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A non-alcoholic patient with acute Marchiafava-Bignami disease associated with gynecologic malignancy: Paraneoplastic Marchiafava-Bignami disease?
Clinical Neurology and Neurosurgery 109 (2007) 505–508
Case report
A non-alcoholic patient with acute Marchiafava-Bignami disease associated with gynecologic malignancy: Paraneoplastic Marchiafava-Bignami disease? Yahya Celik a,∗ , Osman Temizoz b , Hakan Genchellac b , Bilge Cakir b , Talip Asil a b
a Trakya University School of Medicine, Department of Neurology, Edirne 22030, Turkey Trakya University School of Medicine, Department of Radiodiagnostic, Edirne 22030, Turkey
Received 11 April 2006; received in revised form 6 February 2007; accepted 15 February 2007
Abstract We report a 45-year-old, non-alcoholic woman with ovarian cancer who presented with acute impairment of consciousness. Cranial MRI revealed symmetrical and bilateral increased signal intensities of the corpus callosum and the dentate nucleus, without contrast enhancement. The findings are comparable with Marchiafava-Bignami disease (MBD), although pathological confirmation was not possible. Most of the reported cases of MBD are related to chronic ingestion of red wine and/or related with a nutritional cause. We suggest that this patient may suffer a MBD possible related to the ovarian cancer. © 2007 Elsevier B.V. All rights reserved. Keywords: Paraneoplastic syndrome; Marchiafava-Bignami disease; Ovarian cancer; Corpus callosum; Magnetic resonance imaging; White matter lesions; Cerebellar
1. Introduction Marchiafava-Bignami disease is a disease affecting mainly the corpus callosum. It was first described in wine-drinking Italian men with bad nutritional habits and characterized by different neurological symptoms. However, MBD has since been observed among persons of many nationalities, with consumption of different types of alcohol and non-alcoholics [1–4]. MBD involves generally genu and body of the corpus callosum, but can also be seen in the extra-callosal structures, such as cerebral cortex, anterior commissure, centrum semiovale, cingulate gyrus, and middle cerebellar peduncles [5,6]. MBD is mostly fatal and causes severe neurological deficits but cases with good outcome by vitamin replacement, cortisone, and symptomatic treatment have been reported [7–9]. The prognosis of MBD
∗ Corresponding author. Tel.: +90 284 2354145/90 533 3514023; fax: +392 902842357652. E-mail address: [email protected] (Y. Celik).
0303-8467/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2007.02.011
patients associated with extra-callosal involvement is much worse than those with only callosal involvement. MBD is clinically characterized by reduced consciousness, psychotic and affective symptoms, apathy, depression, epileptic seizure, hemiparesis, disconnection syndromes, and frequently coma and death. We present a case of non-alcoholic MBD with a history of cancer. To the best of our knowledge, we found in the literature no other case of MBD, not related to alcohol abuse and probably related to ovarian cancer. 2. Case report A 45-year-old, right-handed woman with stage IV inoperable ovarian cancer was consulted because of acute loss of consciousness at the Gynaecologic Department. Because the patient had inoperable ovarian cancer, she was treated symptomatically without surgery or chemotherapy. She had not been abusing alcohol. She was relatively asymptomatic and feeding oral until 2 days before. On neurological
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Y. Celik et al. / Clinical Neurology and Neurosurgery 109 (2007) 505–508
examination, she was drowsy and uncooperative. Spontaneous verbal production and repetition were absent but her other vital signs were stable. All of the extremities were extended with increased muscle tonus (hypertonia). The tendon reflexes were hyperactive. Plantar responses were extensor. The pupils were isocoric, and eye movements and light reflex appeared normal. Routine laboratory studies including serum electrolytes, glucose, plasma ammonia, lactate, pyruvate levels, liver–renal–thyroid function tests, artery blood gas analysis were unremarkable. Serum folic acid was low, serum B12 within the normal range. Serum CA 125 level was 131.5 U/mL (reference range, <36 U/mL). We could not measure paraneoplastic antibodies like anti-Hu, anti-Yo, and antiRi because these markers have not been evaluated in our laboratory. We could not send to a reference laboratory because of economical status of patient. The patient’s lupus anticoagulant was negative. Anticardiolipin antibody IgG (ELISA) and IgM were normal. Antinuclear antibody, rheumatoid factor, anti-dsDNA and cryoglobulin were negative. Serum C3 complement and C4 complement levels were normal. HBsAg, anti-HCV antibody and HCV-RNA (PCR) was negative. The EEG showed diffuse slowing (7–8 Hz). All the other laboratory studies, cerebral spinal fluid examination (There was no atypical cells and negative flow cytometry examination), ECG, and Chest X-ray yielded normal results. MR imaging demonstrated areas of high T2 signal intensity bilaterally in the corpus callosum and dentate nucleus showed increased signal intensity (Figs. 1–4). There was no contrast enhancement. Cerebral MR venography and angiography were normal. These neuro-radiological findings were compatible with Marchiafava-Bignami disease. Based on the diagnosis of MBD, intravenous fluid, vitamin B complex and methyl prednisolone 500 mg/day were administered. But her
Fig. 2. Axial T2 weighted cranial MRI revealed diffuse symmetric involvement of the corpus callosum and dentate nucleus.
