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Isolated inflammatory myopathy with rimmed vacuoles presenting with dropped head
Neuromuscular Disorders 19 (2009) 853–855
Contents lists available at ScienceDirect
Neuromuscular Disorders journal homepage: www.elsevier.com/locate/nmd
Case report
Isolated inflammatory myopathy with rimmed vacuoles presenting with dropped head Hiroshi Kataoka a,*, Kazuma Sugie a, Mari Terashima a, Munehisa Koizumi b, Hirosei Horikawa a, Ichizo Nishino c, Ikuya Nonaka c, Satoshi Ueno a a b c
Department of Neurology, Nara Medical University, Kashihara, Nara, Japan Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
a r t i c l e
i n f o
Article history: Received 12 May 2009 Received in revised form 13 August 2009 Accepted 19 August 2009
Keywords: Dropped head Inclusion body Rimmed vacuoles Paraspinal muscles
a b s t r a c t We describe an unusual case of inflammatory myopathy with rimmed vacuoles associated with dropped head syndrome. Muscle biopsy in our patient revealed variations in fiber size with fiber necrosis and regeneration, accompanied by many rimmed vacuoles and areas of endomysial cell infiltration. Electron microscopy demonstrated autophagic vacuoles and tubulofilamentous inclusions. This myopathy can cause dropped head syndrome in a subgroup of patients. Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction Restricted weakness of the extensors of the neck is a relatively rare condition, designated as the ‘‘dropped head syndrome” (DHS). Dropped head syndrome may be present in a variety of neurological diseases, including neuromuscular or neurodegenerative disorders, as well as in non-inflammatory, inflammatory, dystrophic, or metabolic myopathies. Muscle biopsies have usually shown nonspecific myopathic features, including fiber splitting, variations in fiber size, moth-eaten fibers, type 2 atrophy, and internal nuclei [1]. Rarely, inflammatory processes have been noted in patients with inclusion body myositis (IBM) [2] or focal myositis [3–5]. We described an unusual case of inflammatory myopathy with rimmed vacuoles that was associated with DHS.
2. Case report A 77-year-old woman with a history of surgery for a femoral fracture experienced difficulty in maintaining an erect posture of her neck and lifting her chin off her chest. These symptoms developed gradually over the course of 13 months. Generalized muscle
* Corresponding author. Address: Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Tel.: +81 744 29 8860; fax: +81 744 24 6065. E-mail address: [email protected] (H. Kataoka). 0960-8966/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2009.08.006
weakness, ptosis, diplopia, and fasciculation were absent. There were no family history of neuromuscular disease and no exposure to neuroleptic medications. She had a forward drop of the head, with a Manual Muscle Test (MMT) score of 2-strength (Fig. 1). Muscle strength in all other muscle groups, including the neck flexors and finger flexors, was preserved, and there was no atrophy of any muscle, including the quadriceps. Deep tendon reflexes were normal, with no pathological reflexes. The results of other neurological examinations were negative. Serum creatine kinase (269 U/l), aldolase (5.0 IU/l), aspartate aminotransferase (37 IU/l), and lactate dehydrogenase (327 IU/l) were increased. The erythrocyte sedimentation rate, leukocyte count, and C-reactive protein level were normal. Blood cell counts and the results of routine biochemical analysis were normal. Hepatitis C virus antibody was positive, but human immunodeficiency virus and human T-cell leukemia virus were negative. Various immune disorder antibodies, including anti-Jo1 and acetylcholine receptor antibodies, were negative, and serum thyroid-stimulating hormone, adrenocorticotropic hormone, parathyroid hormone and cortisol were normal. Pyruvic and lactic acids were not elevated. Electromyography of the paraspinal muscles at the levels of C5 and Th7 demonstrated reduced amplitudes (below 0.3 mV) and durations (below 5 ms) of motor unit action potentials and fibrillation potentials. All other muscles examined (biceps, triceps, adductor of thumb, sternocleidomastoideus, quadriceps, gastrocnemius, and tibialis anterior) showed no evidence of neuropathic or myopathic motor unit action potentials. A surface electromyogram showed no
854
H. Kataoka et al. / Neuromuscular Disorders 19 (2009) 853–855
Fig. 1. (Left) Before treatment with oral prednisone, the patient presented with dropped head on natural standing. (Right) After treatment with oral prednisone, the dropped head was markedly diminished on natural standing.
