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Myopathic camptocormia associated with myasthenia gravis
Clinical Neurology and Neurosurgery 115 (2013) 1488–1489
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Myopathic camptocormia associated with myasthenia gravis Perrine Devic a,b,∗ , Ariane Choumert c , Sandra Vukusic b , Christian Confavreux b , Philippe Petiot a a
Université Lyon I, Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Centre de Référence Maladies Neuromusculaires, Lyon, France Université Lyon I, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie A, Lyon, France c Université Lyon I, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Lyon, France b
a r t i c l e
i n f o
Article history: Received 4 September 2012 Received in revised form 18 November 2012 Accepted 19 November 2012 Available online 21 December 2012 Keywords: Camptocormia Myasthenia gravis Myopathy
1. Introduction Camptocormia is characterized by an involuntary forward flexed posture of the thoracolumbar spine. It can be observed in numerous conditions including rheumatologic diseases, Parkinson disease, inflammatory myopathies, facio-scapulo-humeral muscular dystrophy, myotonic dystrophy, motor neuron disease or myasthenia gravis (MG) [1]. In the latter, camptocormia is usually related to a paraspinal muscle weakness secondary to the neuromuscular junction dysfunction and often resolves with acetylcholinesterase inhibitors or immunosuppressive treatments [2,3]. Myopathic changes of paraspinal muscles have only been reported once in MG-associated camptocormia [4]. Here, we report one patient with thymoma and generalized MG who presented isolated camptocormia unresponsive to either cholinesterase inhibitors or immunosuppressant treatments. 2. Case report A 38-year-old male, without any medical family history, had undergone surgery for a lymphoepithelial thymoma at the age of 15 years with a complete resection not requiring chemotherapy nor radiotherapy. At the age of 24, he developed generalized
∗ Corresponding author at: Hôpital de la Croix Rousse, Neurologie Explorations Fonctionnelles, Centre de Référence des Maladies Neuromusculaires, 93, Grande Rue de la Croix Rousse, 69319 Lyon Cedex 4, France. Tel.: +33 47071866; fax: +33 472071867. E-mail address: [email protected] (P. Devic). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.11.015
MG with proximal weakness followed by oculo-bulbar involvement. Anti-acetylcholine Receptor (AChR) antibodies were highly positive (94 nm/L, positive value above 0.5 nmol/L) and repetitive stimulations of spinal, radial and axillary nerves demonstrated a significant decrement (from 30 to 60%). Prednisolone (1.5 mg/kg per day) plus azathioprine (2.5 mg/kg per day) were started at the age of 27 due to poor control of the disease despite pyridostigmine 1200 mg per day. This therapeutic regimen initially allowed a fair control of the disease and a drastic reduction of cholinesterase inhibitors dosage to 120 mg per day. Steroids were progressively decreased and stopped at the age of 36 according to the patient’s wishes. Unfortunately, this led to the recurrence of fatiguability, dysphagia, diplopia and ptosis which were dealt with the substitution of azathioprine by mycophenolate mofetil (25 mg/kg per day) and one infusion of intravenous immunoglobulin (2 g/kg during five days). This second line therapy allowed complete resolution of his myasthenic symptoms. Two years later, the patient developed a progressive and stable bent spine syndrome though former symptoms were still under control and the regimen of mycophenolate mofetil unchanged. He had increased difficulty in keeping his head elevated. Neurologic examination showed weakness of dorsal paraspinal muscles and marked forward head drop. He could not straighten his back in spite of maximal effort and he had to support his chin with his hand to look forwards. Abnormal posture was increased while walking and disappeared only in the recumbent position. As mentioned, myasthenic symptoms were still under control and consisted in mild fatiguability when walking and intermittent ptosis in the evening. Repetitive stimulations showed a 30% decrement in the trapezius and genioglossus. Pyridostigmine (600 mg per day) or ephedronium test did not improve
P. Devic et al. / Clinical Neurology and Neurosurgery 115 (2013) 1488–1489
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Fig. 1. T1 weighted axial MRI images of lumbar (A) and thoracic (B) spine showing fatty atrophy of the paravertebral muscles.