Fig. 3. Axial T2 weighted cranial MRI revealed diffuse symmetric involvement of the dentate nucleus.
neurological status did not improve and she died due to acute respiratory failure 3 days after the coma presentation. An autopsy was refused by her family.
3. Discussion
Fig. 1. There was no contrast enhancement in the coronal T1 weighted cranial MRI.
MB disease or syndrome is a rare disorder characterized pathologically by an acute demyelination of the corpus callosum associated with poorly nourished chronic alcoholism but
Y. Celik et al. / Clinical Neurology and Neurosurgery 109 (2007) 505–508
Fig. 4. Coronal T2 weighted cranial MRI shows diffuse symmetric involvement of the corpus callosum.
is occasionally seen in nonalcoholic patients. Although the rate of alcoholism is 4–7%, total reported number of patients with MBD is between 250 and 300 in Europe [9]. While MBD has been found once in 10,000 brains associated with alcoholrelated diseases in Australia, its prevalence was reported as 0.21% in France [10]. MBD is reported more frequently after common usage of the neuro-radiological investigation. The corpus callosum can be involved in many acquired diseases and conditions. MRI is not only diagnostic for MBD but also helpful in differentiation of MBD from diseases, such as lymphoma, glioblastoma multiforme, diffuse axonal injury, multiple sclerosis, ischemic lesions, large periventricular spaces, acute disseminated encephalomyelitis, and hydrocephalus [11]. Paraneoplastic neurological syndromes associated with ovarian cancer are cerebellar degeneration, Lambert–Eaton myasthenic syndrome and dermatomyositis in literature [12–14]. MBD may present with impairment of consciousness, epileptic seizures, coma, fatal neurological findings, mental confusion, psychotic and emotional symptoms, depression, memory deficits, ataxia, mutism, alexia, agraphia, and aphasia. MBD is categorized into acute, subacute, and chronic forms as temporal classification by Brion in 1977 [15]. Heinrich et al. suggest the two clinicoradiologic subtypes of MBD. When there are early diffuse corpus callosum involvement and coma it is defined as type A. But type B is characterized by partially corpus callosal lesions and slightly impairment of consciousness. Type B has more favorable prognosis than type A. If there is extra-callosal involvement (cortical, cerebellar peduncule) in MBD the prognosis is worse [7].
