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Neuromuscular Disorders 22 (2012) 987–989 www.elsevier.com/locate/nmd
Camptocormia as presenting sign in myoﬁbrillar myopathy Dimitri Renard a,⇑, Giovanni Castelnovo a, Carla Fernandez b, Andre Maues De Paula b, Sini Penttila¨ c, Tiina Suominen c, Bjarne Udd c b
a Department of Neurology, CHU Nıˆmes, Hoˆpital Caremeau, Place du Pr Debre´, 30029 Nıˆmes Cedex 4, France Department of Pathology and Neuropathology, CHU Marseille, Hoˆpital La Timone, 264, Rue Saint-Pierre, 13385 Marseille, France c Neuromuscular Research Center, Department of Neurology, Tampere University and University Hospital, Tampere, Finland
Received 30 January 2012; received in revised form 26 April 2012; accepted 6 June 2012
Abstract Camptocormia, due to paraspinal muscle weakness, is seen in several types of myopathy. Myoﬁbrillar myopathies (MFM) are histopathologically characterized by desmin-positive protein aggregates and myoﬁbrillar disintegration. Camptocormia can be seen in the late stages of the known MFM diseases. We present a case of MFM with progressive camptocormia since the age of 64, isolated for 6 years, followed later by upper and lower limb weakness. Camptocormia has never been described as the presenting clinical sign of MFM. MFM joins the growing number of myopathies potentially presenting with camptocormia. Ó 2012 Elsevier B.V. All rights reserved. Keywords: Myoﬁbrillar myopathy; Axial myopathy; Distal myopathy
2. Case report
Camptocormia (or bent spine syndrome) is an acquired postural disease characterized by forward ﬂexion of the thoraco-lumbar spine, caused by several central and peripheral nervous system diseases including Parkinson disease, dystonia, multisystem atrophy, Alzheimer disease, motor neuron disease, chronic inﬂammatory demyelinating polyneuropathy, myasthenia, and myopathy. Camptocormia associated with myopathies is most often due to paraspinal muscle weakness. Myoﬁbrillar myopathy (MFM) is histopathologically characterized by desminpositive protein aggregates and myoﬁbrillar disintegration. Trunk and neck weakness can be seen in the late stages of the known MFM diseases. Camptocormia has never been described as the presenting clinical sign of MFM. We present a case of MFM with progressive camptocormia since the age of 64, isolated for 6 years, followed later by upper and lower limb weakness.
A 78-year-old woman, without family history, presented with a progressive bent spine since the age of 64, followed by bilateral arm weakness 6 years later, and bilateral leg weakness 12 years after bent spine onset. Clinical examination showed camptocormia (without extrapyramidal signs) together with diﬀuse bilateral, proximal and distal, leg weakness (MRC scale 4/5), slight diﬀuse bilateral arm weakness, and bilateral Trendelenburg sign. Creatine kinase levels were normal. Nerve conduction studies were normal. Electromyography showed discrete ﬁbrillation potentials and positive sharp waves in proximal and distal lower limb muscles at rest, and small amplitude, brief, polyphasic action potentials, and early recruitment after muscle contraction in the proximal leg muscles. Electromyography in the paraspinal muscles showed profoundly decreased insertional activity, without ﬁbrillation potentials or positive sharp waves. Whole body muscle MRI (Fig. 1) showed normal upper limbs, profound atrophy and replacement by fatty connective tissue of the paravertebral muscles (explaining probably the decreased insertional activity on
⇑ Corresponding author. Tel.: +33 4 66 68 32 61; fax: +33 4 66 68 40 16.
