- Email: [email protected]
Central pontine myelinolysis in a patient with bulimia: Case report and literature review
Clinical Neurology and Neurosurgery 192 (2020) 105722
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Central pontine myelinolysis in a patient with bulimia: Case report and literature review
T
Tim Vladimirova,*, Mirjam Dreikorna, Karin Stahla, Andreas Müllerb, Jürgen Hupea, Peter Krafta,c,* a
Department of Neurology, Hospital Main-Spessart, Grafen-von-Rieneck-Str. 5, 97816, Lohr, Germany Practice for Radiology and Neuroradiology, Grafen-von-Rieneck-Str. 5, 97816, Lohr, Germany c University Clinic Würzburg, Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany b
1. Introduction From a pathophysiological perspective, CPM is characterized by symmetric demyelination of axons in the central part of the pons. The clinical course may vary from asymptomatic cases to severe tetraparesis, pseudobulbar palsy, coma and ultimately death. Initially, symptoms can be unspecific and might be misinterpreted as functional impairment [1,2], especially in patients with eating and other psychiatric disorders, making a correct and rapid diagnosis sometimes challenging. 2. Case report We describe a case of a 24-year-old woman with recurrent hyponatremia and hypokalemia in the context of bulimia nervosa beginning at the age of 19. The medical history is also positive for suicide attempts, depressive episodes, alcoholism and drug abuse. During the last episode of hyponatremia and hypokalemia that occurred after provoked vomiting, she collapsed and was transferred to an internal medicine ward where decreased sodium (113 mmol/l) and potassium levels (1.9 mmol/l) were measured. Therefore, cautious substitution of electrolytes with NaCl began. In addition, vitamin B1 and B6 were substituted due to low levels. The patient was treated and monitored on an Intensive Care Unit. Electrolytes slowly increased (day 4: sodium 135 mmol/l, potassium 4.0 mmol/l). Following an episode of reduced alertness, 2 days after admission a cranial MRI has been performed that displayed no clear signal alterations typical for pontine or extrapontine myelinolysis. The clinical status of the patient improved, but due to suicidal tendencies she was transferred to a Psychiatric Clinic where an initial normal neurological examination has been documented. Beginning from the 4th day in the Psychiatry on, the patient developed slowly progressive stand, gait and limb ataxia.
⁎
Three days later, she was transferred to our Department of Neurology where saccadic eye movements, ataxia, dysarthrophonia and dysphagia were observed on the day of admission. Blood tests showed increased lipase, with no other evidence of pancreatitis. Sodium was normal (141 mmol/l) and potassium was slightly decreased (3.14 mmol/l). Cerebrospinal fluid (CSF) analysis did not show any pathological findings. On day 6 of the hospitalization in our department, we performed a cranial MRI, which showed a signal alteration in the brain stem indicative for central pontine myelinolysis (Fig. 1A–D). A probatory anti-inflammatory treatment with methylprednisolone for 3 days had no effect. A subsequent control CSF analysis again did not show any pathological abnormalities. Symptoms continued to worsen, reaching severe tetraparesis. Deterioration of dysphagia required the placement of a nasogastric tube, and communication with the patient was only possible through "Yes/No-code" by movements of her head. An aspiration pneumonia developed and had to be treated with antibiotics. After 10 days of treatment in our Neurology department, the patient was transferred to a rehabilitation clinic. According to the information from there, a slight improvement of motor functions and dysarthria has been observed over several weeks. Nasogastric nutrition has been replaced by thickened oral food and fluids. Stabilization also of her emotional state has been reported. 3. Discussion CPM was first described 1959 as a disease that occurs in alcoholismassociated malnutrition [3]. Nevertheless, the rarity of CPM associated with eating disorders impedes controlled studies. Our goal was to collect and analyze available data from case reports. Our review was conducted in the Pubmed database on December 15th 2018 with the search words: ((central pontine myelinolysis) OR
Corresponding authors at: Department of Neurology, Hospital Main-Spessart, Grafen-von-Rieneck-Str. 5, 97816, Lohr, Germany. E-mail addresses: [email protected] (T. Vladimirov), [email protected] (P. Kraft).
