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Recurrent facial dyskinesias due to extrapontine myelinolysis
Parkinsonism and Related Disorders 19 (2013) 385–387
Contents lists available at SciVerse ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Recurrent facial dyskinesias due to extrapontine myelinolysis Keywords: Osmotic demyelination syndrome Extrapontine myelinolysis Facial dyskinesia
Osmotic demyelination syndrome (ODS) of the central nervous system is a rare condition related to rapid osmotic changes, particularly an aggressive correction of hyponatremia and severe or prolonged hypo-osmotic states [1]. Alcohol abuse and liver failure are important risk factors, even with little osmotic shifts [1]. ODS includes two variants: central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) [1,2]. The former, and the most frequent, involves the basis pontis; the latter can be found in the cerebellum, lateral geniculate body, basal ganglia, and cerebral white matter. Rarely, EPM can manifest with movement disorders: parkinsonism is common, while involuntary movements such as myoclonus, choreoathetosis and dystonia are less frequent [1,2]. Neuropathological hallmarks are glial apoptosis with dissolution of the myelin sheaths and sparing of neuronal axons without inflammation. Neuroradiology plays a central role in the diagnosis of ODS. Brain MRI shows areas of signal hyperintensity on T2-weighted, FLAIR and DWI images. As for CPM, these signal alterations involve the central pons (with a typical “trident” or “butterfly” shape), whereas in EPM they are usually described in the cerebellum, thalamus, basal ganglia (lenticular nuclei and caudate) and subcortical white matter. Clinical and neuroradiological findings may have a spontaneous regression due to remyelination processes. A deficient or ineffective remyelination might be responsible for the delayed onset of new symptoms, particularly when EPM involves the basal ganglia [3]. Differing from acute myelinolysis that is usually reversible, late onset or recurrent symptoms due to a deficient and altered remyelination are often permanent, evolve with time, and may be a therapeutic challenge. Here we describe a case of EPM involving basal ganglia and cerebellum that presented with focal oro-bucco-lingual dyskinesias and ataxia. While ataxia showed a persistent temporal pattern, facial dyskinesias recurred three months after spontaneous remission of a first presentation. We report on a 63 year-old man with a past medical history remarkable for alcohol-related liver cirrhosis complicated by frequent episodes of liver failure, ascitis and electrolytes imbalance. During one of these events, three months earlier, a severe hyponatremia (122 mEq/L) was detected and slowly corrected with saline infusion at a speed of 1 mEq/hr. Very mild oro-bucco-lingual dyskinesia and unsteady gait appeared within the second week after 1353-8020/$ – see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.parkreldis.2012.07.014
correction of hyponatremia. Facial dyskinesias had a spontaneous remission within 10 days, while the gait disorder did not improve. Three months later, the patient was again admitted to the hospital because of acute development of pervasive oro-bucco-lingual and neck dyskinesias causing dysarthria and dysphagia. In the period preceding the first dyskinetic event, and in the following three months, the patient was not on psychoactive or antiemetic medications. Upon current admission, neurological examination showed an ataxic gait, wide based and reeling, without Romberg’s sign. Ample, brusque dyskinesias were localized to the oro-buccolingual and cephalic regions with side to side shaking of the head, lip pursing, pouting, mouth opening, and facial grimacing. The involuntary movements were more severe than those recorded three months earlier and also involved the neck. These movements consistently impaired the patient’s ability to eat and drink. The patient was also unable to communicate because of frequent speech arrests due to the severe involuntary movements of the tongue. Deep tendon reflexes, strength, and coordination were normal. Sensory examination, with testing of touch, vibration and joint position sensations, was within normal limits. In particular, no signs of motor or sensory polyneuropathy were detectable. Cranial nerves were unremarkable; there wasn’t evidence of nystagmus or eye movement abnormalities. A brain CT scan showed diffuse mild atrophy and chronic cerebrovascular disease. Blood investigations showed mild hyponatremia (129 mEq/L), which was slowly corrected with saline solution a few days after admission. Serum and urine copper and ceruloplasmin levels were within normal limits; on slit-lamp examination there was no evidence of Kayser-Fleischer ring. Peripheral blood smears were negative for acanthocytes. Four days after admission, a brain MRI scan showed T2-hyperintense bilateral symmetric lesions in the pallidum, putamen, cerebellar middle peduncles and white matter (Fig. 1), without concomitant alteration in the pons, consistent with EPM. MRI did not reveal T1-hyperintensity in the pallidum, typically present in hepatic encephalopathy, or T2 signal alterations in the midbrain (“face of the giant panda” sign) characteristic of Wilson’s disease, nor any lesion in the pons that might have caused wallerian degeneration of the cerebellar peduncles. The patient was started on haloperidol with clinical benefit. Two months later, the patient died of liver failure.
