JNS-13222; No of Pages 2 Journal of the Neurological Sciences xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Central pontine myelinolysis without electrolyte disorder, alcoholism or denutrition
To the Editor We present the case of a 45 year-old woman, with a medical history of carcinoma of the cervix, thyroid nodules, renal angiomyolipoma, lumbago, anxiety and depression, and presenting a homozygous alphathalassemia. She didn't have a history of alcoholism, or malnutrition. She first presented to the emergency room for vertigo with nausea that evolved for one week. She was released the same day with an oral acetyl-leucine treatment. Laboratory tests and serum electrolytes were normal. Three days later, she came back to the emergency room because of persistent dizziness making sitting, standing and walking impossible. She also complained of severe headache and vomiting. Examination on admission in the neurology unit noted psychomotor slowing, complete paralysis of eye movements in lateral gaze to the right and to the left, binocular diplopia. Jerk reflexes were brisk, she complained of peri-oral and both hand paresthesia. There was no sensory-motor deficit. Lancaster test found ophthalmoplegia, bilateral paralysis of mainly abduction but also adduction. Cranial CT scanner was normal. Brain MRI noted a centro-pontine high signal intensity lesion in T2 weighted, fluid attenuated inversion recovery (Flair) and diffusion weighted sequences, appearing in low signal in T1 weighted sequences. On the apparent diffusion coefficient mapping, high signal was noted, indicating a vasogenic edema. These findings were typical of a centro-pontine myelinolysis. The laboratory tests on admission showed normal serum electrolytes, without any hyponatremia, hypernatremia, hypokalemia, hypophosphoremia, and hypomagnesemia. Renal function and liver function tests were within the normal range. Vitamins B12, B1, and B6, and albumin levels were normal. Blood cell count was normal except from low mean corpuscular volume (68 μm3) related to her alpha thalassemia. All immune tests were negative. Cerebrospinal fluid was normal. A thoracic-abdominal and -pelvic CT scan didn't find any argument for a neoplastic condition. She had thyroid nodules of a benign aspect on ultrasound which had not been punctured, and thyroid function tests were normal. Intravenous treatment with methyl-prednisolone (1 g/day during 5 days) was introduced, resulting first in an improvement in standing and walking, then in oculomotor function. Six months later, she only complained of rare headaches. The MRI lesion remained stable.
demyelination. Its pathophysiology is still poorly understood: not only osmotic mechanisms, but also complex immunologic, auto-immune, and ischemic hypotheses have been developed [1,2]. Hyponatremia would be a potent risk factor to CPM, and rapid sodium replacement has been implicated as one on the principal stimuli to glial damage. The prevailing hypothesis to explain CPM implicates reduced adaptive capacity of neuroglia to large shifts in serum osmolality. But most patients receiving even rapid sodium correction do not develop CPM. A background predisposition thus appears central to the development of this condition. Chronic alcohol abuse and liver transplantation (with use of cyclosporine) appear to be particular risk factors. Other risk factors have been described: liver dysfunction, adrenal insufficiency, malnutrition, chronic renal failure and hemodialysis, sepsis, and malignancy [2]. With more than one predisposing factor, CPM could develop in the absence of serum sodium fluctuations. (See Fig. 1.) Ashrafian suggests that individuals predisposed to CPM have inadequate glial cell energy provision that results in a pro-apoptotic drive, which renders them susceptible to glial injury from diverse causes [2]. In CPM, the precipitant of brain injury would be, most of the time, osmotic stress. Cases have been also described, with hypernatremia,
1. Discussion Our case is original because we could not find any of the causes or contributing factors usually encountered in this condition: no malnutrition or alcoholism, no electrolyte disorder, and no organ dysfunction. Centropontine myelinolysis (CPM) corresponds to a massive pontine
Fig. 1. Axial flair (fluid attenuated inversion recovery) brain MRI sequence showing hyperintensity signal of the pon characteristic of central pontine myelinolysis.