https://doi.org/10.1016/j.clineuro.2020.105722 Received 3 May 2019; Received in revised form 13 January 2020; Accepted 4 February 2020 Available online 05 February 2020 0303-8467/ © 2020 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 192 (2020) 105722
T. Vladimirov, et al.
Fig. 1. A: Axial FLAIR-imaging shows slightly hyperintense signal in the central pons (arrow), representing pontine edema. B: Axial Diffusion-weighted-imaging (DWI) shows acute hyperintensity and diffusion restriction, with a pattern that precisely matches the hyperintensity on FLAIR imaging (arrow). C, D: Axial T1 imaging after i.v. gad infusion (C) demonstrates faint enhancement of the demyelinating area, best seen in the substraction images (arrow) (D).
(osmotic demyelinating syndrome)) and (((eating disorder) OR bulimia) OR anorexia). The initial result included 18 articles. Additional inclusion criteria were English language of the article and individuals over 18 years of age. After exclusion of articles that did not meet these criteria, 8 articles remained [1,2,4–9]. CPM is observed mostly in alcoholics and patients with history of liver transplant, malnutrition, polydipsia and/or diuretic abuse. The presence of unexpected neuropsychiatric symptoms in these disease conditions are red flags for CPM. However, in patients with eating disorders, in some cases the occurrence of neuropsychiatric symptoms might be underestimated due to assumption of a functional origin of clinical signs [1,2]. Our review shows that the main causes of hospitalization of patients with eating disorders that consequently develop CPM are hyponatremia, hypokalemia and metabolic alkalosis, although there is one case
described with development of CPM due to hypoglycemic coma in a patient with anorexia nervosa [4]. CPM related lesions are best visualized by MRI scan. However, clinical symptoms may precede MRI changes [1,5]. All conducted CT scans from case reports in our review were without pathological abnormalities [1,2,4,6]. We present a summary of case reports of this review in Table 1. 4. Conclusion Patients with preexisting eating disorders likely have an increased risk to develop CPM. Therefore, in case of electrolyte imbalance correction must be carried out with utmost importance and laboratory as well as clinical monitoring.
2
Age/sex
23/F
28/F
44/F
24/F
31/M
24/F
32/F
35/F
Author
Patel et al. [1]
Bando et al. [4]
Singer et al. [7]
Steckler et al. [6]
Sugimoto et al. [8]
3
Amann et al. [5]
Greenberg et al. [9]
Copeland et al. [2]
19-year history of eating disorder (anorexia nervosa with episodes of bulimia) Laxative abuse, anorexia nervosa, bulimia, alcohol abuse
8-year history of anorexia nervosa and polydipsia
Anorexia, binge eating, and selfinduced vomiting
10-year history of bulimia
7-year history of anorexia and bulimia nervosa Long history of selfinduced vomiting, use of laxatives and diuretics
7-year history of anorexia nervosa
Eating disorder
91 mmol/L
K 1.6 mmol/L, Cl 46 mmol/L, HCO3 33
K 1.5 mmol/L, Cl 60 mmol/L, HCO3 41 mmol/L
101 mmol/L
90 mmol/L
K 2.8 mmol/L, increased serum renin and aldosterone and hypokalemic alkalosis K 1.6 mmol/L
K 1.8 mmol/L, Chloride 52 mmol/L
n.a.
K 3.3 mmol/L, hypoglycemia (16 mg/dl)
K 1.6 mmol/L
Initial levels of other parameters
140 mmol/L
112 mmol/L
115 mmol/L
140 mmol/L
108 mmol/L
Initial sodium levels
Up to 103 mmol/L within 6.5 hours
Up to 114 mmol/L within 9 hours and 126 mmol/L within 34 hours
Up to 118 mmol/L within 24 hours and and 128 mmol/L within 4 days
n.a.
Up to 136 mmol/L within 28 hours
Up to 145 mmol/L within 3 days
n.a.