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Letter to the Editor / Parkinsonism and Related Disorders 19 (2013) 385–387
Fig. 1. Brain MRI: coronal (a,b) and axial (c,d) T2-weighted images showing symmetric hyperintense lesions at the level of the cerebellar peduncle and cerebellar white matter (open arrowheads) and at the level of the pallidum (grey arrowheads) and putamen (short arrows) consistent with extrapontine myelinolysis.
The present case describes facial dyskinesias in a patient with liver cirrhosis, hyponatremia and EPM affecting bilaterally the basal ganglia. To our knowledge no other cases of focal facial and neck dyskinesias secondary to EPM have been described in the literature, while only one previous case of focal orolingual dyskinesias is reported as a consequence of CPM [4]. Although facial dyskinesias is a rare manifestation of EPM, this condition needs to be considered since it may set diagnostic challenges with tardive dyskinesia and other more frequent choreic syndromes. Among neurological diseases leading to dyskinesia, those associated with liver cirrhosis, such as acquired and hereditary hepato-cerebral degeneration, represent diagnostic alternatives to EPM that may require a thorough diagnostic work-up. In this context, the type and the extension of MRI alterations can offer important information since both hepatic encephalopathy and Wilson’s disease have typical neuroradiological signatures that were not present in the case described here. Myelinolysis occurs especially where white and grey matter are embedded together, like in the basal ganglia [1]. In acute myelinolysis, both symptoms and MRI changes usually occur between 7 and 14 days after the osmotic shift [2]. Subsequent slow remyelination process results from budding and branching of nearby glial cells. The progressive mending of myelin damage is clinically expressed by a gradual remission of signs and symptoms over weeks or
months; this process, however, can be ineffective. The ongoing remyelination can alter physiological connections between cells, thus modifying their network of signalling [3]. The result of this haphazard reorganization of myelin structures is represented by the onset of signs and symptoms usually at months’ distance from the primary damage; these can vary from the first clinical picture and even be totally dissimilar [5]. An ineffective remyelination is more frequent in the basal ganglia and is the cause of recurrent or delayed extrapyramidal signs [3,5]. In our patient we hypothesized that the recurrence of facial dyskinesias, months after the first episode, may reflect this ineffective remyelination. Although the demonstration of EPM by MRI study during the first episode of facial dyskinesias is lacking, the patient’s history may be considered as an example of both acute and delayed expression of ODS. In fact, he had a first episode of dyskinesias some months earlier, along with a severe hyponatremic condition. It is possible that the swift osmotic stress led to EPM with the first acute and transient choreic movements and the onset of ataxia. The delayed onset of facial dyskinesias three months later could be related to a deficient or ineffective chronic remyelination. Alternatively, mild hyponatremia could be responsible for the occurrence of facial dyskinesias since basal ganglia were made more vulnerable to ODS by a previous severe hyponatremic insult.
