MBD is a rare acute to chronic disorder that most frequently occurs in chronic alcoholics, followed by malnourished people. In terms of its pathophysiology, MBD can be attributed to the direct and indirect toxic effects derived from chronic alcohol consumption as well as malnutrition. Drinkers generally eat less food, and furthermore, alcohol-induced gastrointestinal injury inhibits the absorption of multiple vitamins, like B-vitamins. Of the B-vitamins, B1 plays an important role in human body in the form of pyrophosphate thiamine (TPP). TPP is an important coenzyme of glycolysis pathway and pentose phosphate pathway, which contributes to the energy supply and phospholipid metabolism of nerve tissue. Deficiency of TPP affects the function of nerve tissue and leads to demyelination and axon loss of the nerve tissue. In addition, deficiency of vitamin B1 can also increase the activity of cholinesterase and accelerate the hydrolysis of acetylcholine (ACh), which can affect the normal conduction of impulses in nerve tissue. The latter can decrease the liver’s ability to clear toxic metabolites in the blood, which can further increase oxidative stress and neurotoxicity .An emerging mechanism of direct neurologic injury suggests that the metabolites of ethanol accumulate to disrupt function of lipid, mitochondrial,endoplasmic reticulum and so on. This can cause strong oxidative stress accompanied by production of stress-response proteins and reactive oxygen species as well as activation of intracellular signal cascade reactions to initiate neuronal cell death. Simultaneously, ethanol can also directly decrease the production of brain-derived neurotrophic factor, promoting neuronal cell growth and differentiation, and thus leading to the death of neurons. Chronic alcohol use may cause disorders of neurotransmitters, including dopamine, GABA, glutamate, noradrenaline, opioids and serotonin. For instance, ethanol can suppress the NMDA receptor and thus reduce the excitatory effects of glutamate. The indirect effects of alcohol consumption arise from thiamine deficiencies and hepatic dysfunction. The former can lead to disorders in synthesis and metabolism of substances that are essential to neurogenesis[1,3].
The corpus callosum is a fiber-rich white matter tract that connects left and right cerebral hemisphere and has a relatively high myelin content. The corpus callosum, especially the splenium, is vulnerable to a variety of external and internal risk factors, like alcoholic toxicity and thiamine deficiency.Neurologic defects are mild when the corpus callosum lesions are small or the sites involved are few. On the contrary, when the corpus callosum lesions are diffuse or involved in multiple sites, the neurologic defects are very serious . Meanwhile, there are also many other sites which have been described and can be involved (mentioned above)[3,8,9].So the clinical manifestations of MBD are diverse and unspecific and thus, difficult to diagnosis.
This study describes a patient diagnosed two years previously with erosive gastritis and had a 40-year history of heavy alcohol abuse. Considering the above risk factors, we infer that the serum level of vitamin B1 was decreased. Thus, it can be speculate that the patient’s MBD may be closely associated with chronic alcoholism and/or malnutrition, and especially B-vitamins (Mainly vitamin B1, Thiamine)deficiencies.
There are three types of MBD: (1) acute MBD, which is characterized by severe disturbance of consciousness, such as coma and dizziness, which may be accompanied by increased muscular tension, disorientation,seizure, dysarthria, and frontal lobe symptoms; (2) subacute MBD, which is characterized by a rapid progression of dementia, inability to stand and walk, behavioral abnormalities, apathy, visual hallucinations, and likely progressing into chronic disease. (3) chronic MBD, which is characterized by progressive dementia, behavioral abnormalities, disturbance of intelligence, and interhemispheric disconnection syndrome[7,11]. Whereas the above mentioned clinical classification of Brion et al is still widely used, Heinrich et al proposed a clinicoradiologic classification.Considering the patients’ clinical status as well as the radiological severity of cerebral changes detectable on MRI, it was recommended that the disease could be classified as type A and type B. Type A is characterized by alterations of consciousness and diffuse swelling of the entire corpus callosum on imaging. Type B is characterized by mild impairment of consciousness and small callosal lesions associated with good prognosis. According to clinicoradiologic manifestations, most MBD cases can be assigned to one of these two groups.
