This study reviewed 153 cases of Marchiafava–Bignami disease (MBD) and 53 cases of conditions mimicking MBD that were diagnosed using MRI or CT. The key findings were:
1) MBD patients were older, more often male alcoholics with malnutrition, while mimics were younger with various causes like infections or epilepsy.
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3) Lesions in MBD often involved multiple areas of the corpus callosum and were associated with poorer outcomes, while mimics typically had solitary splenium lesions.
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Marchiafava–Bignami disease (MBD)
1. J Neurol Neurosurg Psychiatry
Diagnosis and management of Marchiafava–Bignami disease: a
review of CT/MRI confirmed cases
Matti Hillbom, Pertti Saloheimo, Shinsuke Fujioka,, Zbigniew K
Wszolek ,Seppo Juvela, Maurizio A Leone
J Neurol Neurosurg Psychiatry 2014;85:168-173
doi:10.1136/jnnp-2013-305979
2. BACKGROUND
• Marchiafava–Bignami disease (MBD) a rare, fatal disease
affecting wine drinkers.
• Characterised by demyelination and necrosis of the corpus
callosum,
• Either a toxic or nutritional etiology
• Non-fatal outcomes and other entities closely mimicking the
disease have also been described
• Some non-alcoholics also have phenotypic and radiological
findings that are typical of MBD
• The accuracy of the diagnosis and outcome influenced by
stage of disease
3. OBJECTIVES
• To define essential features for correct diagnosis
of MBD
• To identify features for differential diagnosis
from mimicking conditions of MBD
• To find efficient treatment
4. STUDY DESIGN
• The databases of PubMed, Biomedical Database (EMBASE),
Scopus and Lilacs Express
• From 1981 to January 2012 for papers containing the
keyword ‘Marchiafava–Bignami’ either the title or the
abstract.
• Total of 153 MBD
• 84 were from Europe(France: 41, Spain: 17, Germany: 8, Italy: 4, Turkey: 3,
Finland: 3, Switzerland: 2, Poland: 2, the Netherlands: 1, Belgium: 1, Austria: 1 and
Portugal: 1)
• 78 from outside Europe (Japan: 42, India: 11, USA: 8, Korea: 5, China: 4,
Thailand: 3, Mexico: 2, Uruguay: 2 and Brazil: 1)
• Cases that were reported in more than one paper were
considered only once
5. Patients and Methods
• A total of 153 MBD cases ,all of which had been diagnosed
using either head MRI or CT ante mortem.
• Associated with alcoholism, malnutrition or both.
• Alcoholics include subjects described either to be chronic
current alcoholics (n=82) or dependent on alcohol (n=6)
and others (n=54) who were reported to be chronic
excessive alcohol consumers with a long history of alcohol
abuse or heavy drinking habits
6. MBD mimicking lesion
MRI-verified, reversible, callosal lesions
which not associated with alcoholism or malnutrition
keywords: corpus callosum, reversible lesion
53 Total case
23 subjects with a cerebral infection, 14 with epilepsy, 5 with
hypoglycaemia and 11 with miscellaneous conditions
7. Data extraction
Signs and symptoms on admission and during the course of the disease
Time from symptom onset to the last clinical observation
Outcome attributable to MBD (Glasgow Outcome Scale (GOS))
Delay from the onset of symptoms to admission, acute (≤2 weeks) or
sub-acute (>2 weeks)
Location of the corpus callosum lesions that were observed at the first
and second examinations post admission and those observed during the
chronic phase (>3 months after admission)
8. OTHER INVESTIGATION:
MRI features; positron emission tomography (PET); single photon
emission CT (SPECT); MRI spectroscopy
Laboratory tests, including blood thiamine and cerebrospinal
fluid, drug treatment (thiamine, other vitamins and steroids); drug
doses, timing and mode of drug administration (parenteral or oral)
Wernicke's disease (diagnosed either clinically, by radiology or at
autopsy); and diabetes.
If data on given signs, symptoms or other items of information were
missing from the report, then the feature concerned was considered
absent.
9. Statistical analysis
Categorical variables were compared using Fisher’s exact two-tailed
test and the Pearson χ2test, while the continuous variables were
compared between groups by means of the Mann–Whitney U-test or
Student's t test.
Unconditional logistic regression was used to search for factors that
were associated with a poor outcome (severe disability or worse
outcome according to GOS) in subjects with MBD.
10. RESULT
Demographic and clinical characteristics of subjects with Marchiafava–Bignami disease
(MBD) or a condition mimicking it
MBD cases
153
MBD mimics
53*
Mean age at onset, years
(95% CI)
Men, n (%)
Alcoholism (%)
Malnutrition‡ (%)
48.4 (46.6 to 50.3)†
25.3 (20.4 to 30.3)
123 (80.4)†
142 (92.8)†
64 (39.8)†
28 (52.8)
0
0
Wernicke's disease (%)
19 (12.4)†
0
Thiamine treatment (%)
103 (67.3)†
3 (5.7)
Steroid treatment (%)
19 (12.4)
10 (18.9)
Diabetes (%)
10 (6.5)
6 (11.3)
Characteristic
*Includes 23 subjects with a cerebral infection, 14 with epilepsy, 5 with hypoglycaemia
and 11 with miscellaneous conditions
†p<0.01.
