Marchiafava-Bignami disease presenting as reversible coma
- 1 Internal Medicine, University of Florida College of Medicine - Jacksonville, Jacksonville, Florida, USA
- 2 Neurology, UF Health Jacksonville, Jacksonville, Florida, USA
- Correspondence to Dr Yixin Zhang; wendyz0411@gmail.com
Abstract
Marchiafava-Bignami disease (MBD) is a rare demyelinating condition of the corpus callosum and subcortical white matter that is most commonly seen in alcoholic patients. The course of the disease varies with symptoms that range from dementia to complete coma; severe intermittent sympathetic storming with abnormal posturing is often reported in literature. It is presumably secondary to a deficiency of B complex vitamins, specifically thiamine and many patients have clinical improvement after repletion of B vitamins. We present a case of a 35-year-old man who developed MBD secondary to polysubstance misuse without history of alcohol use. His clinical course was complicated by persistent comatose state with autonomic dysfunction. After the administration of high-dose thiamine and vitamin C and E, the patient regained consciousness and was able to follow commands within 48 hours. Furthermore, this case showed recognising brain MRI findings for MBD is a crucial step in disease identification.
Background
Marchiafava-Bignami disease (MBD) causes demyelination and necrosis of the corpus callosum and subcortical white matter.1 The exact aetiology remains unclear as there have only been a handful of cases reported in the literature. It is presumably secondary to direct neurotoxic insult and B complex vitamin deficiency, as it is commonly diagnosed in malnourished patients with alcohol use disorder.2 Brain imaging may reveal lesions in the cerebral lobes, hemispheric white matter and basal ganglia. However, it can be differentiated from other encephalopathies by its pathognomonic findings of high signal intensity in the corpus callosum on diffusion-weighted imaging and fluid-attenuated inversion recovery (DWI-FLAIR) images.1
MBD has also been seen in non-alcoholic patients, suggesting other unidentified causes. In this case, we present a 35-year-old man with characteristic imaging findings of MBD on MRI of the brain after being found unconscious. This case is also unique because there have been few reported cases of MBD treated with a combination of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), in addition to the commonly used B complex vitamins.
Case presentation
A man in his 30’s with a history of polysubstance misuse was presented to the emergency department (ED) in an unconscious state after being found down on the street. On initial physical exam, he had a Glasgow Coma Scale score of 4, febrile reaching 103oF, hypertensive and hyper-reflexic. Blood work obtained showed sodium 143 mmol/L, potassium 5.1 mmol/L, creatinine 1.23 mg/dL, total creatine kinase 477 U/L, white blood cell count 23.18 x 10ˆ9/L, haemoglobin 181g/L and platelet count 293 x 10ˆ9/L. Urine toxicology was positive for cocaine and amphetamine. Serum alcohol levels were undetectable. Serum vitamin B12 level was 397 pg/mL. He was intubated and admitted to the intensive care unit (ICU). Further history obtained from the family and friends confirmed that the patient does not drink alcohol on a regular basis but has a history of extensive polysubstance misuse. After 8 days of ICU admission, the patient remained unconscious with periodic agitation despite minimal sedatives. Furthermore, the patient developed intermittent decerebrate posturing, hypertension, tachycardia and spasticity.
Investigations
Electroencephalography showed severe encephalopathy without epileptic waveforms. Lumbar puncture with CSF analysis showed normal opening pressure, elevated glucose level of 108 mg/dL, normal protein level of 18 mg/dL and 0 white blood cell count. CT of the head without contrast showed hypodensities in the genu and splenium of the corpus callosum. Brain MRI with and without contrast revealed restricted diffusion in the periventricular region, parieto-occipital lobe (figure 1) and splenium of the corpus callosum (figure 2A–C). No lesions were seen in the hypothalamus (figure 2D) or brain stem (figure 2E,F) where reticular activating system (RAS) and its primary structure resides, which indicates patient’s unconscious state is not due to RAS injury. These image findings along with neurological findings on physical examination were consistent with MBD.
Restricted diffusion in the parieto-occipital lobes (left, red arrows), comparing to T2-FLAIR image (right).
(A) Axial view of diffusion-weighted imaging (DWI) with hyperintensity, indicating diffusion restriction. (B) Axial view of apparent diffusion coefficient sequence with hypointensity, indicating diffusion restriction. (C) Axial view of T2- FLAIR axial which does not show any chronic cytotoxic or vasogenic oedema. (D) Axial view of intact hypothalamus (red arrow). (E,F) Axial views of both DWI and T2-FLAIR view of the pons, no acute lesions are seen.
Treatment
After diagnosing him with MBD based on MRI imaging, the patient was treated with a combination of 500 mg intravenous thiamine every 8 hours, 1 mg of intravenous folic acid daily, 1000 mg oral vitamin C and 400 units of vitamin E daily.