http://dx.doi.org/10.1016/j.jns.2014.05.045 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: Landais A, Central pontine myelinolysis without electrolyte disorder, alcoholism or denutrition, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.045
2
Letter to the Editor
hypokalemia, hypophosphoremia, and hypomagnesemia. Our case is interesting because of the lack of any risk factor or osmotic stress. It confirms, however, the hypothesis that iatrogenic sodium restoration may not be in all cases the mechanism of CPM and that normal admission sodium levels do not exclude this diagnosis. Clinical presentation of CPM may vary from coma, disorder of consciousness, tetraparesis, locked-in syndrome, pseudobulbar signs, movement disorders, to psychiatric manifestations or mild oculomotor symptoms such as horizontal gaze evoked nystagmus or incomplete abducens palsy. Asymptomatic cases with only imagery lesions have also been reported. Given the low prevalence of this condition, there are no randomized studies comparing the various treatments tested in this indication. Treatment is essentially preventive by careful correction of hyponatremia when it exists. In any case, symptomatic treatment should be initiated, fighting against recognized aggravating factors: hypoxia, hypokalemia, and vitamin deficiency. A stay in intensive care may be necessary. Treatment with steroid bolus, intravenous immunoglobulin, intravenous TRH or plasma exchange has also been tried. Hagiwara reported complete remission of neurological symptoms after treatment with steroid bolus (2 courses of 1 g/day of methylprednisolone for 3 days, at 1 week intervals) followed by 30 mg/day of oral prednisone, with a progressive decrease of dosage [3]. The author suggested an unknown immunological pathogenetic mechanism causing myelinolysis in CPM. A direct toxic mechanism of alcohol has also been invoked by analogy
with Marchiafava Bignami disease affecting the same field of chronic alcoholism and causing demyelination of the corpus callosum probably of direct toxic origin. The exact mechanism of this selective process of demyelinization remains obscure.
Conflict of interest None.
References [1] Norenberg MD. Central pontine myelinolysis: historical and mechanistic considerations. Metab Brain Dis 2010;25:97–106. [2] Ashrafian H, Davey P. A review of the causes of central pontine myelinosis: yet another apoptotic illness? Eur J Neurol 2001 Mar;8(2):103–9. [3] Hagiwara K, Okada Y, Shida N, Yamashita Y. Extensive central and extrapontine myelinolysis in a case of chronic alcoholism without hyponatremia: a case report with analysis of serial MR findings. Int Med 2008;47:431–5.
Anne Landais CHU de POINTE-A-PITRE, France 22 February 2014 Available online xxxx
Please cite this article as: Landais A, Central pontine myelinolysis without electrolyte disorder, alcoholism or denutrition, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.045
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Central pontine myelinolysis without electrolyte disorder, alcoholism or denutrition
To the Editor We present the case of a 45 year-old woman, with a medical history of carcinoma of the cervix, thyroid nodules, renal angiomyolipoma, lumbago, anxiety and depression, and presenting a homozygous alphathalassemia. She didn't have a history of alcoholism, or malnutrition. She first presented to the emergency room for vertigo with nausea that evolved for one week. She was released the same day with an oral acetyl-leucine treatment. Laboratory tests and serum electrolytes were normal. Three days later, she came back to the emergency room because of persistent dizziness making sitting, standing and walking impossible. She also complained of severe headache and vomiting. Examination on admission in the neurology unit noted psychomotor slowing, complete paralysis of eye movements in lateral gaze to the right and to the left, binocular diplopia. Jerk reflexes were brisk, she complained of peri-oral and both hand paresthesia. There was no sensory-motor deficit. Lancaster test found ophthalmoplegia, bilateral paralysis of mainly abduction but also adduction. Cranial CT scanner was normal. Brain MRI noted a centro-pontine high signal intensity lesion in T2 weighted, fluid attenuated inversion recovery (Flair) and diffusion weighted sequences, appearing in low signal in T1 weighted sequences. On the apparent diffusion coefficient mapping, high signal was noted, indicating a vasogenic edema. These findings were typical of a centro-pontine myelinolysis. The laboratory tests on admission showed normal serum electrolytes, without any hyponatremia, hypernatremia, hypokalemia, hypophosphoremia, and hypomagnesemia. Renal function and liver function tests were within the normal range. Vitamins B12, B1, and B6, and albumin levels were normal. Blood cell count was normal except from low mean corpuscular volume (68 μm3) related to her alpha thalassemia. All immune tests were negative. Cerebrospinal fluid was normal. A thoracic-abdominal and -pelvic CT scan didn't find any argument for a neoplastic condition. She had thyroid nodules of a benign aspect on ultrasound which had not been punctured, and thyroid function tests were normal. Intravenous treatment with methyl-prednisolone (1 g/day during 5 days) was introduced, resulting first in an improvement in standing and walking, then in oculomotor function. Six months later, she only complained of rare headaches. The MRI lesion remained stable.