Up to 130 mmol/L within 12h
Sodium correction
After 6 days: persistent confusion, dysarthria, ataxia, saccadic eye movements, increased symmetric muscle reflexes, Babinski’s sign negative 10 days after admission: dizziness, weakness, shortness of breath. Over the next several days: tetraparesis, inability to cough or articulate, dysphagia After 5 days: personality changes. After 10 days: dysphagia, spasticity and flexion contractures of the ankles
6 days after electrolytes correction: confused, worsening mobility, “childlike behavior“, dysphagia, dysarthria, mutism, GCS 10 Dysarthria, dysgraphia and gait disturbance, ataxia, positive Babinski’s sign 16 days after initial presentation: tetraparesis with rigidity in all four extremities, facial diplegia, anarthria, dysphagia, and bilateral positive Babinski’s sign 20 days after discharge: ataxia, dysphagia, motor strength 4/5 in the upper extremities, emotional lability Asymptomatic
Clinical symptoms
Normal CT scan 5 days after admission, but MRI 20 days after admission showed CPM
MRI scan with gadolinium enhancement 8 days after admission revealed a low density, nonenhancing pontine lesion
T2 hyperintensity in central pons
Symmetric T2 hyperintensity in the mid and upper pons and the lower mesencephalon without mass effect T2 hyperintensity in central pons 2 months after admission
T2 hyperintensity in the central pons and diffusely throughout the white matter of both hemispheres. The putamen, caudate nuclei, and thalami also involved.
T1-hypointense and T2-hyperintens central pons lesion without mass effect
T2-hyperintense lesions in the central pons
MRI findings
Table 1 Overview of the available case reports of CPM in context with eating disorders. ADL, activities of daily living; MRI, magnetic resonance imaging; n.a., not applicable.
Able to walk after 2 months, speech restored months later
Good motor recovery within 2 months
3 months later: slight dysarthria, mild cognitive dysfunction
MRI normalization 6 months after admission
n.a.
Slowly improving, still requiring assistance for all ADL after 6 weeks, independent for ADL after 7 months
Gradual clinical improvement
n.a.
Follow-up
T. Vladimirov, et al.
Clinical Neurology and Neurosurgery 192 (2020) 105722
Clinical Neurology and Neurosurgery 192 (2020) 105722
T. Vladimirov, et al.
Funding
[3] R.D. Adams, M. Victor, E.L. Mancall, Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients, AMA Arch. Neurol. Psychiatry 81 (1959) 154–172. [4] N. Bando, K. Watanabe, M. Tomotake, T. Taniguchi, T. Ohmori, Central pontine myelinolysis associated with a hypoglycemic coma in anorexia nervosa, Gen. Hosp. Psychiatry 27 (2005) 372–374. [5] B. Amann, M. Schäfer, A. Sterr, S. Arnold, H. Grunze, Central pontine myelinolysis in a patient with anorexia nervosa, Int. J. Eat. Disord. 30 (2001) 462–466. [6] T.L. Steckler, Central pontine myelinolysis in a patient with bulimia, South. Med. J. 88 (1995) 858–859. [7] C. Singer, D. Lorenzo, S. Papapetropoulos, A. Mesa, B. Bowen, Pontine/extrapontine myelinolysis occurring in the setting of an eating disorder, Neurology 64 (2005) 2156–2157. [8] T. Sugimoto, T. Murata, M. Omori, Y. Wada, Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa, J. Neurol. Neurosurg. Psychiatry 74 (2003) 353–355. [9] W.M. Greenberg, P.J. Shab, M. Vakharia, Anorexia nervosa/bulimia and central pontine myelinolysis, Gen. Hosp. Psychiatry 14 (1992) 357–358.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Competing Interest None. References [1] A.S. Patel, L. Matthews, W. Bruce-Jones, Central pontine myelinolysis as a complication of refeeding syndrome in a patient with anorexia nervosa, J. Neuropsychiatry Clin. Neurosci. 20 (2008) 371–373. [2] P.M. Copeland, Diuretic abuse and central pontine myelinolysis, J. Psychother. Psychosomatics 52 (1989) 101–105.