the bent spine. Since the patient refused further steroid treatment, repetitive courses of immunoglobulin (2 g/kg during five days) were tried but left the patient’s symptoms unchanged. Needle electromyography (EMG) did not reveal any myopathic pattern or spontaneous activities in any muscles including upper and lower limb and T6–T10 paraspinal muscles. While all biological analyses (including erythrocyte sedimentation rate, thyroid function, blood cell count, pyruvate acid and lactate acid) were in normal range, creatine kinase levels were slightly increased (480 UI/L) and anti-AChR antibodies remained highly positive (92 nm/L). Whereas CT-scan of limb muscles was normal, MRI showed an isolated atrophy with major fatty replacement of the thoracolumbar and paraspinal muscles (Fig. 1). Spine MRI was normal. Because of severe paraspinal muscle atrophy, a deltoid biopsy was performed and this was normal. Thoracic CT revealed no thymomatous mass. The patient condition remained stable during a 3-year follow up. Mycophenolate mofetil was progressively withdrawn one year after the onset of camptocormia without any consequences. 3. Discussion We report the case of a patient with AChR antibody positive MG who presented with isolated myopathic camptocormia unresponsive to cholinesterase inhibitors and immunosuppressive treatments. Camptocormia can be associated with central or peripheral nervous system diseases which have been ruled out in this patient upon clinical evolution, EMG, muscle biopsy and spine MRI. Degenerative or idiopathic camptocormia is unlikely because it is extremely rare before the age of fifty. A steroid induced myopathy could be considered but does not fit with the selective involvement of paraspinal muscles and the lack of evocative histological signs on muscle biopsy such as lipid storage. A more diffuse myopathic process is unlikely in our patient’s case, because of the absence of a family history, the non-involvement of other muscles after 3 years of follow-up and no limb abnormalities were detected on limb muscle CT imaging, EMG or muscle biopsy. Camptocormia secondary to impaired neuromuscular transmission is unlikely in this patient’s case because he did not respond to pyridostigmine, edrophonium or further intravenous immunoglobulin treatment. Furthermore, camptocormia occured while the rest of the patient’s MG symptoms were in remission. Lastly, the withdrawal of mycophenolate did not result in worsening of the patient’s bent spine. Rodolico et al. previously
reported a case of a patient presenting with camptocormia associated with MG with myopathic changes involving cervico-thoracic muscles on EMG and MRI [4]. Similarly, the camptocormia did not respond to prednisolone nor to cholinesterase inhibitor. The authors hypothesized that the axial myopathy could be secondary to an inflammatory myopathy. However, if our patient’s camptocormia had been due to an inflammatory myopathy, then he would have been expected to respond to immunosuppressant treatments. Finally, a myopathic process with marked muscle wasting and fatty replacement is sometimes encountered in MG, specially in muscle-specific kinase (MuSK) antibody positive MG and in severe and chronic AChR antibody positive MG [5]. MG associated myopathic changes usually occur in MG with a very long evolution and previous high dose steroid treatment (>40 mg alternate day) [5]. Therefore, it is possible that the same myopathic process could have selectively involved the paraspinal muscles in our patient. Our case should raise the clinician’s awareness that in some patients MG can be associated with myopathic camptocormia which does not respond to anticholinesterase inhibitors nor to immunosuppressants. In this situation, the clinician should image the paraspinal muscles in search of a myopathic fatty degenerative process, and exclude a more diffuse myopathic process with other investigations such as limb muscle imaging. 4. Conclusion Clinicians should therefore be cautious when using potentially harmful immunosuppressive treatments in MG-associated camptocormia, where patients fail to respond to cholinesterase inhibitors and/or where investigations may demonstrate a more diffuse myopathic process, which is less likely to respond to treatment. References [1] Finsterer J, Strobl W. Presentation, etiology, diagnosis, and management of camptocormia. European Neurology 2010;64:1–8. [2] D’Amelio M, Di Benedetto N, Ragonese P, Daniele O, Brighina F, Fierro B, et al. Dropped head as an unusual presenting sign of myasthenia gravis. Neurological Sciences 2007;28:104–6. [3] Kataoka H, Kiriyama T, Ueno S. Myasthenia gravis can cause camptocormia. Journal of Neurology, Neurosurgery and Psychiatry 2012;83:469–70. [4] Rodolico C, Messina S, Toscano A, Vita G, Gaeta M. Axial myopathy in myasthenia: a misleading cause of dropped head. Muscle and Nerve 2004;29: 329–30. [5] Farrugia ME, Robson MD, Clover L, Anslow P, Newsom-Davis J, Kennett R, et al. MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis. Brain 2006;129:1481–92.
