J Neurol (2014) 261:835–836 DOI 10.1007/s00415-014-7307-x
LETTER TO THE EDITORS
When myasthenia gravis is not all V. Damato • P. E. Alboini • A. Mastrorosa A. Dickmann • C. Colosimo • A. Evoli
•
Received: 14 February 2014 / Revised: 26 February 2014 / Accepted: 3 March 2014 / Published online: 15 March 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Dear Sirs, Weakness of the extrinsic ocular muscles (EOM), resulting in fluctuating ptosis and diplopia, is very frequent in myasthenia gravis (MG). Therefore, in patients with an established diagnosis of MG, the onset/worsening of ocular complaints is commonly related to the disease. We hereinafter report two patients whose ocular disturbances were not all justified by MG. Case 1 A 76-year-old woman presented with diplopia and left ptosis. Clinical examination revealed loss of function of left inferior and medial recti muscles, confirmed on Hess screen. Ptosis improved on neostigmine test, and anti-acetylcholine receptor antibodies (AChR Abs) were positive (3.81 nM/l; normal range \0.45). Thyroid function and auto-Abs were normal. The patient was diagnosed with ocular MG and was given prednisone (25 mg/day), with regression of both ptosis and diplopia within three weeks. During steroid tapering she developed vertical strabismus due to non-fluctuating, complete palsy of the left inferior rectus muscle; oral prednisone was gradually increased up to 50 mg/day with no benefit. In this stage neostigmine test was negative; thyroid function and auto-Abs remained within normal limits. After a 3-month V. Damato (&) P. E. Alboini A. Mastrorosa A. Evoli Institute of Neurology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy e-mail: [email protected] A. Dickmann Institute of Ophthalmology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy C. Colosimo Institute of Radiology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy
treatment with 50 mg/day prednisone, the patient underwent brain/orbital magnetic resonance imaging (MRI) with gadolinium, revealing altered signal, swelling, and contrast enhancement of her left inferior rectus muscle, suggesting myositis (Fig. 1a). Methylprednisolone pulse therapy (1,000 mg e.v./day for five consecutive days), followed by oral prednisone on alternate days was administered, with rapid improvement and complete symptom resolution within three months. One year later, a second brain MRI showed a regression of myositis with minimal thinning of the inferior rectus muscle (Fig. 1b). The final diagnosis, in this case, was of ocular MG associated with orbital myositis. Case 2 A 62-year-old woman reported a two-month history of left ptosis, diplopia on the left lateral gaze, and limb fatigability. Brain MRI with gadolinium was negative. Generalized MG was diagnosed on the basis of clinical signs, decremental response on repetitive nerve stimulation, abnormal jitter on single-fiber EMG, and serum AChR Abs detection (2.50 mM/l). Treatment with pyridostigmine resulted in marked improvement of ptosis and limb weakness, whereas diplopia limited to the left lateral gaze remained unaffected. At the following visit six months later, the patient showed pseudo-internuclear ophthalmoplegia. Steroid treatment with prednisone (25 mg/day, for two months) was not effective; thus, dosage was increased up to 50 mg/day, and was maintained steadily for three months with no change in pseudo-internuclear ophthalmoplegia. Thyroid function and auto-Abs were normal on repeated assays. Brain/orbital MRI with gadolinium showed a severe atrophy of the left lateral rectus (Fig. 1c, d). The final diagnosis was generalized MG associated with early EOM atrophy. After three months, a further MRI confirmed these findings, and the patient opted for eye muscle surgery. Prednisone dosage was gradually reduced
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Fig. 1 Neuroradiological findings in our patients: a, b inferior rectus muscle myositis (left orbit). c, d Atrophy of the lateral rectus muscle (left orbit). In the patient with myositis, on the first MRI examination, coronal fat-saturated T2-weighted image (a) shows obvious swelling of the left inferior rectus muscle, with increased signal; other muscles appear completely normal. In the follow-up study, coronal fatsaturated T2-weighted image shows a normal signal of the inferior
rectus muscle with complete resolution of the tumefaction; the muscle appears slightly reduced in thickness. In the second patient, both axial high resolution T2-weighted image (c) and axial contrast-enhanced fat-saturated T1-weighted image (d) demonstrated marked thinning of the lateral rectus muscle in the left orbit; the thinning of the muscle is evident compared to the contra-lateral muscle/orbit.