4
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Central pontine myelinolysis in a patient with bulimia: Case report and literature review
T
Tim Vladimirova,*, Mirjam Dreikorna, Karin Stahla, Andreas Müllerb, Jürgen Hupea, Peter Krafta,c,* a
Department of Neurology, Hospital Main-Spessart, Grafen-von-Rieneck-Str. 5, 97816, Lohr, Germany Practice for Radiology and Neuroradiology, Grafen-von-Rieneck-Str. 5, 97816, Lohr, Germany c University Clinic Würzburg, Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany b
1. Introduction From a pathophysiological perspective, CPM is characterized by symmetric demyelination of axons in the central part of the pons. The clinical course may vary from asymptomatic cases to severe tetraparesis, pseudobulbar palsy, coma and ultimately death. Initially, symptoms can be unspecific and might be misinterpreted as functional impairment [1,2], especially in patients with eating and other psychiatric disorders, making a correct and rapid diagnosis sometimes challenging. 2. Case report We describe a case of a 24-year-old woman with recurrent hyponatremia and hypokalemia in the context of bulimia nervosa beginning at the age of 19. The medical history is also positive for suicide attempts, depressive episodes, alcoholism and drug abuse. During the last episode of hyponatremia and hypokalemia that occurred after provoked vomiting, she collapsed and was transferred to an internal medicine ward where decreased sodium (113 mmol/l) and potassium levels (1.9 mmol/l) were measured. Therefore, cautious substitution of electrolytes with NaCl began. In addition, vitamin B1 and B6 were substituted due to low levels. The patient was treated and monitored on an Intensive Care Unit. Electrolytes slowly increased (day 4: sodium 135 mmol/l, potassium 4.0 mmol/l). Following an episode of reduced alertness, 2 days after admission a cranial MRI has been performed that displayed no clear signal alterations typical for pontine or extrapontine myelinolysis. The clinical status of the patient improved, but due to suicidal tendencies she was transferred to a Psychiatric Clinic where an initial normal neurological examination has been documented. Beginning from the 4th day in the Psychiatry on, the patient developed slowly progressive stand, gait and limb ataxia.
⁎
Three days later, she was transferred to our Department of Neurology where saccadic eye movements, ataxia, dysarthrophonia and dysphagia were observed on the day of admission. Blood tests showed increased lipase, with no other evidence of pancreatitis. Sodium was normal (141 mmol/l) and potassium was slightly decreased (3.14 mmol/l). Cerebrospinal fluid (CSF) analysis did not show any pathological findings. On day 6 of the hospitalization in our department, we performed a cranial MRI, which showed a signal alteration in the brain stem indicative for central pontine myelinolysis (Fig. 1A–D). A probatory anti-inflammatory treatment with methylprednisolone for 3 days had no effect. A subsequent control CSF analysis again did not show any pathological abnormalities. Symptoms continued to worsen, reaching severe tetraparesis. Deterioration of dysphagia required the placement of a nasogastric tube, and communication with the patient was only possible through "Yes/No-code" by movements of her head. An aspiration pneumonia developed and had to be treated with antibiotics. After 10 days of treatment in our Neurology department, the patient was transferred to a rehabilitation clinic. According to the information from there, a slight improvement of motor functions and dysarthria has been observed over several weeks. Nasogastric nutrition has been replaced by thickened oral food and fluids. Stabilization also of her emotional state has been reported. 3. Discussion CPM was first described 1959 as a disease that occurs in alcoholismassociated malnutrition [3]. Nevertheless, the rarity of CPM associated with eating disorders impedes controlled studies. Our goal was to collect and analyze available data from case reports. Our review was conducted in the Pubmed database on December 15th 2018 with the search words: ((central pontine myelinolysis) OR
Corresponding authors at: Department of Neurology, Hospital Main-Spessart, Grafen-von-Rieneck-Str. 5, 97816, Lohr, Germany. E-mail addresses: [email protected] (T. Vladimirov), [email protected] (P. Kraft).