507
Although MBD typically occurs in chronic alcoholics associated with nutritional disorders it is reported in four non-alcoholic patients [16–19]. It is thought that there might be different etiological factors besides alcoholism and nutritional deficiency. Acute onset coma in the malignancy may be associated with metabolic disorders (electrolyte imbalance, encephalopathy due to organ metastasis, such as liver, renal, lung, etc.), vascular (arterial or venous cerebral infarction, pulmonary emboli), cranial metastasis, encephalopathy due to chemotherapeutic agents, radiation necrosis, epileptic seizure. In the differential diagnosis cerebral metastasis excluded due to no contrast enhancement in the lesions and normal CSF finding [20]. Nevertheless, diagnosis of Marchiafava-Bignami disease, although it is probable, and not pathological proven related to the neoplastic pathology. There were no metabolic disorders, cerebral metastasis, cranial vascular disorders, usage of chemotherapy, and application of radiotherapy in to the patient. Interestingly, our patient did not drink alcohol product her life time. Diffuse callosal, extra-callosal involvement and serious impairment of consciousness were present in our patient and we defined as Type A according to the Heinrich classification. Although two MBD patients are reported alcoholism associated with malignity in the English literature, it was interesting that our patient has no history of alcohol usage and bad nutrition status. As a paraneoplastic syndrome, MBD must be taken in mind in the coma etiology of cancer patients. References [1] Celik Y. In: Preedy V, Watson R, editors. Marchiafava-Bignami disease in alcoholism. Elsevier Science & Technology Books; 2004. p. 713–8 [Chapter 55]. [2] Rickert CH, Karger B, Varchmin-Schultheiss K, Brinkmann B, Paulus W. Neglect-associated fatal Marchiafava-Bignami disease in a non-alcoholic woman. Int J Legal Med 2001;115(October (2)): 90–3. [3] Kosaka K, Aoki M, Kawasaki N, Adachi Y, Konuma I, Iizuka R. A non-alcoholic Japanese patient with Wernicke’s encephalopathy and Marchiafava-Bignami disease. Clin Neuropathol 1984;3(November–December (6)):231–6. [4] Leong AS. Marchiafava-Bignami disease in a non-alcoholic Indian male. Pathology 1979;11(April (2)):241–9. [5] Menegon P, Sibon I, Pachai C, Orgogozo JM, Dousset V. MarchiafavaBignami disease: diffusion-weighted MRI in corpus callosum and cortical lesions. Neurology 2005;65(August (3)):475–7. [6] Johkura K, Naito M, Naka T. Cortical involvement in MarchiafavaBignami disease. AJNR Am J Neuroradiol 2005;26(March (3)): 670–3. [7] Heinrich A, Runge U, Khaw AV. Clinicoradiologic subtypes of Marchiafava-Bignami disease. J Neurol 2004;251(September (9)):1050–9. [8] Helenius J, Tatlisumak T, Soinne L, Valanne L, Kaste M. MarchiafavaBignami disease: two cases with favourable outcome. Eur J Neurol 2001;8(May (3)):269–72. [9] Gerlach A, Oehm E, Wattchow J, Ziyeh S, Glocker FX, Els T. Use of high-dose cortisone in a patient with Marchiafava-Bignami disease. J Neurol 2003;250(June (6)):758–60.
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Y. Celik et al. / Clinical Neurology and Neurosurgery 109 (2007) 505–508
[10] Hauw JJ, De Baecque C, Hausser-Hauw C, Serdaru M. Chromatolysis in alcoholic encephalopathies. Pellagra-like changes in 22 cases. Brain 1988;111:843–57. [11] Uchino A, Takase Y, Nomiyama K, Egashira R, Kudo S. Acquired lesions of the corpus callosum: MR imaging. Eur Radiol 2006;16(April (4)):905–14. [12] Zivaljevic M, Popovic S, Vujkov T. Lambert–Eaton myasthenic syndrome – a rare manifestation of paraneoplastic syndrome in ovarian cancer – case report. Med Pregl 2005;58(September–October (9–10)):495–7. [13] Santillan A, Bristow RE. Paraneoplastic cerebellar degeneration in a woman with ovarian cancer. Nat Clin Pract Oncol 2006;3(February (2)):108–12 [quiz 1 p following 112]. [14] Ben-Zvi N, Shani A, Ben-Baruch G, Agmon-Levin N, Sthoeger Z, Huszar M, Ben-Arie A, Dgani R. Dermatomyositis following the diagnosis of ovarian cancer. Int J Gynecol Cancer 2005;15(November–December (6)):1124–6.
[15] Brion S. Marchiafava-Bignami disease. In: Vinken PJ, Bruyn GW, editors. Handbook of clinical neurology. North Holland: Amsterdam; 2006. p. 317–29. [16] Mas G, Gonzalez-Caballero G, Martinez-Ortiz MJ, Saez-Castan J. Marchiafava-Bignami disease in a non-alcoholic patient. Rev Neurol 2006;42(May (10)):637–8. [17] Rickert CH, Karger B, Varchmin-Schultheiss K, Brinkmann B, Paulus W. Neglect-associated fatal Marchiafava-Bignami disease in a nonalcoholic woman. Int J Legal Med 2001;115(October (2)):90–3. [18] Kosaka K, Aoki M, Kawasaki N, Adachi Y, Konuma I, Iizuka R. A non-alcoholic Japanese patient with Wernicke’s encephalopathy and Marchiafava-Bignami disease. Clin Neuropathol 1984;3(November–December (6)):231–6. [19] Leong AS. Marchiafava-Bignami disease in a non-alcoholic Indian male. Pathology 1979;11(April (2)):241–9. [20] Batchelor T. Neuro-oncology update: 2005. Curr Opin Neurol 2005;18(December (6)):631.