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Myopathic camptocormia associated with myasthenia gravis Perrine Devic a,b,∗ , Ariane Choumert c , Sandra Vukusic b , Christian Confavreux b , Philippe Petiot a a
Université Lyon I, Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Centre de Référence Maladies Neuromusculaires, Lyon, France Université Lyon I, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie A, Lyon, France c Université Lyon I, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Lyon, France b
a r t i c l e
i n f o
Article history: Received 4 September 2012 Received in revised form 18 November 2012 Accepted 19 November 2012 Available online 21 December 2012 Keywords: Camptocormia Myasthenia gravis Myopathy
1. Introduction Camptocormia is characterized by an involuntary forward flexed posture of the thoracolumbar spine. It can be observed in numerous conditions including rheumatologic diseases, Parkinson disease, inflammatory myopathies, facio-scapulo-humeral muscular dystrophy, myotonic dystrophy, motor neuron disease or myasthenia gravis (MG) [1]. In the latter, camptocormia is usually related to a paraspinal muscle weakness secondary to the neuromuscular junction dysfunction and often resolves with acetylcholinesterase inhibitors or immunosuppressive treatments [2,3]. Myopathic changes of paraspinal muscles have only been reported once in MG-associated camptocormia [4]. Here, we report one patient with thymoma and generalized MG who presented isolated camptocormia unresponsive to either cholinesterase inhibitors or immunosuppressant treatments. 2. Case report A 38-year-old male, without any medical family history, had undergone surgery for a lymphoepithelial thymoma at the age of 15 years with a complete resection not requiring chemotherapy nor radiotherapy. At the age of 24, he developed generalized
∗ Corresponding author at: Hôpital de la Croix Rousse, Neurologie Explorations Fonctionnelles, Centre de Référence des Maladies Neuromusculaires, 93, Grande Rue de la Croix Rousse, 69319 Lyon Cedex 4, France. Tel.: +33 47071866; fax: +33 472071867. E-mail address: [email protected] (P. Devic). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.11.015
MG with proximal weakness followed by oculo-bulbar involvement. Anti-acetylcholine Receptor (AChR) antibodies were highly positive (94 nm/L, positive value above 0.5 nmol/L) and repetitive stimulations of spinal, radial and axillary nerves demonstrated a significant decrement (from 30 to 60%). Prednisolone (1.5 mg/kg per day) plus azathioprine (2.5 mg/kg per day) were started at the age of 27 due to poor control of the disease despite pyridostigmine 1200 mg per day. This therapeutic regimen initially allowed a fair control of the disease and a drastic reduction of cholinesterase inhibitors dosage to 120 mg per day. Steroids were progressively decreased and stopped at the age of 36 according to the patient’s wishes. Unfortunately, this led to the recurrence of fatiguability, dysphagia, diplopia and ptosis which were dealt with the substitution of azathioprine by mycophenolate mofetil (25 mg/kg per day) and one infusion of intravenous immunoglobulin (2 g/kg during five days). This second line therapy allowed complete resolution of his myasthenic symptoms. Two years later, the patient developed a progressive and stable bent spine syndrome though former symptoms were still under control and the regimen of mycophenolate mofetil unchanged. He had increased difficulty in keeping his head elevated. Neurologic examination showed weakness of dorsal paraspinal muscles and marked forward head drop. He could not straighten his back in spite of maximal effort and he had to support his chin with his hand to look forwards. Abnormal posture was increased while walking and disappeared only in the recumbent position. As mentioned, myasthenic symptoms were still under control and consisted in mild fatiguability when walking and intermittent ptosis in the evening. Repetitive stimulations showed a 30% decrement in the trapezius and genioglossus. Pyridostigmine (600 mg per day) or ephedronium test did not improve
P. Devic et al. / Clinical Neurology and Neurosurgery 115 (2013) 1488–1489
1489
Fig. 1. T1 weighted axial MRI images of lumbar (A) and thoracic (B) spine showing fatty atrophy of the paravertebral muscles.