Outcome and follow-up
The patient’s mental status improved within 48 hours of combination vitamin therapy and his decerebrate posturing was also diminished. He was then discharged to short term rehab for physical therapy and further strength training for 2 weeks. Unfortunately, we were unable to obtain a repeat MRI as the patient was lost to follow-up
Discussion
MBD is a central nervous system disorder that is characterised by demyelination and eventual necrosis of the corpus callosum which contains approximately 200 million extensively myelinated nerve fibres connecting two brain hemispheres.1 3 It was first seen in alcoholic patients in the early 1900s.1 One hypothesis is that MBD can be attributed to a deficiency of B complex vitamins and many patients improve after repletion of B vitamins.4 MBD can be classified into two types based on clinical severity.1 Patients with type A MBD typically have profound loss of consciousness, seizures and dysarthria. Hyperintensity of the entire corpus callosum can be seen on MRI in type A MBD.1 4 Type B MBD is associated with milder impairment in consciousness, gait disturbances and only a partial callosal lesion is identified on MRI.1 4 MBD can also be classified based on symptom onset.5 Acute symptoms of MBD include severe altered mental status, seizures and limb hypertonia.5 Subacute symptoms of MBD include confusion, dysarthria, behavioural abnormalities, somnolence and visual disturbances.5
Our patient was initially brought to the ED with acute encephalopathy. During his admission, he was noted to have episodic extensor posturing along with tachycardia, hypertension, hyperthermia, diaphoresis and spasticity, a phenomenon known as paroxysmal sympathetic hyperactivity, or PSH.6 PSH is frequently observed in patients with post-traumatic brain injury and severe white matter inflammation/insult in non-traumatic patients; it is also worth noting that those with deeper brain structure damage such as the corpus collasum or periventricular white matter are more likely to develop PSH than those with cortical or subcortical damage.6
Although the exact pathophysiology of PSH has not been identified, most of the researchers believe that it is a result of disconnection between the cortical inhibitory centres and sympathetic control centre.6 A disruption of this pathway can result in disinhibited sympathetic firing which then causes autonomic storming; these episodes are often triggered by non-noxious stimuli such as turning or suctioning.5 6 In addition, the patient’s extensor posturing further supports the theory of disconnection between higher modulatory centres and the vestibular nuclei. Abnormal positioning is often considered to have a poor prognosis, with fewer patients surviving after decerebrate posturing compared with decorticate posturing.7
The exact aetiology of MBD remains unclear and therefore, there are no definitive guidelines for therapy. Treatment with thiamine and other B complex vitamins has proved beneficial in most cases.1 There has also been a favourable response in some patients treated with corticosteroids.4 In addition to giving our patient high-dose intravenous thiamine and folic acid, we also added oral vitamin C and E due to their known antioxidative and neuroprotective properties, respectively.8 While most patients with MBD responded to intravenous thiamine and folic acid within 3–5 days,1 9 our patient turned around almost immediately within 48 hours of treatment. Therefore, we believe the addition of vitamin C and E might have had provided a synergistic effect. This multivitamin treatment approach has also been reported in the literature, although very few cases.10 One limitation to our proposal is that we did not obtain baseline serum vitamin B and C (except for B12) levels before nor after treatment, although this would not have changed our management given the onset of his encephalopathy is rather acute.
The definitive diagnosis of MBD is based on neuroimaging, specifically brain MRI with evidence of pathological lesions in the corpus callosum. Callosal injuries appear hypointense on T1 and hyperintense on T2 imaging.4 The affected area will have oedema with or without demyelination, which appears as a high signal lesion on T2-weighted imaging (T2WI)/FLAIR and diffusion-weighted imaging.2 4 5 If the impairment becomes chronic, MRI will show atrophy and cystic transformation of the affected region.11 Lesions can also be found in other regions of the brain, such as the cerebral lobes, hemispheric white matter and basal ganglia.
This case is unique because there have been few reported cases of MBD treated with a combination of ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), in addition to the commonly used B complex vitamins. Patients who recover from MBD usually have residual symptoms, such as subsequent dementia.4 However, our patient had complete recovery to full function. This case highlights the importance of recognising other toxic insults, such as drug misuse, as a potential cause for MBD. Furthermore, it is important for physicians to recognise the characteristic neuroimaging findings of MBD and to subsequently treat any vitamin deficiency promptly to prevent coma or even death.
Learning points
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Marchiafava-Bignami disease is characterised by corpus callosum acute demyelination and necrosis and subsequent atrophy.
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MRI changes may involve structures other than the corpus callosum including brain, such as subcortical regions, cerebral lobes, hemispheric white matter and basal ganglia.
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Clinical features are variable depending on the extent of the injury and may include disturbance of consciousness, seizures and limb signs. More severe disease may progress to coma and death.
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There is no definitive guideline therapy for Marchiafava-Bignami disease, treatment remains supportive care with aggressive vitamin supplementation to prevent further deterioration.
Ethics statements
Patient consent for publication
Footnotes
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Contributors YZ and RM: Acquisition of data and drafting the manuscript. KC: Acquisition of imaging and annotation. LC: Drafting the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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