Case report
A non-alcoholic patient with acute Marchiafava-Bignami disease associated with gynecologic malignancy: Paraneoplastic Marchiafava-Bignami disease? Yahya Celik a,∗ , Osman Temizoz b , Hakan Genchellac b , Bilge Cakir b , Talip Asil a b
a Trakya University School of Medicine, Department of Neurology, Edirne 22030, Turkey Trakya University School of Medicine, Department of Radiodiagnostic, Edirne 22030, Turkey
Received 11 April 2006; received in revised form 6 February 2007; accepted 15 February 2007
Abstract We report a 45-year-old, non-alcoholic woman with ovarian cancer who presented with acute impairment of consciousness. Cranial MRI revealed symmetrical and bilateral increased signal intensities of the corpus callosum and the dentate nucleus, without contrast enhancement. The findings are comparable with Marchiafava-Bignami disease (MBD), although pathological confirmation was not possible. Most of the reported cases of MBD are related to chronic ingestion of red wine and/or related with a nutritional cause. We suggest that this patient may suffer a MBD possible related to the ovarian cancer. © 2007 Elsevier B.V. All rights reserved. Keywords: Paraneoplastic syndrome; Marchiafava-Bignami disease; Ovarian cancer; Corpus callosum; Magnetic resonance imaging; White matter lesions; Cerebellar
1. Introduction Marchiafava-Bignami disease is a disease affecting mainly the corpus callosum. It was first described in wine-drinking Italian men with bad nutritional habits and characterized by different neurological symptoms. However, MBD has since been observed among persons of many nationalities, with consumption of different types of alcohol and non-alcoholics [1–4]. MBD involves generally genu and body of the corpus callosum, but can also be seen in the extra-callosal structures, such as cerebral cortex, anterior commissure, centrum semiovale, cingulate gyrus, and middle cerebellar peduncles [5,6]. MBD is mostly fatal and causes severe neurological deficits but cases with good outcome by vitamin replacement, cortisone, and symptomatic treatment have been reported [7–9]. The prognosis of MBD
∗ Corresponding author. Tel.: +90 284 2354145/90 533 3514023; fax: +392 902842357652. E-mail address: [email protected] (Y. Celik).
0303-8467/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2007.02.011
patients associated with extra-callosal involvement is much worse than those with only callosal involvement. MBD is clinically characterized by reduced consciousness, psychotic and affective symptoms, apathy, depression, epileptic seizure, hemiparesis, disconnection syndromes, and frequently coma and death. We present a case of non-alcoholic MBD with a history of cancer. To the best of our knowledge, we found in the literature no other case of MBD, not related to alcohol abuse and probably related to ovarian cancer. 2. Case report A 45-year-old, right-handed woman with stage IV inoperable ovarian cancer was consulted because of acute loss of consciousness at the Gynaecologic Department. Because the patient had inoperable ovarian cancer, she was treated symptomatically without surgery or chemotherapy. She had not been abusing alcohol. She was relatively asymptomatic and feeding oral until 2 days before. On neurological
506
Y. Celik et al. / Clinical Neurology and Neurosurgery 109 (2007) 505–508
examination, she was drowsy and uncooperative. Spontaneous verbal production and repetition were absent but her other vital signs were stable. All of the extremities were extended with increased muscle tonus (hypertonia). The tendon reflexes were hyperactive. Plantar responses were extensor. The pupils were isocoric, and eye movements and light reflex appeared normal. Routine laboratory studies including serum electrolytes, glucose, plasma ammonia, lactate, pyruvate levels, liver–renal–thyroid function tests, artery blood gas analysis were unremarkable. Serum folic acid was low, serum B12 within the normal range. Serum CA 125 level was 131.5 U/mL (reference range, <36 U/mL). We could not measure paraneoplastic antibodies like anti-Hu, anti-Yo, and antiRi because these markers have not been evaluated in our laboratory. We could not send to a reference laboratory because of economical status of patient. The patient’s lupus anticoagulant was negative. Anticardiolipin antibody IgG (ELISA) and IgM were normal. Antinuclear antibody, rheumatoid factor, anti-dsDNA and cryoglobulin were negative. Serum C3 complement and C4 complement levels were normal. HBsAg, anti-HCV antibody and HCV-RNA (PCR) was negative. The EEG showed diffuse slowing (7–8 Hz). All the other laboratory studies, cerebral spinal fluid examination (There was no atypical cells and negative flow cytometry examination), ECG, and Chest X-ray yielded normal results. MR imaging demonstrated areas of high T2 signal intensity bilaterally in the corpus callosum and dentate nucleus showed increased signal intensity (Figs. 1–4). There was no contrast enhancement. Cerebral MR venography and angiography were normal. These neuro-radiological findings were compatible with Marchiafava-Bignami disease. Based on the diagnosis of MBD, intravenous fluid, vitamin B complex and methyl prednisolone 500 mg/day were administered. But her
Fig. 2. Axial T2 weighted cranial MRI revealed diffuse symmetric involvement of the corpus callosum and dentate nucleus.