‡Malnutrition or prolonged vomiting without alcohol consumption in 11 cases
11. The MBD subjects were significantly older (p<0.001) than MBDmimics.
Both groups showed a wide age range (1–78 years for mimics vs
14–79 years for MBD).
The groups also differed significantly for other variables except
for presence of diabetes and treatment with steroids
12. Clinical symptoms and signs in MRI of subjects with Marchiafava–Bignami disease
(MBD) or a condition mimicking it
MBD cases n=153
MBD mimics n=53
Symptom/sign
n (%)
n (%)
Altered mental state
Impaired walking
Loss of consciousness
Dysarthria
Impaired memory
Signs of disconnection
Pyramidal sign
Seizures
Primitive reflexes
Mutism
Rigidity
Hemiparesis or tetraparesis
123 (80.4)***
104 (68.0)***
80 (52.3)***
62 (40.5)***
59 (38.6)***
55 (35.9)***
37 (24.2)***
32 (20.9)
30 (19.6)**
28 (18.3)*
25 (16.3)**
22 (14.4)
13 (24.5)
5 (9.4)
9 (17.0)
5 (9.4)
2 (3.8)
1 (1.9)
1 (1.9)
17 (32.1)
1 (1.9)
2 (3.8)
0
7 (13.2)
Sensory symptoms
Incontinence
Nystagmus
Ophthalmoplegia or gaze
palsy
Facial palsy
21 (13.7)*
17 (11.1)**
15 (9.8)
1 (1.9)
0
4 (7.5)
15 (9.8)*
0
8 (5.2)
1 (1.9)
***p<0.001, **p<0.01, *p<0.05 for difference between cases and mimics.
13. Signs and symptoms
The MBD patients frequently showed an altered mental state, which included
confusion, delirium, unconsciousness, impaired memory and/or disorientation
on admission.
Impaired walking, dysarthria, mutism, signs of disconnection or split brain
syndrome, pyramidal signs, primitive reflexes, rigidity, incontinence, sensory
symptoms and gaze palsy or diplopia were also more frequently found in the
MBD cases than in the MBD mimics.
Hemiparesis or tetraparesis and nystagmus were almost as frequent, and
seizures were more frequent among the mimics.
CSF data were available for 62 MBD subjects and 25 mimics which showed
CSF proteins 5/62 (8.1%) and cells in and 0/62 of the MBD Subjects
CSF proteins in 2/25 (8.0%) and cells in 9/25 (36.0%) of the mimics.
Elevated CSF cell content was always due to central nervous system infection.
15. Lesions
Only 17/61 (27.9%) of those visible in the acute phase disappeared completely
23/61 (37.7%) disappeared partially in the follow-up MRIs in MBD.
Lesions outside the splenium very rare in the mimicking cases (2/53,3.8%)
The MBD mimic lesions usually disappeared within a week; residual MRI lesions
were seen in only 2/47 (4.3%)
Callosal atrophy (n=36) or necrosis (n=45) was frequently reported among the
subjects with MBD, whereas no such findings among mimics
Deep white matter lesions (60/121, 49.6% (p=0.007) and cortical lesions 32/104,
30.8%) (p=0.003) were significantly more frequent in the subjects MBD compared
with the mimics (6/28, 21.4% and 1/27, 3.7%)
Lesions that were enhanced by gadolinium were frequently reported in the
subjects with MBD (16/90, 17.8%), but this was not found in the mimics.
16. Demographic features of alcoholic versus non-alcoholic
MBD subjects
11 subjects in this series (7.2%) non alcoholics and have MBD
The non-alcoholic subjects with MBD were younger and were
more frequently women
The non-alcoholics always suffering from malnutrition or
prolonged vomiting.
Nutritional state was reported for only 66/142 alcoholics; 53
(80.3%) of whom were said to be suffering from malnutrition.
The nutritional state of the alcoholics with MBD did not differ
significantly from the non-alcoholics.
17. Outcome for 144 patients with Marchiafava–Bignami disease (MBD), by mode of
treatment
Treated with
Not treated with Treated with
thiamine n=103 thiamine n=41* steroids n=19
Not treated with
steroids n=125*
n (%)
17 (16.5)
n (%)
4 (8.0)
n (%)
4 (21.1)
n (%)
17 (13.6)
24 (23.3)
6 (12.0)
1 (5.3)
29 (23.2)
29 (28.2)
12 (24.0)
5 (26.3)
36 (28.8)
Severe disability 18 (17.5)
7 (14.0)
5 (26.3)
20 (16.0)
Vegetative state
3 (2.9)
2 (4.0)
1 (5.3)
4 (3.2)
Dead
12 (11.7)
10 (20.0)
3 (15.8)
19 (15.2)
Outcome
Normal
Minimal
disability
Moderate
disability
p=0.027 for the difference in linear trend between the thiamine and outcome groups.
