBS) is a disorder characterized by primary degeneration of the corpus callosum in chronic alcoholics. Although a high pro- portion of reported cases have been Italians, drinking Italian wine, the condition has also been described in many non-Italians drinking non-Italian wine. Most affected cases were middle-aged men whose daily wine consumption had been 2 l or more for many years.
The disease has three major clinical forms: acute, subacute, and chronic. The acute form is character- ized by sudden onset with severe disturbances of con- sciousness, sometimes heralded by convulsions. The initial phase is followed by the development of persis- tent coma or stupor with pyramidal signs and hyper- tonia. Patients are generally mute, but if they say a few words, they appear to be severely dysarthric. They may die within a few days. The subacute condition is characterized by rapidly progressive dementia, some- times following an initial acute state with temporary coma or convulsions. The dementia has characteris- tics of a split-brain syndrome. The patients are usual- ly dysarthric. Hypertonia of the limbs is quite com- mon and marked by strong opposition to any move- ment, either flexion or extension. There is spastic flex- ion of the arms and extension of the legs with hyperreflexia and extensor plantar reflexes. A facial grimace and trismus may be present, as well as opisthotonus. In the end stage the patients are unable to walk or stand. Severe dementia usually progresses to a vegetative state and death within a few months. In the chronic form, which is much less common, de- mentia progresses slowly over a number of years.
Neurological examination reveals diffuse rigidity, dysarthria, and inability to stand or walk, as in the subacute form. This condition progresses steadily to- wards death several years later. It should be noted, however, that in a few cases improvement of the pa- tient’s condition and disappearance of image abnor- malities have been reported.
Laboratory investigations may reveal vitamin defi- ciencies due to malnutrition but they are probably not directly related to MBS. Combinations of Wernicke encephalopathy with MBS have been described. There is no laboratory test for MBS.
91.2 Pathology
The principal pathological change is necrosis of the corpus callosum. The necrosis may involve the entire length of the corpus callosum or only a part of it. The middle layers of the splenium and genu are mainly af- fected, an upper and lower rim of the callosal fibers usually being preserved. The lesion extends laterally to the edges of the corpus callosum. When necrosis is incomplete, demyelination is found, with relative preservation of axons and a moderate glial reaction.
In cases of total necrosis, both myelin and axons have disappeared and are replaced by an accumulation of macrophages and perivascular cells together with a variable glial reaction. The lesion is sharply delineat- ed. In acute cases the lesion appears in the form of a band of edematous necrosis with fresh coagulation.
An upper and a lower band of normal callosal tissue remains. In cases of long duration, the corpus callo- sum is thinned and atrophic with a slit or band of de- myelination in the middle, most conspicuous in genu and splenium. Macrophages accumulate in perivascu- lar areas.
Other regions of white matter are sometimes in- volved, including the centrum semiovale in the frontal, parietal, and occipital region as an extension of the lesion of the corpus callosum. Sometimes the lesion includes all the white matter up to the U fibers.
Furthermore, the cerebellar peduncles and the anteri- or commissure may be affected. The fornix is thought never to be affected. Also, these lesions are primarily characterized by demyelination with accumulation of macrophages. In complete necrosis axons are also lost. The ventricles are moderately enlarged, and in most cases there is some cortical atrophy. There is oc- casionally cortical laminar necrosis and, exceptional- ly, necrosis of the basal ganglia.
91.3 Pathogenetic Considerations
The pathogenesis of MBS is still unknown. A toxic factor present in cheap red wine seems to be the clos- est constant association, but the factor responsible has never been identified. It has been shown that vit- amin deficiencies are not important in the pathogen- esis, as a supply of vitamins does not prevent MBS in animals. There are, however, a few descriptions of the
Marchiafava–Bignami Syndrome
Chapter 91
091_Valk_Marchiafava_Big 08.04.2005 16:49 Uhr Seite 695
combination of MBS with Wernicke encephalopathy.
Lesions of the white matter affecting the corpus callo- sum and anterior commissure have been described following chronic cyanide intoxication and chronic methyl alcohol intoxication. However, the patho- genetic similarities on the molecular level between MBS and these intoxications are unclear. Why the central layers of genu and splenium of the corpus cal- losum are preferentially affected in MBS remains ob- scure. The cause of the additional gray matter lesions, usually in the form of laminar necrosis of the cerebral cortex, has not been explained satisfactorily. The most attractive hypothesis would seem to be that the cortical necrosis is secondary to the callosal lesion, which leads to loss of neurons due to secondary de- generation.
91.4 Therapy
There is no effective treatment for MBS; only sympto- matic treatment is possible. However, it is important not to overlook other complications of long-standing alcoholism, particularly vitamin deficiencies and dis- turbances of electrolytes.
91.5 Magnetic Resonance Imaging
CT scan may show abnormality of the corpus callo- sum with some swelling and edema in the acute form.
The corpus callosum lesions in the subacute or chron- ic forms of the disease, which are not associated with swelling, may be more difficult to detect on CT. Ex- tensive hypodense areas may be found in the cerebral hemispheric white matter. Contrast enhancement
has been described in the early stages of the disease.
In the later stages there is atrophy of the corpus callosum, progressive and marked widening of the cerebral sulci, and dilatation of the lateral ventri- cles.
The corpus callosum lesions are much more easily visualized by MRI (Figs. 91.1 and 91.2). The sagittal MR images are diagnostic: they show the typical pat- tern of the corpus callosum splitting into three layers, with relative sparing of the upper and lower layers. In the initial stages of the disease the corpus callosum appears swollen and contrast enhancement may be present, in particular in the genu and splenium. Cal- losal hemorrhage may occur in the subacute stage.
The middle layer may become cystic in the later stages of the disease and the corpus callosum be- comes atrophic. Cerebral hemispheric white matter may be involved, with a less characteristic appear-
Chapter 91 Marchiafava–Bignami Syndrome 696
Fig. 91.1. A 53-year-old man with MBS with acute onset. MRI on the ninth day (left image) shows contrast-enhancing lesions in the genu and the splenium of the corpus callosum. At 3 weeks the images (middle and right images) show involvement
of the middle layer of the corpus callosum, in particular in sple- nium and genu, but no contrast enhancement. The splenium and genu show cystic degeneration. From Caparros-Lefebvre et al. (1994), with permission
Fig. 91.2. A 56-year-old man with MBS. The first and second rows of images were obtained in the acute phase. The sagittal T
2-weighted images (first row) show that especially the middle layer of the corpus callosum is involved.The axial FLAIR images (second row) show the predominant involvement of the corpus callosum with some additional lesions in the deep periventricular white matter. A follow-up MRI was obtained 50 days later (third and fourth rows). The sagittal T
1-weighted images (third row) show cavitation of the middle layer of the genu and splenium of the corpus callosum. The hyperintense lesions on the axial T
2-weighted images (fourth row) are less conspicuous. From Yamamoto et al. (2000), with permission
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