spontaneous activity in the left or right sternocleidomastoideus, trapezius, or paraspinal muscles at the level of C5. The results of nerve conduction studies of the four limbs were normal. Magnetic resonance imaging (MRI) of the erector muscles from the level of C1 to L5 showed abnormal high signals in the splenius from C3 to C6 on fat-suppressed and T2-weighted images (Fig. 2), but no evidence of muscular atrophy or abnormal signals in other erector muscles. Skeletal muscle MRI of both forearms and thighs revealed no evidence of atrophy or abnormal signals. Cervical MRI showed mild spondylotic changes and a narrow canal, without compression of the spinal cord, from C3 to C6, associated with dislocation of the C4 and C5 vertebrae. Biopsy of the involved splenius showed moderate variations in fiber size and necrotic and regenerating fibers, accompanied by many rimmed vacuoles and endomysial cell infiltration (Fig. 3A and B). The cell infiltrations consisted primarily of T-cells (CD8+), which was compatible with sporadic IBM. Inflammatory cells did not invade non-necrotic fibers. Immunohistochemistry for MHC-I showed sarcolemmal and internal labeling of MHC-I in some scattered muscle fibers of the endomysium. NADH-TR staining did not show fiber type predominance, but the intermyofibrillar network was clearly disorganized. No abnormal findings were detected on immunohistochemical staining for dystrophin, dysferlin, caveolin 3, or alpha, beta, gamma, and delta sarcoglycans. Electron microscopy demonstrated autophagic
vacuoles and tubulofilamentous inclusions measuring about 20 nm in width (Fig. 3C). The patient received oral prednisone 30 mg/d for 2 weeks, and neck extensor weakness improved to an MMT score of 5-strength. The dropped head had disappeared when the patient assumed a natural position (Fig. 1). Repeated skeletal muscle MRI showed that the abnormal signals of the splenius had resolved (Fig. 2). After that, she received only oral prednisone (10–20 mg/day), but the dropped head had reappeared after 12 months of follow-up. At 28 months after the onset of dropped head, the dropped head persisted, but weakness in her four limbs was not evident. Cervical skeletal muscle MRI showed mild atrophy of the erector muscles from the level of C3 to C6, but no evidence of abnormal signals. Atrophy or abnormal signals were not evident in the forearms or lower limbs by skeletal muscle MRI.
3. Discussion Muscle biopsy in our patient revealed variations in fiber size with fiber necrosis and regeneration, accompanied by many rimmed vacuoles and areas of endomysial cell infiltration. Our patient had weakness restricted to the neck extensor muscles, and further progression did not occur. In one patient with IBM who presented with weakness of the erector muscles, weakness
Fig. 2. T2-weighted MR image of the erector muscles at the C4 level showed abnormal high signal intensity before steroid treatment (left, white arrows), but the high signals had resolved after treatment (right).
H. Kataoka et al. / Neuromuscular Disorders 19 (2009) 853–855
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Fig. 3. Histological findings of a biopsy specimen of the splenius capitis muscle from the patient. Hematoxylin and eosin staining shows increased variation in fiber size, myofiber necrosis and regeneration (white asterisk), and cellular infiltration and proliferation of endomysial connective tissue (A: scale = 40 lm). Modified Gomori-trichrome staining shows some rimmed vacuoles in muscle fibers (B: scale = 20 lm). On ultrastructural analysis, scattered in the muscle fibers are autophagic vacuoles containing cytoplasmic debris, electron dense material, and myeloid bodies (C). Tubulofilamentous nuclear inclusions are noted (D). The region in square is magnified. The diameter of the inclusions is about 20 nm. Original magnification: C, 8000; D, 25,000.