Letter to the Editor / Parkinsonism and Related Disorders 19 (2013) 385–387
In summary, we presented a case of recurrent facial dyskinesia due to basal ganglia EPM and discussed the possible role of ineffective remyelination in the recurrence of these symptoms. We suggest isolated focal facial and neck dyskinesia as a new and so far not yet described symptom of myelinolysis of the basal ganglia. This case highlights the importance of EPM as a diagnostic hypothesis when considering the onset of focal hyperkinetic movements in a cirrhotic and/or hyponatremic patient. Financial disclosure The work was supported by research funding of the Department of Neurosciences, University of Padova. All the Authors declare no conflict of interest related to the research covered by the manuscript. A Cagnin has served as consultant in Advisory Board for Novartis and received honoraria from Novartis and Lundbeck.
387
[3] Seah ABH, Chan LL, Wong MC, Tan EK. Evolving spectrum of movement disorders in extrapontine and central pontine myelinolysis. Parkinsonism Relat Disord 2002;9:117–9. [4] Chu NS. Orolingual dyskinesia in central pontine myelinolysis. Acta Neurol Taiwan 2004;13:156–7. [5] Roggendorf J, Burghaus L, Liu WC, Weisenbach S, Eggers C, Fink GR, et al. Belly dancer’s syndrome following central pontine and extrapontine myelinolysis. Mov Disord 2007;22:892–4.
Silvia Favaretto, Renzo Manara Department of Neurosciences: Science NPSRR, University Hospital of Padua, Via Giustiniani 5, 35128 Padua, Italy Marco Senzolo Department of Surgical, Oncological and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy Annachiara Cagnin*,1 I.R.C.C.S. San Camillo Hospital Foundation, Via Alberoni, 70, 30126 – Venice, Italy * Corresponding author. Tel.: þ39 049 8213601; fax: þ39 049 8751770. E-mail address: [email protected]
References [1] Kumar S, Fowler M, Gonzalez-Toledo E, Jaffe SL. Central pontine myelinolysis, an update. Neurol Res 2006;28:360–6. [2] Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry 2004;75(S3):22–8.
16 May 2012
1
On leave to I.R.C.C.S., San Camillo Hospital Foundation, Venice, Italy.
Contents lists available at SciVerse ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Recurrent facial dyskinesias due to extrapontine myelinolysis Keywords: Osmotic demyelination syndrome Extrapontine myelinolysis Facial dyskinesia
Osmotic demyelination syndrome (ODS) of the central nervous system is a rare condition related to rapid osmotic changes, particularly an aggressive correction of hyponatremia and severe or prolonged hypo-osmotic states [1]. Alcohol abuse and liver failure are important risk factors, even with little osmotic shifts [1]. ODS includes two variants: central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) [1,2]. The former, and the most frequent, involves the basis pontis; the latter can be found in the cerebellum, lateral geniculate body, basal ganglia, and cerebral white matter. Rarely, EPM can manifest with movement disorders: parkinsonism is common, while involuntary movements such as myoclonus, choreoathetosis and dystonia are less frequent [1,2]. Neuropathological hallmarks are glial apoptosis with dissolution of the myelin sheaths and sparing of neuronal axons without inflammation. Neuroradiology plays a central role in the diagnosis of ODS. Brain MRI shows areas of signal hyperintensity on T2-weighted, FLAIR and DWI images. As for CPM, these signal alterations involve the central pons (with a typical “trident” or “butterfly” shape), whereas in EPM they are usually described in the cerebellum, thalamus, basal ganglia (lenticular nuclei and caudate) and subcortical white matter. Clinical and neuroradiological findings may have a spontaneous regression due to remyelination processes. A deficient or ineffective remyelination might be responsible for the delayed onset of new symptoms, particularly when EPM involves the basal ganglia [3]. Differing from acute