Journal of Neurology Research Reviews & Reports

Introduction

Marchiafava–Bignami Disease (MBD) was first reported in 1903 in Italy by Ettore Marchiafava and Amico Bignami [1]. MBD is a chronic disease that is distinguished by demyelination and necrosis in the corpus callosum. It is common in patients who abuse alcohol and is thought to stem from a vitamin B1 deficiency [2]. The mean age of onset is 45 years. MBD has a higher reported incidence in males possibly due to higher alcohol consumption compared to females [3]. MBD prevalence is low, with only about 250 cases reported between 1903 and 2001 [4].

The pathogenesis of MBD is related to ethanol and vitamin B1 deficiency. Ethanol causes hypovitaminosis (mainly vitamin B1) and generation of free radicals in the central nervous system that directly damage the corpus callosum with consequent demyelination and necrosis. Vitamin B1 is a critical cofactor for multiple enzymes involved in carbohydrates metabolism. Deficiency of vitamin B1 compromises carbohydrates metabolism in the brain leading to neurological impairment [3]. Symptoms of MBD include seizures, neurocognitive deficits, and in the most severe cases, a comatose state or death. (Figure 1) While MBD patients typically have a poor prognosis, some recover when provided with a vitamin B1 supplement [2]. (Figure 2)

Literature regarding MBD is very limited. To date, MBD with concomitant deep vein thrombosis (DVT) has never been documented. We herein present the first documented case of a 52-year-old-male with diagnosis of MBD and concurrent bilateral DVT.

Case Report

RR is a wheelchair-bound 52-year-old male with a current medical history of alcohol abuse, tobacco abuse, and failure to thrive. He was diagnosed with Marchiafava-Bignami Disease five years ago. At the time of diagnosis, he was in a comatose state for ten days and received a percutaneous endoscopic gastrostomy (PEG) tube and tracheostomy tube. The tubes were removed after the patient regained consciousness. He was brought to the emergency room (ER) with a complaint of bilateral leg swelling and pain for three days. No reported fever, headaches, loss of vision, chest pain, shortness of breath, abdominal pain, change in bowel movement, focal neurological weakness, or sensory loss. In the ER, a doppler venous ultrasound revealed occlusive thrombus limited to the common femoral vein on the right lower extremity. Contrastingly, the thrombus affected the entire femoral-popliteal venous system on the left lower extremity. Per admission, the temperature was 98.2 F, pulse 79 beats/min, respiratory rate 18 breaths/min, blood pressure 122/82, oxygen saturation 100% on room air.

On physical examination, the patient appeared chronically ill- appearing, frail, malnourished and looked older than the stated age. Bilateral lower extremities exhibited swelling, warmth, and decreased range of motion. Neurological examination displayed no motor or sensory deficits. Pupils were equal, round, and reactive to light bilaterally. Complete blood count and comprehensive metabolic panel were significant for macrocytic anemia, elevated aspartate transaminase (AST), and alkaline phosphatase with normal alanine transaminase (ALT). COVID-19 rapid test was negative.

The patient started on an intravenous therapeutic dose of anticoagulant which was later switched to oral anticoagulant per hematology recommendation. The patient was hemodynamically stable and was discharged home three days after admission with a plan to follow up with a hematologist. MBD has not been resolved and associated symptomatology continues to persist in the patient.

Figure 1: Overview of Marchiafava-Bignami Disease CC = Corpus callosum

Figure 2: Prognosis of Marchiafava-Bignami Disease

The prognosis of MBD is variable. Some patients may be symptomatic and survive for years, recover fully, or die from end-organ damage.

Figure 3: Axial images of brain MRI

1. T1-weighted imaging demonstrating hypointensity of the genu (white arrow) and the splenium (white arrowhead) of corpus
2. T2-weighted imaging showing hyperintensity of the genu (white arrow) and the splenium (white arrowhead) of corpus

The following original report is credited [5]:

Discussion

Marchiafava-Bignami Disease is a rare neurological complication of alcoholism characterized by targeted demyelination of the corpus callosum [6]. However, several cases of MBD have been reported in patients with poorly controlled diabetes mellitus without a history of alcohol abuse [7-9]. The precise pathomechanism of MBD remains unknown. It is postulated that the toxic effects of alcohol and vitamin B deficiency are major contributors to the necrosis and demyelination of the corpus callosum [3]. Our patient’s long history of alcohol abuse and secondary nutritional deficiencies likely contributed to the pathogenesis of the disease.

Marchiafava-Bignami Disease is classified into two subtypes, according to clinical status and neuroradiological findings: [3]

1. Type A presents with acute or subacute clinical findings which may include altered level of consciousness, cognitive deterioration, dysarthria, aphasia, hypertonia, seizures, hemiparesis, Neuroradiologically, Type A typically is characterized by extracallosal lesions with swelling of the entire corpus callosum. Type A is typically associated with a poor prognosis. The patient’s history and presentation fit the diagnostic criteria of Type A MBD.
2. Type B is a milder form than Type A. Type B manifests as a progressive and insidious onset of MBD. Patients commonly present with normal or slightly impaired levels of consciousness, gait abnormalities, and dysarthria. Compared to Type A, MRI findings in Type B reveal partial involvement of the corpus callosum, sparing the extracallosal regions in most Likewise, Type B has a favorable prognosis.

Diagnosing patients with MBD based on clinical presentation may be challenging for providers. Clinical symptoms associated with Type A and Type B MBD are non-specific and may manifest in other alcohol-related conditions such as alcohol withdrawal

syndrome, Wernicke’s encephalopathy, and delirium. Furthermore, dementia, epilepsy, encephalitis, and vascular disturbances may also present with symptoms seen in Type A and Type B MBD [10- 12]. Therefore, radio neurological imaging must be implemented to confirm MBD diagnosis. Characteristic MRI findings of the brain in patients with MBD consist of T1 hypointensity and T2 hyperintensity involving the central portion of the corpus callosum with possible extension to the genu and splenium. (Figure 3)

Currently, no management guidelines exist for the treatment of MBD. However, several case reports have shown clinical improvement with high-dose thiamine and vitamin B complex supplementation [12, 13]. Additionally, high-dose corticosteroids and amantadine have demonstrated favorable outcomes [14]. We recommend that patients with a severe history of alcohol abuse consider enrollment in alcohol rehabilitation programs and ensure optimal nutrition. Periodic blood level testing of thiamine and other B vitamins may help identify individuals at highest risk for the development of MBD. Anticoagulation therapy may be indicated as a prophylactic measure for immobile patients.

Conclusion

In conclusion, we present a novel case of MBD with concomitant DVT. Such a case has yet to be reported in the scientific literature. This case report underscores the clinical significance of DVT as a potential long-term complication of MBD. Additional research is needed to establish an association between MBD and DVT development. Furthermore, management guidelines for patients with MBD are recommended to improve mortality rate, prognosis, and quality of care.

Acknowledgment

This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.

References

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