in the extremities developed subsequently [2]. In a large series of patients with IBM [6], involvement of the paraspinal muscles was absent, and involvement of the neck muscles was very rare. While, myositis can also show MRI, EMG, and clinical findings in restricted neck extensor muscles similar to those in our patient and might have caused the dropped head. Polymyositis and dermatomyositis usually involve the thigh and pelvic musculature bilaterally and symmetrically; neck involvement can occur late in the disease course. However, muscle biopsy in our patient showed no inflammatory cell infiltrates. The present diagnosis is inflammatory myopathy with rimmed vacuoles, but the patient’s general condition may be affected in the future. The reason why certain inflammatory myopathies are restricted to the neck extensor muscles remains uncertain. Frequent mechanical-stretch injury to neck extensor muscles over time associated with loss of tissue elasticity can lead to DHS [7]. In inflammatory myopathies, high blood flow rates may increase contact between T-cells and target antigens, which can lead to T-cell mediated inflammatory conditions, which
may specifically affect extensor muscles in the neck [3]. This myopathy can cause DHS in a subgroup of patients. References [1] Umapathi T, Chaudhry V, Cornblath D, Drachman D, Griffin J, Kuncl R. Head drop and camptocormia. J Neurol Neurosurg Psychiatry 2002;73:1–7. [2] Hund E, Heckl R, Goebel HH, Meinck HM. Inclusion body myositis presenting with isolated erector spinae paresis. Neurology 1995;45:993–4. [3] Kastrup A, Gdynia HJ, Nägele T, Riecker A. Dropped-head syndrome due to steroid responsive focal myositis: a case report and review of the literature. J Neurol Sci 2008;267:162–5. [4] Dominick J, Sheean G, Schleimer J, Wixom C. Response of the dropped head/bent spine syndrome to treatment with intravenous immunoglobulin. Muscle Nerve 2006;33:824–6. [5] Biran I, Cohen O, Diment J, Peyser A, Bahnof R, Steiner I. Focal, steroid responsive myositis causing dropped head syndrome. Muscle Nerve 1999;22:769–71. [6] Lotz BP, Engel AG, Nishino H, Stevens JC, Litchy WJ. Inclusion body myositis. Observations in 40 patients. Brain 1989;112:727–47. [7] Katz JS, Wolfe GI, Burns DK, Bryan WW, Fleckenstein JL, Barohn RJ. Isolated neck extensor myopathy: a common cause of dropped head syndrome. Neurology 1996;46:917–21.
Contents lists available at ScienceDirect
Neuromuscular Disorders journal homepage: www.elsevier.com/locate/nmd
Case report
Isolated inflammatory myopathy with rimmed vacuoles presenting with dropped head Hiroshi Kataoka a,*, Kazuma Sugie a, Mari Terashima a, Munehisa Koizumi b, Hirosei Horikawa a, Ichizo Nishino c, Ikuya Nonaka c, Satoshi Ueno a a b c
Department of Neurology, Nara Medical University, Kashihara, Nara, Japan Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
a r t i c l e
i n f o
Article history: Received 12 May 2009 Received in revised form 13 August 2009 Accepted 19 August 2009
Keywords: Dropped head Inclusion body Rimmed vacuoles Paraspinal muscles
a b s t r a c t We describe an unusual case of inflammatory myopathy with rimmed vacuoles associated with dropped head syndrome. Muscle biopsy in our patient revealed variations in fiber size with fiber necrosis and regeneration, accompanied by many rimmed vacuoles and areas of endomysial cell infiltration. Electron microscopy demonstrated autophagic vacuoles and tubulofilamentous inclusions. This myopathy can cause dropped head syndrome in a subgroup of patients. Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction Restricted weakness of the extensors of the neck is a relatively rare condition, designated as the ‘‘dropped head syndrome” (DHS). Dropped head syndrome may be present in a variety of neurological diseases, including neuromuscular or neurodegenerative disorders, as well as in non-inflammatory, inflammatory, dystrophic, or metabolic myopathies. Muscle biopsies have usually shown nonspecific myopathic features, including fiber splitting, variations in fiber size, moth-eaten fibers, type 2 atrophy, and internal nuclei [1]. Rarely, inflammatory processes have been noted in patients with inclusion body myositis (IBM) [2] or focal myositis [3–5]. We described an unusual case of inflammatory myopathy with rimmed vacuoles that was associated with DHS.