E-mail address: [email protected]
(D. Renard). 0960-8966/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.nmd.2012.06.004
D. Renard et al. / Neuromuscular Disorders 22 (2012) 987–989
electromyography), and fatty degenerative changes involvement in the following muscles: all thigh muscles (except of rectus femoris, adductor longus, sartorius, gracilis, and semitendinosus), and in the lower legs severe changes in the medial head of the m. gastrocnemius, m. soleus, and to a lesser degree the m. tibialis anterior. Quadriceps muscle biopsy was performed showing myopathic features (rounding of muscle ﬁbers, pathological ﬁber size variation), abnormal myoﬁbrillar network, subsarcolemmal and sarcoplasmic protein aggregates, non-rimmed and rare rimmed vacuoles, core-like lesions, rubbed-out ﬁbers, spheroid bodies best seen in Gomori trichrome staining (Fig. 1). There were no inﬂammatory inﬁltrates, and there was no major histocompatibility complex class I upregulation. Immunohistochemical analysis showed abnormal accumulations of desmin, myotilin, and actin (Fig. 1). Cytochrome-C oxidase activity was normal, apart from decreased cytochrome-C oxidase activity seen in the corelike lesions. There was no apple-green birefringence of the Congo red material under polarized light. Menadione stain without substrate, in search for reducing body mypathy,
was normal. A pathology diagnosis of myoﬁbrillar myopathy (MFM) was made. Enzymatic blood analysis for Pompe disease was normal. In search of mutations classically described in MFM, genetic analyses for desmin (all coding sequences were screened), alphaB-crystallin (all 3 exons and intronic regions inﬂuencing mRNA splicing were analyzed), ZASP (exon 6), myotilin (exon 2), ﬁlamin C (exon 17, 18, 19, and 48), BAG3 (exon 3), and FHL-1 (exon 3 to 6) were performed. No mutations were found. Holter ECG monitoring and transthoracic echocardiography were normal. Respiratory functions tests showed a slightly decreased vital capacity (89% of the predicted value). 3. Discussion MFM are histopathologically characterized by desminpositive protein aggregates and myoﬁbrillar disintegration [1,2]. Both childhood and adult (sometimes late-adult, as in our patient) onset phenotypes are seen in MFM. Disease onset beyond the fourth-ﬁfth decade of life may suggest a myotilin-, ZASP-, or Filamin-C-related MFM. Muscle
Fig. 1. T1-weighted MRI imaging showing atrophy and replacement by adipose tissue in the paravertebral muscles (A) and the m. vastus lateralis, m. adductor brevis, m. adductor magnus, m. semimembranosus, the medial head of the m. gastrocnemius, m. soleus, and to a lesser degree the m. tibialis anterior in the lower limb (B and C). Muscle biopsy showing rounding of muscle ﬁbers, pathological ﬁber size variation, abnormal myoﬁbrillar network, subsarcolemnal and sarcoplasmic protein aggregates, rimmed and non-rimmed vacuoles, and core-like lesions on H and E staining (D). The hyaline and granular structures are Congo red positive (E). The structurally abnormal muscle ﬁbers can be observed in Gomori trichrome-stained sections (F). Immunohistochemical analysis showed ectopic accumulation of desmin (G) and myotilin (H). Arrows show some of the abnormal protein aggregates (D– H).
D. Renard et al. / Neuromuscular Disorders 22 (2012) 987–989
weakness distribution is variable, with mostly distal phenotypes in desminopathy, myotilinopathy, and ZASPopathy, whereas the muscle weakness and atrophy is more generalized with Filamin-C and BAG3 mutations. Creatine kinase levels are either normal or slightly elevated. Distinct muscle imaging patterns are seen in the diﬀerent types of myoﬁbrillar myopathies . The muscle MRI pattern found in our patient corresponded the best to the pattern found in MFM related to myotilin mutations, although no mutation was found in the myotilin gene in our patient. Cardiac and/ or respiratory involvement can be seen. Mutations in desmin, alphaB-crystallin, ZASP, myotilin, ﬁlamin-C, and BAG3 genes are responsible for about 50% of MFMs, and the rest is due to yet unidentiﬁed genes and mutations. Our patient presented with progressive camptocormia, isolated for 6 years, followed later by upper and lower limb weakness. Trunk and neck weakness can be seen in the late stages of the known MFM diseases, especially in patients with desmin and ﬁlamin-C mutations. Rigid spine during the disease course is often seen in FLNC and BAG3-related MFM. To the best of our knowledge, camptocormia has
never been described as the presenting clinical sign of MFM. In patients with camptocormia and idiopathic Parkinson disease, myoﬁbrillar disarray (stained positive for desmin) and similarities to protein surplus myopathies can be seen . The exact relationship between histological muscle abnormalities and Parkinson-associated camptocormia is unclear. Extrapyramidal signs were absent in our patient. A so far unidentiﬁed gene defect, potentially causing a predominant axial muscle involvement, may be the cause of MFM in our patient. References  Selcen D. Myoﬁbrillar myopathies. Neuromuscul Disord 2011;21: 161–71.  Selcen D, Ohno K, Engel AG. Myoﬁbrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain 2004;127: 439–51.  Fischer D, Kley RA, Strach K, et al. Distinct muscle imaging patterns in myoﬁbrillar myopathies. Neurology 2008;71:758–65.  Spuler S, Krug H, Medialdea IC, et al. Myopathy causing camptocormia in idiopathic Parkinson’s disease: a multidisciplinary approach. Mov Disord 2010;25:552–9.