Clin Neuroradiol DOI 10.1007/s00062-014-0364-9
Correspondence
Ultrasonography of Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM) C. Neubauer · H. Gruber · J. Bäuerle · K. Egger
Received: 20 August 2014 / Accepted: 20 November 2014 © Springer-Verlag Berlin Heidelberg 2014
Introduction
Case Report
The multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) or Lewis–Sumner syndrome is a rare acquired neuropathy. It is distinguished from other acquired demyelinating polyneuropathies such as the chronic inflammatory demyelinating polyneuropathy (CIDP) by asymmetric motor and sensory impairment, and the multifocal motor neuropathy (MMN) by the presence of sensory symptoms [1]. We report a case of a neuropathy with an enlargement of the right distal sciatic and proximal tibial nerve in ultrasonography, with corresponding motor and sensory symptoms and conduction block of the tibial nerve representing MADSAM as confirmed by electrophysiological investigations, magnetic resonance imaging (MRI) and biopsy.
A 61-year-old man presented with asymmetric weakness of the right lower leg, especially of the plantarflexion and with intermittent oedemas of the right lower limb. These symptoms first appeared more than 10 years ago and showed a slow progression, with exacerbations 3 years and again 1 year ago. They are accompanied by sensory impairment with plantar, sometimes ascending paraesthesia. Previous magnetic resonance imaging (MRI) examinations of the lumbar spine, the lumbosacral plexus, the right knee, the right lower leg, the right ankle and the right forefoot showed no specific findings. In neurophysiological investigations, the right tibial nerve had a prolonged distal latency, reduced conduction velocity, delayed F waves and reduced amplitude, with a conduction block at the level of the popliteal fossa. The right peroneal and sural nerves were unaffected. Sensory evoked potentials indicated a severe afferent disorder of the right leg, with a weak efferent disorder. The cerebrospinal fluid protein content was mildly elevated. An ultrasound examination revealed a long-distance thickening of the right sciatic nerve continuing to the proximal tibial nerve, with diffuse hypoechogenic hypertrophy of the fascicles. Also, there was an increased circumference of the tibial nerve of approximately 4.05 cm, and an enlarged cross-sectional area of 1.12 cm2 was defined (Fig. 1a). Duplex sonography showed neither marked hypervascularisation nor further focal pathologies. To rule out enhancement of the nerve, an additional MRI of the right upper leg was performed, which revealed a T2w-hyperintense and T1w-isointense thickened sciatic and proximal tibial nerve without enhancement throughout the whole lesion after intravenous gadolinium-based contrast agent application (Gadobenate Dimeglumine, MultiHance/
K. Egger () Department of Neuroradiology, University Medical Center Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany e-mail: [email protected] C. Neubauer Department of Radiology, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany H. Gruber Department of Radiology, Innsbruck Medical University, Anichstraße 35, 6020 Innsbruck, Austria J. Bäuerle Department of Neurology, University Medical Center Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany
13
2
C. Neubauer et al.
Fig. 1 Ultrasonography shows enlargement of the right tibial nerve in the proximal part of the popliteal fossa with an increased cross-sectional area on transverse scan of 1.12 cm2 (a, solid line) in comparison with 0.27 cm2 of the contralateral tibial nerve (b, dotted line)
Fig. 2 Magnetic resonance imaging showing an enlarged right distal sciatic/tibial nerve (arrows) with isointense signal on T1-weighted images (a, in comparison with the left side), hyperintense signal on fat-suppressed T2-weighted images (b), and without enhancement after gadolinium administration (c)
Bracco Imaging; 0.1 mmol/kg of body weight; Fig. 2). Soleus, posterior tibial, flexor digitorum longus and flexor hallucis longus muscles showed a T2w-hyperintense signal, which might refer to an oedema or possibly increased blood volume [2, 3]. A Baker cyst of the right knee had no contact to or constricting impact on the nerve. Due to the hypothetic diagnosis of a perineurioma, a biopsy of the right sciatic nerve was performed to rule
13
out a tumour: endoneurial oedema, Schwann cells in an onion bulb formation, smaller regenerating axons and a reduced number of normal axons were detected together with some inflammatory cells but without signs of vasculitis or tomaculous swelling of the myelin sheath. There was no evidence for any neoplastic lesion like perineurioma or neurofibroma. After the uncomplicated biopsy, the patient showed no new symptoms or neurological deficits.