*Not treated or information on treatment not available.
18. Effect of treatment on the outcome for MBD subjects
Data available for 144/153 MBD subjects
Better outcomes among those who were treated with thiamine (p=0.027)
Treatment with steroids not show any significant trend.
The outcome of the subjects who receive thiamine in the acute phase of
the disease have significantly better (p=0.026) than those treated in the
chronic phase.
Blood thiamine levels on admission reported 20/153 (13.1%) subjects
with MBD and for 5/53 (9.4%) of those with a condition mimicking
MBD.
Below normal were observed in 16/20 (80.0%) MBD cases and 1/5
(20.0%) MBD mimic cases, respectively (p=0.023).
Thiamine given by infusion in 60/103 MBD subjects and orally to 3
MBD
Data not available for 40 MBD patients.
Duration of thiamine treatment ranged from 1 to 105 days.
19. Outcome
The outcome not reported in 15 MBD patients.
More than half of the non-alcoholics (7/11, 63.6%) recovered completely
Only one alcoholic in every 10 (14/142, 9.9%) showed a good outcome.
Death equal in both groups.
The outcome of MBD mimics good, most (45, 84.9%) normal or having
minimal disability after recovering from the acute phase of disease.
25 MBD subjects with a solitary lesion in the splenium, 3 (12%) had poor
outcome (severe disability), while of 105 subjects with other lesions, 39
(37.1%) had poor outcome (19 with severe disability, five with vegetative state
and 15 died) (p=0.016).
20. Discussion
MBD and MBD mimics had different clinical features and radiological findings.
Outcome in MBD extremely variable and influenced by lesion location and by the
timing of thiamine treatment.
MBD observed with alcoholism, malnutrition or Wernicke's disease
MBD mimics are usually not associated with these factors, but rather with
cerebral infection, epilepsy, antiepileptic drug withdrawal, hypoglycaemia,high altitude
sickness and systemic lupus erythematosus
Subjects with MBD often show severe signs and symptoms, including an altered
mental state, impaired walking, deficient memory, dysarthria, pyramidal signs and
disconnection lasting for several weeks.
MBD also show slow recovery, whereas the signs and symptoms of mimicking
conditions are usually mild and disappear within a week.
Delirious behaviour, disturbed consciousness and seizures are common features of
both MBD and the MBD mimics; however, seizures seem to occur even more
frequently in the MBD mimics.
21. The lesions in the MBD mimics are usually located in the splenium, whereas single
splenial lesions are seen only in one third of the MBD subjects.
MBD lesions enhanced by gadolinium, but no lesion enhancement in the MBD
mimics.
Solitary splenial lesions were associated with better outcome than lesions located in
other parts or across the entire corpus callosum.
MR spectroscopy has revealed an increase in choline/creatine, indicating
demyelination during the early phase of the disease followed by a decrease in Nacetylaspartate/creatine, indicating axonal damage.
Diffusion tensor imaging (DTI) employed for clinical course of MBD and the
recovery process
Thiamine therapy justified and recommendable as a first line of treatment for cases of
MBD associated with alcoholism, malnutrition or prolonged vomiting and even for
MBD mimics in case their thiamine levels are below normal.
22. LACUNAE
• The major limitation of this study lack of complete data.
• Many of the case reports included incomplete data on the
clinical status, the treatment and the outcome of cases.
• Case reports on MBD mimics not in a systematic manner, the
results no more than suggestive.
• There are a growing number of diseases and conditions that
have transient lesions in the splenium of the corpus callosum
associated with them, but the pathophysiology of these lesions
unclear.
• Difficult to prove the efficacy of therapy, whether combined
with steroids or not in a placebo-controlled randomised trial,
because the condition is very rare
23. TAKE HOME MESSAGE
• First: Choice of imaging in MBD is DWI, and recovery monitored
DTI and fibre tracking.
• Second:high frequency of thiamine deficiency among alcoholics
(even not suffering caloric malnutrition) and malnourished people
(who have prolonged vomiting),therapy with parenteral thiamine
indicated.
• The dose of thiamine should be the same as recommended for
Wernicke's disease and the therapy should continue for as long as
recovery is going on.
24. Applicability and application
• Is the study population relevant to my practice
and patients?
Yes
• Are the patients in my practice similar to those
in the study?
Yes
25. Relevance
• Is this problem common in my practice?
Yes/No
• Will this information require to change my
current practice?
• Yes/No
26. CRITICAL APPRAISAL
• Did study address the focused question ?
yes
• Was there a comparision group?
yes
• Were the groups comparable at baseline ?
No
• Was outcome measured by blind assessors ?
no
27. CRITICAL APPRAISAL
• How precise were the results ?
Precise enough.
• Are all clinically relevant outcome considered?
yes
• Can results be applied on our population ?
yes
Editor's Notes
The MBD subjects were significantly older (p<0.001) than MBD-mimics. Both groups showed a wide age range (1–78 years for mimics vs 14–79 years for MBD). The groups also differed significantly for other variables except for presence of diabetes and treatment with steroids