the bent spine. Since the patient refused further steroid treatment, repetitive courses of immunoglobulin (2 g/kg during five days) were tried but left the patient’s symptoms unchanged. Needle electromyography (EMG) did not reveal any myopathic pattern or spontaneous activities in any muscles including upper and lower limb and T6–T10 paraspinal muscles. While all biological analyses (including erythrocyte sedimentation rate, thyroid function, blood cell count, pyruvate acid and lactate acid) were in normal range, creatine kinase levels were slightly increased (480 UI/L) and anti-AChR antibodies remained highly positive (92 nm/L). Whereas CT-scan of limb muscles was normal, MRI showed an isolated atrophy with major fatty replacement of the thoracolumbar and paraspinal muscles (Fig. 1). Spine MRI was normal. Because of severe paraspinal muscle atrophy, a deltoid biopsy was performed and this was normal. Thoracic CT revealed no thymomatous mass. The patient condition remained stable during a 3-year follow up. Mycophenolate mofetil was progressively withdrawn one year after the onset of camptocormia without any consequences. 3. Discussion We report the case of a patient with AChR antibody positive MG who presented with isolated myopathic camptocormia unresponsive to cholinesterase inhibitors and immunosuppressive treatments. Camptocormia can be associated with central or peripheral nervous system diseases which have been ruled out in this patient upon clinical evolution, EMG, muscle biopsy and spine MRI. Degenerative or idiopathic camptocormia is unlikely because it is extremely rare before the age of fifty. A steroid induced myopathy could be considered but does not fit with the selective involvement of paraspinal muscles and the lack of evocative histological signs on muscle biopsy such as lipid storage. A more diffuse myopathic process is unlikely in our patient’s case, because of the absence of a family history, the non-involvement of other muscles after 3 years of follow-up and no limb abnormalities were detected on limb muscle CT imaging, EMG or muscle biopsy. Camptocormia secondary to impaired neuromuscular transmission is unlikely in this patient’s case because he did not respond to pyridostigmine, edrophonium or further intravenous immunoglobulin treatment. Furthermore, camptocormia occured while the rest of the patient’s MG symptoms were in remission. Lastly, the withdrawal of mycophenolate did not result in worsening of the patient’s bent spine. Rodolico et al. previously
reported a case of a patient presenting with camptocormia associated with MG with myopathic changes involving cervico-thoracic muscles on EMG and MRI [4]. Similarly, the camptocormia did not respond to prednisolone nor to cholinesterase inhibitor. The authors hypothesized that the axial myopathy could be secondary to an inflammatory myopathy. However, if our patient’s camptocormia had been due to an inflammatory myopathy, then he would have been expected to respond to immunosuppressant treatments. Finally, a myopathic process with marked muscle wasting and fatty replacement is sometimes encountered in MG, specially in muscle-specific kinase (MuSK) antibody positive MG and in severe and chronic AChR antibody positive MG [5]. MG associated myopathic changes usually occur in MG with a very long evolution and previous high dose steroid treatment (>40 mg alternate day) [5]. Therefore, it is possible that the same myopathic process could have selectively involved the paraspinal muscles in our patient. Our case should raise the clinician’s awareness that in some patients MG can be associated with myopathic camptocormia which does not respond to anticholinesterase inhibitors nor to immunosuppressants. In this situation, the clinician should image the paraspinal muscles in search of a myopathic fatty degenerative process, and exclude a more diffuse myopathic process with other investigations such as limb muscle imaging. 4. Conclusion Clinicians should therefore be cautious when using potentially harmful immunosuppressive treatments in MG-associated camptocormia, where patients fail to respond to cholinesterase inhibitors and/or where investigations may demonstrate a more diffuse myopathic process, which is less likely to respond to treatment. References [1] Finsterer J, Strobl W. Presentation, etiology, diagnosis, and management of camptocormia. European Neurology 2010;64:1–8. [2] D’Amelio M, Di Benedetto N, Ragonese P, Daniele O, Brighina F, Fierro B, et al. Dropped head as an unusual presenting sign of myasthenia gravis. Neurological Sciences 2007;28:104–6. [3] Kataoka H, Kiriyama T, Ueno S. Myasthenia gravis can cause camptocormia. Journal of Neurology, Neurosurgery and Psychiatry 2012;83:469–70. [4] Rodolico C, Messina S, Toscano A, Vita G, Gaeta M. Axial myopathy in myasthenia: a misleading cause of dropped head. Muscle and Nerve 2004;29: 329–30. [5] Farrugia ME, Robson MD, Clover L, Anslow P, Newsom-Davis J, Kennett R, et al. MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis. Brain 2006;129:1481–92.