Ultrasonography of Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM)
These results are concordant with the asymmetric chronic acquired demyelinating polyneuropathy MADSAM. Discussion High-resolution sonography supplies a reliable and costefficient method for large area-covering investigations of peripheral nerves. Enlargement of peripheral nerves in sonography can account for several causes, including trauma, lipomatosis, neoplasms such as perineuriomas, benign or malignant peripheral nerve sheath tumours or fibrolipomas, hereditary neuropathies such as hereditary motor sensory neuropathy, hereditary neuropathy with liability to pressure palsies (HNPP) or chronic acquired demyelinating polyneuropathies such as CIDP, MMN or MADSAM [4]. Benign and malignant neoplasms might present as inhomogeneous masses with cystic lesions or calcifications, septations, the split-fat sign (rim of fat) or a target sign. Especially in malignant lesions infiltrative growth, indistinct margins or hypervascularisation in duplex sonography might be seen, but they might also have a well-circumscribed hypoechogenic appearance [5]. MADSAM or Lewis–Sumner syndrome was first described by Lewis in 1982 [6] and is discussed to be an asymmetrical variant of CIDP. The exact prevalence of MADSAM is still unknown, but it is estimated to be approximately 0.08–0.6 per 100.000 individuals [7]. The clinical course usually presents with a slowly progressive weakness accompanied by sensory symptoms including numbness and paraesthesia in single peripheral nerve areas with an asymmetric multifocal distribution and a reduction or loss of muscle reflexes. In one study, the symptoms were initially unilateral in 74 % and unifocal in 21 % of patients. In the majority of these cases, the upper extremities, and in one-third of these cases, the lower extremities, were initially affected [8]. The symptoms are reported to remain unifocal in some cases for several years before spreading to other regions [7, 9]. Electrophysiological findings involve signs of demyelination such as prolonged distal latency, slowed conduction velocity, delayed or absent F waves, a conduction block and, in contrast to MMN, abnormalities in sensory nerve conduction. Cerebral fluid investigation shows a mild increase of protein in approximately 60–80 % of patients [1]. In CIDP and MADSAM, sonography is reported to detect enlargement of peripheral nerves, with a hypoechogenity and a loss of the normal fascicular pattern due to enlarged single hypoechogenic nerve fascicles at sites of conduction blocks [10, 11]. In MRI, a hyperintense signal on fat-suppressed T2-weighted images and an isointense signal on T1-weighted images of the nerve can be seen [12]. After gadolinium admi-
3
nistration, enhancement of the nerve is described [7], whereas in another report, no enhancement could be detected [9]. Histopathological findings include a subperineurial oedema, a decrease in myelinated fibres, the presence of remyelinating fibres and Schwann cells in onion bulb formations. Signs of inflammation without evidence of vasculitis might be present as well [6]. Altogether, an unstable clinical course of a neuropathy (with an unclear onset) without detection of a circumscribed focal pathology by sonography should make us think of at least a form of polyneuropathy, especially if the clinical distribution pattern is conspicuous: this may be fortified by a diffuse alteration of whole nerves with fascicular swelling. The definite diagnosis follows then by synopsis of the findings of all diagnostic fields, in some cases, even by biopsy. Conflict of Interest The authors have no conflict of interest related to this article.