2. Case report A 77-year-old woman with a history of surgery for a femoral fracture experienced difficulty in maintaining an erect posture of her neck and lifting her chin off her chest. These symptoms developed gradually over the course of 13 months. Generalized muscle
* Corresponding author. Address: Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Tel.: +81 744 29 8860; fax: +81 744 24 6065. E-mail address: [email protected] (H. Kataoka). 0960-8966/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2009.08.006
weakness, ptosis, diplopia, and fasciculation were absent. There were no family history of neuromuscular disease and no exposure to neuroleptic medications. She had a forward drop of the head, with a Manual Muscle Test (MMT) score of 2-strength (Fig. 1). Muscle strength in all other muscle groups, including the neck flexors and finger flexors, was preserved, and there was no atrophy of any muscle, including the quadriceps. Deep tendon reflexes were normal, with no pathological reflexes. The results of other neurological examinations were negative. Serum creatine kinase (269 U/l), aldolase (5.0 IU/l), aspartate aminotransferase (37 IU/l), and lactate dehydrogenase (327 IU/l) were increased. The erythrocyte sedimentation rate, leukocyte count, and C-reactive protein level were normal. Blood cell counts and the results of routine biochemical analysis were normal. Hepatitis C virus antibody was positive, but human immunodeficiency virus and human T-cell leukemia virus were negative. Various immune disorder antibodies, including anti-Jo1 and acetylcholine receptor antibodies, were negative, and serum thyroid-stimulating hormone, adrenocorticotropic hormone, parathyroid hormone and cortisol were normal. Pyruvic and lactic acids were not elevated. Electromyography of the paraspinal muscles at the levels of C5 and Th7 demonstrated reduced amplitudes (below 0.3 mV) and durations (below 5 ms) of motor unit action potentials and fibrillation potentials. All other muscles examined (biceps, triceps, adductor of thumb, sternocleidomastoideus, quadriceps, gastrocnemius, and tibialis anterior) showed no evidence of neuropathic or myopathic motor unit action potentials. A surface electromyogram showed no
854
H. Kataoka et al. / Neuromuscular Disorders 19 (2009) 853–855
Fig. 1. (Left) Before treatment with oral prednisone, the patient presented with dropped head on natural standing. (Right) After treatment with oral prednisone, the dropped head was markedly diminished on natural standing.
spontaneous activity in the left or right sternocleidomastoideus, trapezius, or paraspinal muscles at the level of C5. The results of nerve conduction studies of the four limbs were normal. Magnetic resonance imaging (MRI) of the erector muscles from the level of C1 to L5 showed abnormal high signals in the splenius from C3 to C6 on fat-suppressed and T2-weighted images (Fig. 2), but no evidence of muscular atrophy or abnormal signals in other erector muscles. Skeletal muscle MRI of both forearms and thighs revealed no evidence of atrophy or abnormal signals. Cervical MRI showed mild spondylotic changes and a narrow canal, without compression of the spinal cord, from C3 to C6, associated with dislocation of the C4 and C5 vertebrae. Biopsy of the involved splenius showed moderate variations in fiber size and necrotic and regenerating fibers, accompanied by many rimmed vacuoles and endomysial cell infiltration (Fig. 3A and B). The cell infiltrations consisted primarily of T-cells (CD8+), which was compatible with sporadic IBM. Inflammatory cells did not invade non-necrotic fibers. Immunohistochemistry for MHC-I showed sarcolemmal and internal labeling of MHC-I in some scattered muscle fibers of the endomysium. NADH-TR staining did not show fiber type predominance, but the intermyofibrillar network was clearly disorganized. No abnormal findings were detected on immunohistochemical staining for dystrophin, dysferlin, caveolin 3, or alpha, beta, gamma, and delta sarcoglycans. Electron microscopy demonstrated autophagic
vacuoles and tubulofilamentous inclusions measuring about 20 nm in width (Fig. 3C). The patient received oral prednisone 30 mg/d for 2 weeks, and neck extensor weakness improved to an MMT score of 5-strength. The dropped head had disappeared when the patient assumed a natural position (Fig. 1). Repeated skeletal muscle MRI showed that the abnormal signals of the splenius had resolved (Fig. 2). After that, she received only oral prednisone (10–20 mg/day), but the dropped head had reappeared after 12 months of follow-up. At 28 months after the onset of dropped head, the dropped head persisted, but weakness in her four limbs was not evident. Cervical skeletal muscle MRI showed mild atrophy of the erector muscles from the level of C3 to C6, but no evidence of abnormal signals. Atrophy or abnormal signals were not evident in the forearms or lower limbs by skeletal muscle MRI.