https://doi.org/10.1016/j.clineuro.2020.105722 Received 3 May 2019; Received in revised form 13 January 2020; Accepted 4 February 2020 Available online 05 February 2020 0303-8467/ © 2020 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 192 (2020) 105722
T. Vladimirov, et al.
Fig. 1. A: Axial FLAIR-imaging shows slightly hyperintense signal in the central pons (arrow), representing pontine edema. B: Axial Diffusion-weighted-imaging (DWI) shows acute hyperintensity and diffusion restriction, with a pattern that precisely matches the hyperintensity on FLAIR imaging (arrow). C, D: Axial T1 imaging after i.v. gad infusion (C) demonstrates faint enhancement of the demyelinating area, best seen in the substraction images (arrow) (D).
(osmotic demyelinating syndrome)) and (((eating disorder) OR bulimia) OR anorexia). The initial result included 18 articles. Additional inclusion criteria were English language of the article and individuals over 18 years of age. After exclusion of articles that did not meet these criteria, 8 articles remained [1,2,4–9]. CPM is observed mostly in alcoholics and patients with history of liver transplant, malnutrition, polydipsia and/or diuretic abuse. The presence of unexpected neuropsychiatric symptoms in these disease conditions are red flags for CPM. However, in patients with eating disorders, in some cases the occurrence of neuropsychiatric symptoms might be underestimated due to assumption of a functional origin of clinical signs [1,2]. Our review shows that the main causes of hospitalization of patients with eating disorders that consequently develop CPM are hyponatremia, hypokalemia and metabolic alkalosis, although there is one case
described with development of CPM due to hypoglycemic coma in a patient with anorexia nervosa [4]. CPM related lesions are best visualized by MRI scan. However, clinical symptoms may precede MRI changes [1,5]. All conducted CT scans from case reports in our review were without pathological abnormalities [1,2,4,6]. We present a summary of case reports of this review in Table 1. 4. Conclusion Patients with preexisting eating disorders likely have an increased risk to develop CPM. Therefore, in case of electrolyte imbalance correction must be carried out with utmost importance and laboratory as well as clinical monitoring.
2
Age/sex
23/F
28/F
44/F
24/F
31/M
24/F
32/F
35/F
Author
Patel et al. [1]
Bando et al. [4]
Singer et al. [7]
Steckler et al. [6]
Sugimoto et al. [8]
3
Amann et al. [5]
Greenberg et al. [9]
Copeland et al. [2]
19-year history of eating disorder (anorexia nervosa with episodes of bulimia) Laxative abuse, anorexia nervosa, bulimia, alcohol abuse
8-year history of anorexia nervosa and polydipsia
Anorexia, binge eating, and selfinduced vomiting
10-year history of bulimia
7-year history of anorexia and bulimia nervosa Long history of selfinduced vomiting, use of laxatives and diuretics
7-year history of anorexia nervosa
Eating disorder
91 mmol/L
K 1.6 mmol/L, Cl 46 mmol/L, HCO3 33
K 1.5 mmol/L, Cl 60 mmol/L, HCO3 41 mmol/L
101 mmol/L
90 mmol/L
K 2.8 mmol/L, increased serum renin and aldosterone and hypokalemic alkalosis K 1.6 mmol/L
K 1.8 mmol/L, Chloride 52 mmol/L
n.a.
K 3.3 mmol/L, hypoglycemia (16 mg/dl)
K 1.6 mmol/L
Initial levels of other parameters
140 mmol/L
112 mmol/L
115 mmol/L
140 mmol/L
108 mmol/L
Initial sodium levels
Up to 103 mmol/L within 6.5 hours
Up to 114 mmol/L within 9 hours and 126 mmol/L within 34 hours
Up to 118 mmol/L within 24 hours and and 128 mmol/L within 4 days
n.a.
Up to 136 mmol/L within 28 hours
Up to 145 mmol/L within 3 days
n.a.