while pyridostigmine was maintained, as it proved effective in relieving ptosis and limb weakness. MG symptoms typically fluctuate and, in the great majority of patients, improve significantly on steroid treatment [1]. In our patients, ptosis—and in case 2, also limb weakness—was consistent with the diagnosis. On the other hand, diplopia did not appear to be justified by MG, as it was fixed and unresponsive to high-dose prednisone. Considering the possibility of associated diseases was crucial to a correct diagnosis and management of very rare conditions. Orbital myositis can be related to systemic or local inflammatory diseases and may occur in association with several autoimmune conditions [2, 3]. Pseudo-internuclear ophthalmoplegia, when associated with EOM atrophy, is uncommon in MG [4]. To date, it has been reported in four patients total, one of them with AChR Abs and another with muscle-specific kinase (MuSK) Abs [4, 5]. While in the aforementioned cases atrophy occurred in the context of slowly progressive ophthalmoplegia, in our patient it developed in less than one year after onset. Early muscle atrophy can be seen occasionally in patients with antiMuSK antibodies [6], but it is distinctly rare in AChRpositive MG. Our report emphasizes the importance of reconsidering symptom etiology when the clinical course is atypical. In association with MG, one of our patients developed a rare inflammatory condition that required high-dose pulse
methylprednisolone [7]; in the other, ocular palsy was associated with muscle atrophy, possibly related to MG but no longer responsive to steroid treatment.
123
Conflicts of interest of interest.
The authors declare that they have no conflict
Ethical standard Patients gave informed consent to the study, which was approved by the local ethics committee (Protocol no 506/14).
References 1. Kupersmith MJ, Ying G (2005) Ocular motor dysfunction and ptosis in ocular myasthenia gravis: effects of treatment. Br J Ophthalmol 89:1330–1334 2. Cerman E, Esen F, Eraslan M, et al. Orbital myositis associated with celiac disease. Int Ophthalmol Epub 2013 Jul 11 3. Ssi-Yan-Kai I, Pearson A (2012) Orbital myositis and psoriatic arthritis. Can J Ophthalmol 47:42–43 4. Okamoto K, Ito J, Tokiguchi S et al (1996) Atrophy of bilateral extraocular muscles. CT and clinic features of seven patients. J Neuroophthalmol 16:286–288 5. Chan JW, Orrison WW (2007) Ocular myasthenia: a rare presentation with MuSK antibody and bilateral extraocular muscle atrophy. Br J Ophthalmol 91:842–843 6. Zouvelou V, Rentzos M, Toulas P et al (2011) MRI evidence of early muscle atrophy in MuSK positive myasthenia gravis. J Neuroimaging 21(3):303–305 7. Gordon LK (2006) Orbital inflammatory disease: a diagnostic and therapeutic challenge. Eye 20:1196–1206
LETTER TO THE EDITORS
When myasthenia gravis is not all V. Damato • P. E. Alboini • A. Mastrorosa A. Dickmann • C. Colosimo • A. Evoli
•
Received: 14 February 2014 / Revised: 26 February 2014 / Accepted: 3 March 2014 / Published online: 15 March 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Dear Sirs, Weakness of the extrinsic ocular muscles (EOM), resulting in fluctuating ptosis and diplopia, is very frequent in myasthenia gravis (MG). Therefore, in patients with an established diagnosis of MG, the onset/worsening of ocular complaints is commonly related to the disease. We hereinafter report two patients whose ocular disturbances were not all justified by MG. Case 1 A 76-year-old woman presented with diplopia and left ptosis. Clinical examination revealed loss of function of left inferior and medial recti muscles, confirmed on Hess screen. Ptosis improved on neostigmine test, and anti-acetylcholine receptor antibodies (AChR Abs) were positive (3.81 nM/l; normal range \0.45). Thyroid function and auto-Abs were normal. The patient was diagnosed with ocular MG and was given prednisone (25 mg/day), with regression of both ptosis and diplopia within three weeks. During steroid tapering she developed vertical strabismus due to non-fluctuating, complete palsy of the left inferior rectus muscle; oral prednisone was gradually increased up to 50 mg/day with no benefit. In this stage neostigmine test was negative; thyroid function and auto-Abs remained within normal limits. After a 3-month V. Damato (&) P. E. Alboini A. Mastrorosa A. Evoli Institute of Neurology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy e-mail: [email protected] A. Dickmann Institute of Ophthalmology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy C. Colosimo Institute of Radiology, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy
treatment with 50 mg/day prednisone, the patient underwent brain/orbital magnetic resonance imaging (MRI) with gadolinium, revealing altered signal, swelling, and contrast enhancement of her left inferior rectus muscle, suggesting myositis (Fig. 1a). Methylprednisolone pulse therapy (1,000 mg e.v./day for five consecutive days), followed by oral prednisone on alternate days was administered, with rapid improvement and complete symptom resolution within three months. One year later, a second brain MRI showed a regression of myositis with minimal thinning of the inferior rectus muscle (Fig. 1b). The final diagnosis, in this case, was of ocular MG associated with orbital myositis. Case 2 A 62-year-old woman reported a two-month history of left ptosis, diplopia on the left lateral gaze, and limb fatigability. Brain MRI with gadolinium was negative. Generalized MG was diagnosed on the basis of clinical signs, decremental response on repetitive nerve stimulation, abnormal jitter on single-fiber EMG, and serum AChR Abs detection (2.50 mM/l). Treatment with pyridostigmine resulted in marked improvement of ptosis and limb weakness, whereas diplopia limited to the left lateral gaze remained unaffected. At the following visit six months later, the patient showed pseudo-internuclear ophthalmoplegia. Steroid treatment with prednisone (25 mg/day, for two months) was not effective; thus, dosage was increased up to 50 mg/day, and was maintained steadily for three months with no change in pseudo-internuclear ophthalmoplegia. Thyroid function and auto-Abs were normal on repeated assays. Brain/orbital MRI with gadolinium showed a severe atrophy of the left lateral rectus (Fig. 1c, d). The final diagnosis was generalized MG associated with early EOM atrophy. After three months, a further MRI confirmed these findings, and the patient opted for eye muscle surgery. Prednisone dosage was gradually reduced
123
836
J Neurol (2014) 261:835–836
Fig. 1 Neuroradiological findings in our patients: a, b inferior rectus muscle myositis (left orbit). c, d Atrophy of the lateral rectus muscle (left orbit). In the patient with myositis, on the first MRI examination, coronal fat-saturated T2-weighted image (a) shows obvious swelling of the left inferior rectus muscle, with increased signal; other muscles appear completely normal. In the follow-up study, coronal fatsaturated T2-weighted image shows a normal signal of the inferior
rectus muscle with complete resolution of the tumefaction; the muscle appears slightly reduced in thickness. In the second patient, both axial high resolution T2-weighted image (c) and axial contrast-enhanced fat-saturated T1-weighted image (d) demonstrated marked thinning of the lateral rectus muscle in the left orbit; the thinning of the muscle is evident compared to the contra-lateral muscle/orbit.
while pyridostigmine was maintained, as it proved effective in relieving ptosis and limb weakness. MG symptoms typically fluctuate and, in the great majority of patients, improve significantly on steroid treatment [1]. In our patients, ptosis—and in case 2, also limb weakness—was consistent with the diagnosis. On the other hand, diplopia did not appear to be justified by MG, as it was fixed and unresponsive to high-dose prednisone. Considering the possibility of associated diseases was crucial to a correct diagnosis and management of very rare conditions. Orbital myositis can be related to systemic or local inflammatory diseases and may occur in association with several autoimmune conditions [2, 3]. Pseudo-internuclear ophthalmoplegia, when associated with EOM atrophy, is uncommon in MG [4]. To date, it has been reported in four patients total, one of them with AChR Abs and another with muscle-specific kinase (MuSK) Abs [4, 5]. While in the aforementioned cases atrophy occurred in the context of slowly progressive ophthalmoplegia, in our patient it developed in less than one year after onset. Early muscle atrophy can be seen occasionally in patients with antiMuSK antibodies [6], but it is distinctly rare in AChRpositive MG. Our report emphasizes the importance of reconsidering symptom etiology when the clinical course is atypical. In association with MG, one of our patients developed a rare inflammatory condition that required high-dose pulse
methylprednisolone [7]; in the other, ocular palsy was associated with muscle atrophy, possibly related to MG but no longer responsive to steroid treatment.
123
Conflicts of interest of interest.
The authors declare that they have no conflict
Ethical standard Patients gave informed consent to the study, which was approved by the local ethics committee (Protocol no 506/14).
References 1. Kupersmith MJ, Ying G (2005) Ocular motor dysfunction and ptosis in ocular myasthenia gravis: effects of treatment. Br J Ophthalmol 89:1330–1334 2. Cerman E, Esen F, Eraslan M, et al. Orbital myositis associated with celiac disease. Int Ophthalmol Epub 2013 Jul 11 3. Ssi-Yan-Kai I, Pearson A (2012) Orbital myositis and psoriatic arthritis. Can J Ophthalmol 47:42–43 4. Okamoto K, Ito J, Tokiguchi S et al (1996) Atrophy of bilateral extraocular muscles. CT and clinic features of seven patients. J Neuroophthalmol 16:286–288 5. Chan JW, Orrison WW (2007) Ocular myasthenia: a rare presentation with MuSK antibody and bilateral extraocular muscle atrophy. Br J Ophthalmol 91:842–843 6. Zouvelou V, Rentzos M, Toulas P et al (2011) MRI evidence of early muscle atrophy in MuSK positive myasthenia gravis. J Neuroimaging 21(3):303–305 7. Gordon LK (2006) Orbital inflammatory disease: a diagnostic and therapeutic challenge. Eye 20:1196–1206