3. Discussion Muscle biopsy in our patient revealed variations in fiber size with fiber necrosis and regeneration, accompanied by many rimmed vacuoles and areas of endomysial cell infiltration. Our patient had weakness restricted to the neck extensor muscles, and further progression did not occur. In one patient with IBM who presented with weakness of the erector muscles, weakness
Fig. 2. T2-weighted MR image of the erector muscles at the C4 level showed abnormal high signal intensity before steroid treatment (left, white arrows), but the high signals had resolved after treatment (right).
H. Kataoka et al. / Neuromuscular Disorders 19 (2009) 853–855
855
Fig. 3. Histological findings of a biopsy specimen of the splenius capitis muscle from the patient. Hematoxylin and eosin staining shows increased variation in fiber size, myofiber necrosis and regeneration (white asterisk), and cellular infiltration and proliferation of endomysial connective tissue (A: scale = 40 lm). Modified Gomori-trichrome staining shows some rimmed vacuoles in muscle fibers (B: scale = 20 lm). On ultrastructural analysis, scattered in the muscle fibers are autophagic vacuoles containing cytoplasmic debris, electron dense material, and myeloid bodies (C). Tubulofilamentous nuclear inclusions are noted (D). The region in square is magnified. The diameter of the inclusions is about 20 nm. Original magnification: C, 8000; D, 25,000.
in the extremities developed subsequently [2]. In a large series of patients with IBM [6], involvement of the paraspinal muscles was absent, and involvement of the neck muscles was very rare. While, myositis can also show MRI, EMG, and clinical findings in restricted neck extensor muscles similar to those in our patient and might have caused the dropped head. Polymyositis and dermatomyositis usually involve the thigh and pelvic musculature bilaterally and symmetrically; neck involvement can occur late in the disease course. However, muscle biopsy in our patient showed no inflammatory cell infiltrates. The present diagnosis is inflammatory myopathy with rimmed vacuoles, but the patient’s general condition may be affected in the future. The reason why certain inflammatory myopathies are restricted to the neck extensor muscles remains uncertain. Frequent mechanical-stretch injury to neck extensor muscles over time associated with loss of tissue elasticity can lead to DHS [7]. In inflammatory myopathies, high blood flow rates may increase contact between T-cells and target antigens, which can lead to T-cell mediated inflammatory conditions, which
may specifically affect extensor muscles in the neck [3]. This myopathy can cause DHS in a subgroup of patients. References [1] Umapathi T, Chaudhry V, Cornblath D, Drachman D, Griffin J, Kuncl R. Head drop and camptocormia. J Neurol Neurosurg Psychiatry 2002;73:1–7. [2] Hund E, Heckl R, Goebel HH, Meinck HM. Inclusion body myositis presenting with isolated erector spinae paresis. Neurology 1995;45:993–4. [3] Kastrup A, Gdynia HJ, Nägele T, Riecker A. Dropped-head syndrome due to steroid responsive focal myositis: a case report and review of the literature. J Neurol Sci 2008;267:162–5. [4] Dominick J, Sheean G, Schleimer J, Wixom C. Response of the dropped head/bent spine syndrome to treatment with intravenous immunoglobulin. Muscle Nerve 2006;33:824–6. [5] Biran I, Cohen O, Diment J, Peyser A, Bahnof R, Steiner I. Focal, steroid responsive myositis causing dropped head syndrome. Muscle Nerve 1999;22:769–71. [6] Lotz BP, Engel AG, Nishino H, Stevens JC, Litchy WJ. Inclusion body myositis. Observations in 40 patients. Brain 1989;112:727–47. [7] Katz JS, Wolfe GI, Burns DK, Bryan WW, Fleckenstein JL, Barohn RJ. Isolated neck extensor myopathy: a common cause of dropped head syndrome. Neurology 1996;46:917–21.