myelinolysis that is usually reversible, late onset or recurrent symptoms due to a deficient and altered remyelination are often permanent, evolve with time, and may be a therapeutic challenge. Here we describe a case of EPM involving basal ganglia and cerebellum that presented with focal oro-bucco-lingual dyskinesias and ataxia. While ataxia showed a persistent temporal pattern, facial dyskinesias recurred three months after spontaneous remission of a first presentation. We report on a 63 year-old man with a past medical history remarkable for alcohol-related liver cirrhosis complicated by frequent episodes of liver failure, ascitis and electrolytes imbalance. During one of these events, three months earlier, a severe hyponatremia (122 mEq/L) was detected and slowly corrected with saline infusion at a speed of 1 mEq/hr. Very mild oro-bucco-lingual dyskinesia and unsteady gait appeared within the second week after 1353-8020/$ – see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.parkreldis.2012.07.014
correction of hyponatremia. Facial dyskinesias had a spontaneous remission within 10 days, while the gait disorder did not improve. Three months later, the patient was again admitted to the hospital because of acute development of pervasive oro-bucco-lingual and neck dyskinesias causing dysarthria and dysphagia. In the period preceding the first dyskinetic event, and in the following three months, the patient was not on psychoactive or antiemetic medications. Upon current admission, neurological examination showed an ataxic gait, wide based and reeling, without Romberg’s sign. Ample, brusque dyskinesias were localized to the oro-buccolingual and cephalic regions with side to side shaking of the head, lip pursing, pouting, mouth opening, and facial grimacing. The involuntary movements were more severe than those recorded three months earlier and also involved the neck. These movements consistently impaired the patient’s ability to eat and drink. The patient was also unable to communicate because of frequent speech arrests due to the severe involuntary movements of the tongue. Deep tendon reflexes, strength, and coordination were normal. Sensory examination, with testing of touch, vibration and joint position sensations, was within normal limits. In particular, no signs of motor or sensory polyneuropathy were detectable. Cranial nerves were unremarkable; there wasn’t evidence of nystagmus or eye movement abnormalities. A brain CT scan showed diffuse mild atrophy and chronic cerebrovascular disease. Blood investigations showed mild hyponatremia (129 mEq/L), which was slowly corrected with saline solution a few days after admission. Serum and urine copper and ceruloplasmin levels were within normal limits; on slit-lamp examination there was no evidence of Kayser-Fleischer ring. Peripheral blood smears were negative for acanthocytes. Four days after admission, a brain MRI scan showed T2-hyperintense bilateral symmetric lesions in the pallidum, putamen, cerebellar middle peduncles and white matter (Fig. 1), without concomitant alteration in the pons, consistent with EPM. MRI did not reveal T1-hyperintensity in the pallidum, typically present in hepatic encephalopathy, or T2 signal alterations in the midbrain (“face of the giant panda” sign) characteristic of Wilson’s disease, nor any lesion in the pons that might have caused wallerian degeneration of the cerebellar peduncles. The patient was started on haloperidol with clinical benefit. Two months later, the patient died of liver failure.
386
Letter to the Editor / Parkinsonism and Related Disorders 19 (2013) 385–387
Fig. 1. Brain MRI: coronal (a,b) and axial (c,d) T2-weighted images showing symmetric hyperintense lesions at the level of the cerebellar peduncle and cerebellar white matter (open arrowheads) and at the level of the pallidum (grey arrowheads) and putamen (short arrows) consistent with extrapontine myelinolysis.