The patient in this case study can be classified as type A from a clinicoradiologic point of view (acute onset with suspected expressive aphasia, alterations of mental status, pyramidal tract syndromes and the strong affection of the complete corpus callosum). Type A has a worse prognosis . Considering his short medical history and clinical manifestations, the patient was likely in the acute stage.
The role of MRI is essential in making the diagnosis, differentiating the different subtypes,identifying degree of involvement, and predicting prognosis in vivo. Conventional MRI in MBD typically detects lesion areas of low T1 signal intensity and high T2 signal intensity as well as FLAIR and DWI in the body of the corpus callosum, followed by the genu and the splenium. However, the entire corpus callosum is rarely involved [7,13]. Degeneration of the corpus callosum mainly involves the middle layer rather than the upper and lower margins. The best method to assess callosal lesions is sagittal MRI which offers the ability to visualize the entire corpus callosum. By contrast, accurate visualization of the body of the corpus callosum is difficult in the axial planes, limiting the diagnostic yield of axial MRI and particularly CT. In sagittal MRI, like T1WI and T2WI, we observe that MRI of MBD are characterized by symmetrical lesions of the corpus callosum situated in the central layer sparing the dorsal and ventral layers, resulting in a sandwich-like appearance(Figure2). As mentioned earlier, the DWI,which displays a limited extent of diffusion,is sensitive to cytotoxic edema. During the acute phase, the involved regions become oedematous. Reduced diffusion and hyperintensity are often seen on DWI with decreased values on ADC mapping.
The MRI of the patient in the present case was quite typical, and consistent with those expected for MBD. Although MRI revealed hyperintensity on T2WI and FLAIR in the entirety of corpus callosum and corona radiata (Figure1 a, b, c, d), only the corpus callosum appearedto be hyperintense on DWI (Figure1 e, f). A possible explanation for this phenomenon is that the corona radiate lesion was mild and insufficient to limit diffusion. It may also be that the damage in the corona radiate was an obsolete cerebral injury. That is to say, the callosal lesion was the main reason for this hospitalization.
The diagnosis of MBD is based on the callosal lesions. Differentiation of MBD from infarction of the corpus callosum may be difficult. However, selective involvement of the entire length of the corpus callosum without significant mass effect and focal cystic necrosis confined to its central layer are more likely to be attributed to MBD. Many other diseases that involve the corpus callosum like paraneoplastic syndrome (PNS), multiple sclerosis (MS),Wernicke’s encephalopathy (WE) and so on had to be excluded based on the clinical manifestations, laboratory findings and imaging features prior to a diagnosis of MBD. The combination of chronic alcoholism, clinical features, laboratory tests and MRI findings (showing the detailed parts involved in the diseases) were used to exclude those diseases and support the correct diagnosis.
After treatment with vitamin B complex (vitamin B 1, B 6, B 9, and B 12), the patient’s symptoms did not relieve significantly. Reviewing his treatment process, it was speculated that this might be due to the mode of administration (stomach tube) and dosage (60mg/d) of vitamin B1 (personal opinion). In addition, poor prognosis may be related to the brain areas involved in the MBD. It is still controversial whether the appearance of extra-callosal lesions, like in the cerebral cortex, subcortical white matter or corona radiate etc., can be used to predict a poorer prognosis[6,18]. A review by Heinrich and Menegon stated that involvement of the entire callosum and of the cortex were poor prognostic factors[6,7]. When the entire corpus callosum is involved, the function of the corpus callosum cannot be compensated(personal opinion), which may explain the poor prognosis of our patient. Although there is no conclusive evidence, we speculate that corona radiate injury is also involved in the poor prognosis. Otherwise, Ménégon P et al reported that cytotoxic edema on DWI and the ADC map might also predict poor outcome. All in all, the risk factors that could potentially lead to poor prognosis were prevalent in our patient, likely explaining his poor prognosis.
MBD should be considered in the evaluation of alcoholic or malnourished patients who present acute, subacute or chronic neurological symptoms. MRI findings, especially the DWI sequence, are critical for the diagnosis of MBD. Early diagnosis and treatment may prevent irreversible corpus callosum damage. What we must keep in mind is that prevention is the key to disease. So we should pay attention to health education in order to maximize the prevention of disease.