Fig. 3. Axial T2 weighted cranial MRI revealed diffuse symmetric involvement of the dentate nucleus.
neurological status did not improve and she died due to acute respiratory failure 3 days after the coma presentation. An autopsy was refused by her family.
3. Discussion
Fig. 1. There was no contrast enhancement in the coronal T1 weighted cranial MRI.
MB disease or syndrome is a rare disorder characterized pathologically by an acute demyelination of the corpus callosum associated with poorly nourished chronic alcoholism but
Y. Celik et al. / Clinical Neurology and Neurosurgery 109 (2007) 505–508
Fig. 4. Coronal T2 weighted cranial MRI shows diffuse symmetric involvement of the corpus callosum.
is occasionally seen in nonalcoholic patients. Although the rate of alcoholism is 4–7%, total reported number of patients with MBD is between 250 and 300 in Europe [9]. While MBD has been found once in 10,000 brains associated with alcoholrelated diseases in Australia, its prevalence was reported as 0.21% in France [10]. MBD is reported more frequently after common usage of the neuro-radiological investigation. The corpus callosum can be involved in many acquired diseases and conditions. MRI is not only diagnostic for MBD but also helpful in differentiation of MBD from diseases, such as lymphoma, glioblastoma multiforme, diffuse axonal injury, multiple sclerosis, ischemic lesions, large periventricular spaces, acute disseminated encephalomyelitis, and hydrocephalus [11]. Paraneoplastic neurological syndromes associated with ovarian cancer are cerebellar degeneration, Lambert–Eaton myasthenic syndrome and dermatomyositis in literature [12–14]. MBD may present with impairment of consciousness, epileptic seizures, coma, fatal neurological findings, mental confusion, psychotic and emotional symptoms, depression, memory deficits, ataxia, mutism, alexia, agraphia, and aphasia. MBD is categorized into acute, subacute, and chronic forms as temporal classification by Brion in 1977 [15]. Heinrich et al. suggest the two clinicoradiologic subtypes of MBD. When there are early diffuse corpus callosum involvement and coma it is defined as type A. But type B is characterized by partially corpus callosal lesions and slightly impairment of consciousness. Type B has more favorable prognosis than type A. If there is extra-callosal involvement (cortical, cerebellar peduncule) in MBD the prognosis is worse [7].
507
Although MBD typically occurs in chronic alcoholics associated with nutritional disorders it is reported in four non-alcoholic patients [16–19]. It is thought that there might be different etiological factors besides alcoholism and nutritional deficiency. Acute onset coma in the malignancy may be associated with metabolic disorders (electrolyte imbalance, encephalopathy due to organ metastasis, such as liver, renal, lung, etc.), vascular (arterial or venous cerebral infarction, pulmonary emboli), cranial metastasis, encephalopathy due to chemotherapeutic agents, radiation necrosis, epileptic seizure. In the differential diagnosis cerebral metastasis excluded due to no contrast enhancement in the lesions and normal CSF finding [20]. Nevertheless, diagnosis of Marchiafava-Bignami disease, although it is probable, and not pathological proven related to the neoplastic pathology. There were no metabolic disorders, cerebral metastasis, cranial vascular disorders, usage of chemotherapy, and application of radiotherapy in to the patient. Interestingly, our patient did not drink alcohol product her life time. Diffuse callosal, extra-callosal involvement and serious impairment of consciousness were present in our patient and we defined as Type A according to the Heinrich classification. Although