Up to 130 mmol/L within 12h
Sodium correction
After 6 days: persistent confusion, dysarthria, ataxia, saccadic eye movements, increased symmetric muscle reflexes, Babinski’s sign negative 10 days after admission: dizziness, weakness, shortness of breath. Over the next several days: tetraparesis, inability to cough or articulate, dysphagia After 5 days: personality changes. After 10 days: dysphagia, spasticity and flexion contractures of the ankles
6 days after electrolytes correction: confused, worsening mobility, “childlike behavior“, dysphagia, dysarthria, mutism, GCS 10 Dysarthria, dysgraphia and gait disturbance, ataxia, positive Babinski’s sign 16 days after initial presentation: tetraparesis with rigidity in all four extremities, facial diplegia, anarthria, dysphagia, and bilateral positive Babinski’s sign 20 days after discharge: ataxia, dysphagia, motor strength 4/5 in the upper extremities, emotional lability Asymptomatic
Clinical symptoms
Normal CT scan 5 days after admission, but MRI 20 days after admission showed CPM
MRI scan with gadolinium enhancement 8 days after admission revealed a low density, nonenhancing pontine lesion
T2 hyperintensity in central pons
Symmetric T2 hyperintensity in the mid and upper pons and the lower mesencephalon without mass effect T2 hyperintensity in central pons 2 months after admission
T2 hyperintensity in the central pons and diffusely throughout the white matter of both hemispheres. The putamen, caudate nuclei, and thalami also involved.
T1-hypointense and T2-hyperintens central pons lesion without mass effect
T2-hyperintense lesions in the central pons
MRI findings
Table 1 Overview of the available case reports of CPM in context with eating disorders. ADL, activities of daily living; MRI, magnetic resonance imaging; n.a., not applicable.
Able to walk after 2 months, speech restored months later
Good motor recovery within 2 months
3 months later: slight dysarthria, mild cognitive dysfunction
MRI normalization 6 months after admission
n.a.
Slowly improving, still requiring assistance for all ADL after 6 weeks, independent for ADL after 7 months
Gradual clinical improvement
n.a.
Follow-up
T. Vladimirov, et al.
Clinical Neurology and Neurosurgery 192 (2020) 105722
Clinical Neurology and Neurosurgery 192 (2020) 105722
T. Vladimirov, et al.
Funding
[3] R.D. Adams, M. Victor, E.L. Mancall, Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients, AMA Arch. Neurol. Psychiatry 81 (1959) 154–172. [4] N. Bando, K. Watanabe, M. Tomotake, T. Taniguchi, T. Ohmori, Central pontine myelinolysis associated with a hypoglycemic coma in anorexia nervosa, Gen. Hosp. Psychiatry 27 (2005) 372–374. [5] B. Amann, M. Schäfer, A. Sterr, S. Arnold, H. Grunze, Central pontine myelinolysis in a patient with anorexia nervosa, Int. J. Eat. Disord. 30 (2001) 462–466. [6] T.L. Steckler, Central pontine myelinolysis in a patient with bulimia, South. Med. J. 88 (1995) 858–859. [7] C. Singer, D. Lorenzo, S. Papapetropoulos, A. Mesa, B. Bowen, Pontine/extrapontine myelinolysis occurring in the setting of an eating disorder, Neurology 64 (2005) 2156–2157. [8] T. Sugimoto, T. Murata, M. Omori, Y. Wada, Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa, J. Neurol. Neurosurg. Psychiatry 74 (2003) 353–355. [9] W.M. Greenberg, P.J. Shab, M. Vakharia, Anorexia nervosa/bulimia and central pontine myelinolysis, Gen. Hosp. Psychiatry 14 (1992) 357–358.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Competing Interest None. References [1] A.S. Patel, L. Matthews, W. Bruce-Jones, Central pontine myelinolysis as a complication of refeeding syndrome in a patient with anorexia nervosa, J. Neuropsychiatry Clin. Neurosci. 20 (2008) 371–373. [2] P.M. Copeland, Diuretic abuse and central pontine myelinolysis, J. Psychother. Psychosomatics 52 (1989) 101–105.
4