demyelination. Its pathophysiology is still poorly understood: not only osmotic mechanisms, but also complex immunologic, auto-immune, and ischemic hypotheses have been developed [1,2]. Hyponatremia would be a potent risk factor to CPM, and rapid sodium replacement has been implicated as one on the principal stimuli to glial damage. The prevailing hypothesis to explain CPM implicates reduced adaptive capacity of neuroglia to large shifts in serum osmolality. But most patients receiving even rapid sodium correction do not develop CPM. A background predisposition thus appears central to the development of this condition. Chronic alcohol abuse and liver transplantation (with use of cyclosporine) appear to be particular risk factors. Other risk factors have been described: liver dysfunction, adrenal insufficiency, malnutrition, chronic renal failure and hemodialysis, sepsis, and malignancy [2]. With more than one predisposing factor, CPM could develop in the absence of serum sodium fluctuations. (See Fig. 1.) Ashrafian suggests that individuals predisposed to CPM have inadequate glial cell energy provision that results in a pro-apoptotic drive, which renders them susceptible to glial injury from diverse causes [2]. In CPM, the precipitant of brain injury would be, most of the time, osmotic stress. Cases have been also described, with hypernatremia,
1. Discussion Our case is original because we could not find any of the causes or contributing factors usually encountered in this condition: no malnutrition or alcoholism, no electrolyte disorder, and no organ dysfunction. Centropontine myelinolysis (CPM) corresponds to a massive pontine
Fig. 1. Axial flair (fluid attenuated inversion recovery) brain MRI sequence showing hyperintensity signal of the pon characteristic of central pontine myelinolysis.
http://dx.doi.org/10.1016/j.jns.2014.05.045 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: Landais A, Central pontine myelinolysis without electrolyte disorder, alcoholism or denutrition, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.045
2
Letter to the Editor
hypokalemia, hypophosphoremia, and hypomagnesemia. Our case is interesting because of the lack of any risk factor or osmotic stress. It confirms, however, the hypothesis that iatrogenic sodium restoration may not be in all cases the mechanism of CPM and that normal admission sodium levels do not exclude this diagnosis. Clinical presentation of CPM may vary from coma, disorder of consciousness, tetraparesis, locked-in syndrome, pseudobulbar signs, movement disorders, to psychiatric manifestations or mild oculomotor symptoms such as horizontal gaze evoked nystagmus or incomplete abducens palsy. Asymptomatic cases with only imagery lesions have also been reported. Given the low prevalence of this condition, there are no randomized studies comparing the various treatments tested in this indication. Treatment is essentially preventive by careful correction of hyponatremia when it exists. In any case, symptomatic treatment should be initiated, fighting against recognized aggravating factors: hypoxia, hypokalemia, and vitamin deficiency. A stay in intensive care may be necessary. Treatment with steroid bolus, intravenous immunoglobulin, intravenous TRH or plasma exchange has also been tried. Hagiwara reported complete remission of neurological symptoms after treatment with steroid bolus (2 courses of 1 g/day of methylprednisolone for 3 days, at 1 week intervals) followed by 30 mg/day of oral prednisone, with a progressive decrease of dosage [3]. The author suggested an unknown immunological pathogenetic mechanism causing myelinolysis in CPM. A direct toxic mechanism of alcohol has also been invoked by analogy
with Marchiafava Bignami disease affecting the same field of chronic alcoholism and causing demyelination of the corpus callosum probably of direct toxic origin. The exact mechanism of this selective process of demyelinization remains obscure.
Conflict of interest None.
References [1] Norenberg MD. Central pontine myelinolysis: historical and mechanistic considerations. Metab Brain Dis 2010;25:97–106. [2] Ashrafian H, Davey P. A review of the causes of central pontine myelinosis: yet another apoptotic illness? Eur J Neurol 2001 Mar;8(2):103–9. [3] Hagiwara K, Okada Y, Shida N, Yamashita Y. Extensive central and extrapontine myelinolysis in a case of chronic alcoholism without hyponatremia: a case report with analysis of serial MR findings. Int Med 2008;47:431–5.
Anne Landais CHU de POINTE-A-PITRE, France 22 February 2014 Available online xxxx
Please cite this article as: Landais A, Central pontine myelinolysis without electrolyte disorder, alcoholism or denutrition, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.045