References 1. Saperstein DS, Katz JS, Amato AA, Barohn RJ. Clinical spectrum of chronic acquired demyelinating polyneuropathies. Muscle Nerve. 2001;24:311–24. 2. Hayashi Y, Ikata T, Takai H, Takata S, Ishikawa M, Sogabe T, Koga K. Effect of peripheral nerve injury on nuclear magnetic resonance relaxation times of rat skeletal muscle. Invest Radiol. 1997;32:135–9. 3. Wessig C, Koltzenburg M, Reiners K, Solymosi L, Bendszus M. Muscle magnetic resonance imaging of denervation and reinnervation: correlation with electrophysiology and histology. Exp Neurol. 2004;185:254–61. 4. De Smet K, De Maeseneer M, Talebian Yazdi A, Stadnik T, De Mey J. MRI in hypertrophic mono- and polyneuropathies. Clin Radiol. 2013;68:317–22. 5. Abreu E, Aubert S, Wavreille G, Gheno R, Canella C, Cotten A. Peripheral tumor and tumor-like neurogenic lesions. Eur J Radiol. 2013;82:38–50. 6. Lewis RA, Sumner AJ, Brown MJ, Asbury AK. Multifocal demyelinating neuropathy with persistent conduction block. Neurology. 1982;32:958–64. 7. Allen DC, Smallman AC, Mills KR. Multifocal acquired demyelinating sensory and motor neuropathy presenting as a peripheral nerve tumor. Muscle Nerve. 2006;34:373–9. 8. Viala K, Renie L, Maisonobe T, Behin A, Neil J, Leger JM, Bouche P. Follow-up study and response to treatment in 23 patients with Lewis–Sumner syndrome. Brain. 2004;127:2010–7. 9. Van den Berg-Vos RM, Van den Berg LH, Franssen H, Vermeulen M, Witkamp TD, Jansen GH, van Es HW, Kerkhoff H, Wokke JH. Multifocal inflammatory demyelinating neuropathy: a distinct clinical entity? Neurology. 2000;54:26–32. 10. Granata G, Pazzaglia C, Calandro P, Luigetti M, Martinoli C, Sabatelli M, Padua L. Ultrasound visualization of nerve morphological alteration at the site of conduction block. Muscle Nerve. 2009;40:1068–70. 11. Scheidl E, Böhm J, Simó M, Rózsa C, Bereznai B, Kovács T, Arányi Z. Ultrasonography of MADSAM neuropathy: focal nerve enlargements at sites of existing and resolved conduction blocks. Neuromuscul Disord. 2012;22:627–31. 12. Rajabally YA, Knopp MJ, Martin-Lamp D, Morlese J. Diagnostic value of MR imaging in the Lewis-Sumner syndrome: a case series. J Neurol Sci. 2014;34:182–5.
13
Correspondence
Ultrasonography of Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM) C. Neubauer · H. Gruber · J. Bäuerle · K. Egger
Received: 20 August 2014 / Accepted: 20 November 2014 © Springer-Verlag Berlin Heidelberg 2014
Introduction
Case Report
The multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) or Lewis–Sumner syndrome is a rare acquired neuropathy. It is distinguished from other acquired demyelinating polyneuropathies such as the chronic inflammatory demyelinating polyneuropathy (CIDP) by asymmetric motor and sensory impairment, and the multifocal motor neuropathy (MMN) by the presence of sensory symptoms [1]. We report a case of a neuropathy with an enlargement of the right distal sciatic and proximal tibial nerve in ultrasonography, with corresponding motor and sensory symptoms and conduction block of the tibial nerve representing MADSAM as confirmed by electrophysiological investigations, magnetic resonance imaging (MRI) and biopsy.
A 61-year-old man presented with asymmetric weakness of the right lower leg, especially of the plantarflexion and with intermittent oedemas of the right lower limb. These symptoms first appeared more than 10 years ago and showed a slow progression, with exacerbations 3 years and again 1 year ago. They are accompanied by sensory impairment with plantar, sometimes ascending paraesthesia. Previous magnetic resonance imaging (MRI) examinations of the lumbar spine, the lumbosacral plexus, the right knee, the right lower leg, the right ankle and the right forefoot showed no specific findings. In neurophysiological investigations, the right tibial nerve had a prolonged distal latency, reduced conduction velocity, delayed F waves and reduced amplitude, with a conduction block at the level of the popliteal fossa. The right peroneal and sural nerves were unaffected. Sensory evoked potentials indicated a severe afferent disorder of the right leg, with a weak efferent disorder. The cerebrospinal fluid protein content was mildly elevated. An ultrasound examination revealed a long-distance thickening of the right sciatic nerve continuing to the proximal tibial nerve, with diffuse hypoechogenic hypertrophy of the fascicles. Also, there was an increased circumference of the tibial nerve of approximately 4.05 cm, and an enlarged cross-sectional area of 1.12 cm2 was defined (Fig. 1a). Duplex sonography showed neither marked hypervascularisation nor further focal pathologies. To rule out enhancement of the nerve, an additional MRI of the right upper leg was performed, which revealed a T2w-hyperintense and T1w-isointense thickened sciatic and proximal tibial nerve without enhancement throughout the whole lesion after intravenous gadolinium-based contrast agent application (Gadobenate Dimeglumine, MultiHance/
K. Egger () Department of Neuroradiology, University Medical Center Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany e-mail: [email protected] C. Neubauer Department of Radiology, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany H. Gruber Department of Radiology, Innsbruck Medical University, Anichstraße 35, 6020 Innsbruck, Austria J. Bäuerle Department of Neurology, University Medical Center Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany
13
2
C. Neubauer et al.
Fig. 1 Ultrasonography shows enlargement of the right tibial nerve in the proximal part of the popliteal fossa with an increased cross-sectional area on transverse scan of 1.12 cm2 (a, solid line) in comparison with 0.27 cm2 of the contralateral tibial nerve (b, dotted line)
Fig. 2 Magnetic resonance imaging showing an enlarged right distal sciatic/tibial nerve (arrows) with isointense signal on T1-weighted images (a, in comparison with the left side), hyperintense signal on fat-suppressed T2-weighted images (b), and without enhancement after gadolinium administration (c)
Bracco Imaging; 0.1 mmol/kg of body weight; Fig. 2). Soleus, posterior tibial, flexor digitorum longus and flexor hallucis longus muscles showed a T2w-hyperintense signal, which might refer to an oedema or possibly increased blood volume [2, 3]. A Baker cyst of the right knee had no contact to or constricting impact on the nerve. Due to the hypothetic diagnosis of a perineurioma, a biopsy of the right sciatic nerve was performed to rule
13
out a tumour: endoneurial oedema, Schwann cells in an onion bulb formation, smaller regenerating axons and a reduced number of normal axons were detected together with some inflammatory cells but without signs of vasculitis or tomaculous swelling of the myelin sheath. There was no evidence for any neoplastic lesion like perineurioma or neurofibroma. After the uncomplicated biopsy, the patient showed no new symptoms or neurological deficits.
Ultrasonography of Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM)
These results are concordant with the asymmetric chronic acquired demyelinating polyneuropathy MADSAM. Discussion High-resolution sonography supplies a reliable and costefficient method for large area-covering investigations of peripheral nerves. Enlargement of peripheral nerves in sonography can account for several causes, including trauma, lipomatosis, neoplasms such as perineuriomas, benign or malignant peripheral nerve sheath tumours or fibrolipomas, hereditary neuropathies such as hereditary motor sensory neuropathy, hereditary neuropathy with liability to pressure palsies (HNPP) or chronic acquired demyelinating polyneuropathies such as CIDP, MMN or MADSAM [4]. Benign and malignant neoplasms might present as inhomogeneous masses with cystic lesions or calcifications, septations, the split-fat sign (rim of fat) or a target sign. Especially in malignant lesions infiltrative growth, indistinct margins or hypervascularisation in duplex sonography might be seen, but they might also have a well-circumscribed hypoechogenic appearance [5]. MADSAM or Lewis–Sumner syndrome was first described by Lewis in 1982 [6] and is discussed to be an asymmetrical variant of CIDP. The exact prevalence of MADSAM is still unknown, but it is estimated to be approximately 0.08–0.6 per 100.000 individuals [7]. The clinical course usually presents with a slowly progressive weakness accompanied by sensory symptoms including numbness and paraesthesia in single peripheral nerve areas with an asymmetric multifocal distribution and a reduction or loss of muscle reflexes. In one study, the symptoms were initially unilateral in 74 % and unifocal in 21 % of patients. In the majority of these cases, the upper extremities, and in one-third of these cases, the lower extremities, were initially affected [8]. The symptoms are reported to remain unifocal in some cases for several years before spreading to other regions [7, 9]. Electrophysiological findings involve signs of demyelination such as prolonged distal latency, slowed conduction velocity, delayed or absent F waves, a conduction block and, in contrast to