The present case describes facial dyskinesias in a patient with liver cirrhosis, hyponatremia and EPM affecting bilaterally the basal ganglia. To our knowledge no other cases of focal facial and neck dyskinesias secondary to EPM have been described in the literature, while only one previous case of focal orolingual dyskinesias is reported as a consequence of CPM [4]. Although facial dyskinesias is a rare manifestation of EPM, this condition needs to be considered since it may set diagnostic challenges with tardive dyskinesia and other more frequent choreic syndromes. Among neurological diseases leading to dyskinesia, those associated with liver cirrhosis, such as acquired and hereditary hepato-cerebral degeneration, represent diagnostic alternatives to EPM that may require a thorough diagnostic work-up. In this context, the type and the extension of MRI alterations can offer important information since both hepatic encephalopathy and Wilson’s disease have typical neuroradiological signatures that were not present in the case described here. Myelinolysis occurs especially where white and grey matter are embedded together, like in the basal ganglia [1]. In acute myelinolysis, both symptoms and MRI changes usually occur between 7 and 14 days after the osmotic shift [2]. Subsequent slow remyelination process results from budding and branching of nearby glial cells. The progressive mending of myelin damage is clinically expressed by a gradual remission of signs and symptoms over weeks or
months; this process, however, can be ineffective. The ongoing remyelination can alter physiological connections between cells, thus modifying their network of signalling [3]. The result of this haphazard reorganization of myelin structures is represented by the onset of signs and symptoms usually at months’ distance from the primary damage; these can vary from the first clinical picture and even be totally dissimilar [5]. An ineffective remyelination is more frequent in the basal ganglia and is the cause of recurrent or delayed extrapyramidal signs [3,5]. In our patient we hypothesized that the recurrence of facial dyskinesias, months after the first episode, may reflect this ineffective remyelination. Although the demonstration of EPM by MRI study during the first episode of facial dyskinesias is lacking, the patient’s history may be considered as an example of both acute and delayed expression of ODS. In fact, he had a first episode of dyskinesias some months earlier, along with a severe hyponatremic condition. It is possible that the swift osmotic stress led to EPM with the first acute and transient choreic movements and the onset of ataxia. The delayed onset of facial dyskinesias three months later could be related to a deficient or ineffective chronic remyelination. Alternatively, mild hyponatremia could be responsible for the occurrence of facial dyskinesias since basal ganglia were made more vulnerable to ODS by a previous severe hyponatremic insult.
Letter to the Editor / Parkinsonism and Related Disorders 19 (2013) 385–387
In summary, we presented a case of recurrent facial dyskinesia due to basal ganglia EPM and discussed the possible role of ineffective remyelination in the recurrence of these symptoms. We suggest isolated focal facial and neck dyskinesia as a new and so far not yet described symptom of myelinolysis of the basal ganglia. This case highlights the importance of EPM as a diagnostic hypothesis when considering the onset of focal hyperkinetic movements in a cirrhotic and/or hyponatremic patient. Financial disclosure The work was supported by research funding of the Department of Neurosciences, University of Padova. All the Authors declare no conflict of interest related to the research covered by the manuscript. A Cagnin has served as consultant in Advisory Board for Novartis and received honoraria from Novartis and Lundbeck.
387
[3] Seah ABH, Chan LL, Wong MC, Tan EK. Evolving spectrum of movement disorders in extrapontine and central pontine myelinolysis. Parkinsonism Relat Disord 2002;9:117–9. [4] Chu NS. Orolingual dyskinesia in central pontine myelinolysis. Acta Neurol Taiwan 2004;13:156–7. [5] Roggendorf J, Burghaus L, Liu WC, Weisenbach S, Eggers C, Fink GR, et al. Belly dancer’s syndrome following central pontine and extrapontine myelinolysis. Mov Disord 2007;22:892–4.
Silvia Favaretto, Renzo Manara Department of Neurosciences: Science NPSRR, University Hospital of Padua, Via Giustiniani 5, 35128 Padua, Italy Marco Senzolo Department of Surgical, Oncological and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy Annachiara Cagnin*,1 I.R.C.C.S. San Camillo Hospital Foundation, Via Alberoni, 70, 30126 – Venice, Italy * Corresponding author. Tel.: þ39 049 8213601; fax: þ39 049 8751770. E-mail address: [email protected]
References [1] Kumar S, Fowler M, Gonzalez-Toledo E, Jaffe SL. Central pontine myelinolysis, an update. Neurol Res 2006;28:360–6. [2] Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry 2004;75(S3):22–8.
16 May 2012
1
On leave to I.R.C.C.S., San Camillo Hospital Foundation, Venice, Italy.