two MBD patients are reported alcoholism associated with malignity in the English literature, it was interesting that our patient has no history of alcohol usage and bad nutrition status. As a paraneoplastic syndrome, MBD must be taken in mind in the coma etiology of cancer patients. References [1] Celik Y. In: Preedy V, Watson R, editors. Marchiafava-Bignami disease in alcoholism. Elsevier Science & Technology Books; 2004. p. 713–8 [Chapter 55]. [2] Rickert CH, Karger B, Varchmin-Schultheiss K, Brinkmann B, Paulus W. Neglect-associated fatal Marchiafava-Bignami disease in a non-alcoholic woman. Int J Legal Med 2001;115(October (2)): 90–3. [3] Kosaka K, Aoki M, Kawasaki N, Adachi Y, Konuma I, Iizuka R. A non-alcoholic Japanese patient with Wernicke’s encephalopathy and Marchiafava-Bignami disease. Clin Neuropathol 1984;3(November–December (6)):231–6. [4] Leong AS. Marchiafava-Bignami disease in a non-alcoholic Indian male. Pathology 1979;11(April (2)):241–9. [5] Menegon P, Sibon I, Pachai C, Orgogozo JM, Dousset V. MarchiafavaBignami disease: diffusion-weighted MRI in corpus callosum and cortical lesions. Neurology 2005;65(August (3)):475–7. [6] Johkura K, Naito M, Naka T. Cortical involvement in MarchiafavaBignami disease. AJNR Am J Neuroradiol 2005;26(March (3)): 670–3. [7] Heinrich A, Runge U, Khaw AV. Clinicoradiologic subtypes of Marchiafava-Bignami disease. J Neurol 2004;251(September (9)):1050–9. [8] Helenius J, Tatlisumak T, Soinne L, Valanne L, Kaste M. MarchiafavaBignami disease: two cases with favourable outcome. Eur J Neurol 2001;8(May (3)):269–72. [9] Gerlach A, Oehm E, Wattchow J, Ziyeh S, Glocker FX, Els T. Use of high-dose cortisone in a patient with Marchiafava-Bignami disease. J Neurol 2003;250(June (6)):758–60.
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Y. Celik et al. / Clinical Neurology and Neurosurgery 109 (2007) 505–508
[10] Hauw JJ, De Baecque C, Hausser-Hauw C, Serdaru M. Chromatolysis in alcoholic encephalopathies. Pellagra-like changes in 22 cases. Brain 1988;111:843–57. [11] Uchino A, Takase Y, Nomiyama K, Egashira R, Kudo S. Acquired lesions of the corpus callosum: MR imaging. Eur Radiol 2006;16(April (4)):905–14. [12] Zivaljevic M, Popovic S, Vujkov T. Lambert–Eaton myasthenic syndrome – a rare manifestation of paraneoplastic syndrome in ovarian cancer – case report. Med Pregl 2005;58(September–October (9–10)):495–7. [13] Santillan A, Bristow RE. Paraneoplastic cerebellar degeneration in a woman with ovarian cancer. Nat Clin Pract Oncol 2006;3(February (2)):108–12 [quiz 1 p following 112]. [14] Ben-Zvi N, Shani A, Ben-Baruch G, Agmon-Levin N, Sthoeger Z, Huszar M, Ben-Arie A, Dgani R. Dermatomyositis following the diagnosis of ovarian cancer. Int J Gynecol Cancer 2005;15(November–December (6)):1124–6.
[15] Brion S. Marchiafava-Bignami disease. In: Vinken PJ, Bruyn GW, editors. Handbook of clinical neurology. North Holland: Amsterdam; 2006. p. 317–29. [16] Mas G, Gonzalez-Caballero G, Martinez-Ortiz MJ, Saez-Castan J. Marchiafava-Bignami disease in a non-alcoholic patient. Rev Neurol 2006;42(May (10)):637–8. [17] Rickert CH, Karger B, Varchmin-Schultheiss K, Brinkmann B, Paulus W. Neglect-associated fatal Marchiafava-Bignami disease in a nonalcoholic woman. Int J Legal Med 2001;115(October (2)):90–3. [18] Kosaka K, Aoki M, Kawasaki N, Adachi Y, Konuma I, Iizuka R. A non-alcoholic Japanese patient with Wernicke’s encephalopathy and Marchiafava-Bignami disease. Clin Neuropathol 1984;3(November–December (6)):231–6. [19] Leong AS. Marchiafava-Bignami disease in a non-alcoholic Indian male. Pathology 1979;11(April (2)):241–9. [20] Batchelor T. Neuro-oncology update: 2005. Curr Opin Neurol 2005;18(December (6)):631.