MMN, abnormalities in sensory nerve conduction. Cerebral fluid investigation shows a mild increase of protein in approximately 60–80 % of patients [1]. In CIDP and MADSAM, sonography is reported to detect enlargement of peripheral nerves, with a hypoechogenity and a loss of the normal fascicular pattern due to enlarged single hypoechogenic nerve fascicles at sites of conduction blocks [10, 11]. In MRI, a hyperintense signal on fat-suppressed T2-weighted images and an isointense signal on T1-weighted images of the nerve can be seen [12]. After gadolinium admi-
3
nistration, enhancement of the nerve is described [7], whereas in another report, no enhancement could be detected [9]. Histopathological findings include a subperineurial oedema, a decrease in myelinated fibres, the presence of remyelinating fibres and Schwann cells in onion bulb formations. Signs of inflammation without evidence of vasculitis might be present as well [6]. Altogether, an unstable clinical course of a neuropathy (with an unclear onset) without detection of a circumscribed focal pathology by sonography should make us think of at least a form of polyneuropathy, especially if the clinical distribution pattern is conspicuous: this may be fortified by a diffuse alteration of whole nerves with fascicular swelling. The definite diagnosis follows then by synopsis of the findings of all diagnostic fields, in some cases, even by biopsy. Conflict of Interest The authors have no conflict of interest related to this article.
References 1. Saperstein DS, Katz JS, Amato AA, Barohn RJ. Clinical spectrum of chronic acquired demyelinating polyneuropathies. Muscle Nerve. 2001;24:311–24. 2. Hayashi Y, Ikata T, Takai H, Takata S, Ishikawa M, Sogabe T, Koga K. Effect of peripheral nerve injury on nuclear magnetic resonance relaxation times of rat skeletal muscle. Invest Radiol. 1997;32:135–9. 3. Wessig C, Koltzenburg M, Reiners K, Solymosi L, Bendszus M. Muscle magnetic resonance imaging of denervation and reinnervation: correlation with electrophysiology and histology. Exp Neurol. 2004;185:254–61. 4. De Smet K, De Maeseneer M, Talebian Yazdi A, Stadnik T, De Mey J. MRI in hypertrophic mono- and polyneuropathies. Clin Radiol. 2013;68:317–22. 5. Abreu E, Aubert S, Wavreille G, Gheno R, Canella C, Cotten A. Peripheral tumor and tumor-like neurogenic lesions. Eur J Radiol. 2013;82:38–50. 6. Lewis RA, Sumner AJ, Brown MJ, Asbury AK. Multifocal demyelinating neuropathy with persistent conduction block. Neurology. 1982;32:958–64. 7. Allen DC, Smallman AC, Mills KR. Multifocal acquired demyelinating sensory and motor neuropathy presenting as a peripheral nerve tumor. Muscle Nerve. 2006;34:373–9. 8. Viala K, Renie L, Maisonobe T, Behin A, Neil J, Leger JM, Bouche P. Follow-up study and response to treatment in 23 patients with Lewis–Sumner syndrome. Brain. 2004;127:2010–7. 9. Van den Berg-Vos RM, Van den Berg LH, Franssen H, Vermeulen M, Witkamp TD, Jansen GH, van Es HW, Kerkhoff H, Wokke JH. Multifocal inflammatory demyelinating neuropathy: a distinct clinical entity? Neurology. 2000;54:26–32. 10. Granata G, Pazzaglia C, Calandro P, Luigetti M, Martinoli C, Sabatelli M, Padua L. Ultrasound visualization of nerve morphological alteration at the site of conduction block. Muscle Nerve. 2009;40:1068–70. 11. Scheidl E, Böhm J, Simó M, Rózsa C, Bereznai B, Kovács T, Arányi Z. Ultrasonography of MADSAM neuropathy: focal nerve enlargements at sites of existing and resolved conduction blocks. Neuromuscul Disord. 2012;22:627–31. 12. Rajabally YA, Knopp MJ, Martin-Lamp D, Morlese J. Diagnostic value of MR imaging in the Lewis-Sumner syndrome: a case series. J Neurol Sci. 2014;34:182–5.
13
