G.P.105

Main symptoms at onset and chief complaints at the first visit to clinic of

myotonic dystrophy

K. Ogata 1, M. Suzuki 1, K. Yatabe 1, T. Shigeyama 2, Y. Honma 1,

K. Momma 1, A. Noju 1, M. Takata 1, Y. Tanaka 1, K. Nagata 1,

I. Nonaka 1, T. Tamura 1, M. Kawai 1

1 NHO Higashisaitama Hospital, Neurology, Hasuda, Saitama,

Japan; 2 NHO Higashisaitama Hospital, Cardiology, Hasuda, Saitama,

Japan

Myotonic dystrophy (DM) is an autosomal dominant disorder with

dysfunction of multiple systems. Concurrent features of skeletal mus-

cles, myotonia and weakness, do not make difficulties with DM patients

in early and mild stage, and progress slowly. Consequently, the diagno-

sis of DM in the early stage is difficult and tends to delay. We analyzed

main symptoms at onset and chief complaints at the first visit to clinic

from the medical records of 67 our patients with DM (41 males, 26

females). Mean age of their onset was 27.2 ± 14.1. The main symptoms

at onset were; weakness, 40; myotonia, 17; mental retardation, 8; dys-

arthria, 1; lumbago, 1. Mean interval from onset to their first visit to

neurological clinics about DM was 11.6 ± 9.9 years. The chief com-

plaints at the first visit to clinics were; weakness, 44; myotonia, 7; dys-

arthria, 2; lumbago, 2; genetic counseling, 2; apathy, 1; syncope, 1; no

complaint, 8. Among 17 patients onset with myotonia, only 7 were with

also myotonia as the chief complaint at the first visit to clinic. Among

40 patients onset with weakness, 33 were with weakness as the chief

complaint at the first visit to clinic. Myotonia is a characteristic and

important sign for DM, which provides early diagnosis. In contrast,

myotonia is less likely to be a reason for consultation to medical doc-

tor, suggesting that patients with DM are suffering more with weakness

than with myotonia.

http://dx.doi:10.1016/j.nmd.2012.06.318

G.P.106

Immunohistochemical study of cricopharyngeal muscle in oculopharyngeal

muscular dystrophy

T. Gidaro 1, S. Perie 2, M. Lesnik 3, E. Negroni 3, M. Oloko 3, J. Lacau st

Guily 2, G. Butler-Browne 3, V. Mouly 3, C. Trollet 3

1 UPMC Universite Paris 6, UM76, Institut de Myologie, INSERM U974,

Paris, France; 2 Service d’Oto-Rhino-Laryngologie et de Chirurgie Cervico-

Faciale, Paris, France; 3 Therapie des maladies du muscle strie/ Institut de

Myologie, UM76 – UPMC Univ. Paris 6, U974 – Inserm, UMR7215 –

CNRS, Paris, France

Several studies have reported abnormalities in muscle histology of cri-

copharyngeal muscle (CPM) from healthy donors. However, very little is

known concerning the morphological structure of this muscle that,

together with the elevator eyelid muscle, represents the main muscular tar-

gets of oculopharyngeal muscular dystrophy (OPMD). OPMD is a late

onset autosomal dominant inherited dystrophy due to an expansion of

GCG repeats in the coding region of the ubiquitously expressed PABPN1

gene. In OPMD patients, progressive involvement of these muscles leads

to dysphagia and ptosis. In this study, CPM biopsies from seven OPMD

patients and five healthy individuals were investigated by histological and

histochemical approaches as well as by quantitative RT-PCR analysis.

Surprisingly, histological features were similar between OPMD patients

and control subjects without any correlation with age: in addition to the

extensive fibro-connective substitution (30–40%), all CPM showed a high

variability in muscle fibre size, rimmed vacuoles, internalized nuclei, ’rag-

ged red’ fibres and split fibres. In CPM, a higher number of satellite cells

were observed as compared to other muscle, with a significant difference

between control and OPMD (7% versus 12% respectively), further con-

firmed by increased Pax7 mRNA levels. To further evaluate the regenera-

tive capacity of these satellite cells, OPMD and control cells were

transplanted into cryodamaged tibialis anterior muscle of immunodefi-

cient mice. This study will help us to understand the defects in muscle

fibres regeneration in OPMD. Analyses on CPM are now being extended

to a less affected muscle, the sternocleidomastoideus muscle (SCM) from

OPMD and healthy individuals to improve our understanding of the path-

ophysiology of OPMD.

http://dx.doi:10.1016/j.nmd.2012.06.319

G.P.107

OPMD or OPDM: How to differentiate?

M.X. Wang 1, S. Brammah 2, S. Flanagan 1, S. Jahdhami 1,

R. Pamphlett 1, M.E. Buckland 1

1 University of Sydney & Royal Prince Alfred Hospital, Clinical Neurosci-

ences, Sydney, Australia; 2 Concord Hospital, Electron Microscopy Unit,

Sydney, Australia

Oculopharyngeal muscular dystrophy (OPMD) is a late onset muscu-

lar dystrophy (2nd–6th decades) with an expansion of GCG repeats in

exon 1 of PABPN1. Oculopharyngodistal myopathy (OPDM) is also an

adult-onset hereditary muscle disease with putative autosomal dominant

and autosomal recessive inheritance. The genetic defect in OPDM remains

unknown. OPDM and OPMD overlap clinically and histopathologically,

since both disorders have a similar distribution of weakness, rimmed vac-

uoles and mitochondrial disarray. We studied 9 patients with oculopha-

ryngeal weakness and rimmed vacuoles to find a practical approach to

differentiate OPMD and OPDM. All patients (mean age 63 y, range 21–

79 y) had ptosis, dysphagia and limb muscle weakness. Muscle biopsies

showed rimmed vacuoles, dystrophic features and mitochondrial disarray.

Five cases had HLA-1 immunostaining and electron microscopy (EM)

performed. None of the patients had diffuse HLA-1 upregulation in the

sarcolemma. On EM 8.5 nm intranuclear filaments (OPMD filaments)

were found in three patients and 16–18 nm filaments (IBM filaments) in

the other 2. Genetic testing confirmed PABPN1 mutations in the three

patients with OPMD filaments. The other two patients were diagnosed

as OPDM. In summary, HLA-1 staining is helpful in differentiating

sporadic IBM from OPMD or OPDM since it is absent in the latter two

conditions. Persistent EM examination looking for 8.5 nm intranuclear

filaments can aid the diagnosis of OPMD. The diagnosis of

OPDM requires clinical, histopathological and genetic analysis to exclude

OPMD.

http://dx.doi:10.1016/j.nmd.2012.06.320

G.P.108

Sarcomeric dysfunction contributes to muscle weakness in facioscapulohu-

meral muscular dystrophy

S. Lassche 1, G.J.M. Stienen 2, T.C. Irving 3, S.M. van der Maarel 4,

G.W. Padberg 1, H. Granzier 5, C.A.C. Ottenheijm 2, B.G.M. van

Engelen 1

1 Radboud University Nijmegen Medical Centre, Neurology, Nijmegen,

Netherlands; 2 VU University Medical Center, Physiology, Amsterdam,

Netherlands; 3 Illinois Institute of Technology, Department of Biological,

Chemical and Physical Sciences, Chicago, United States; 4 LUMC, Genet-

ics, Leiden, Netherlands; 5 University of Arizona, Physiology, Tucson,

United States

The expression of sarcomeric proteins is impaired in facioscapulohu-

meral muscular dystrophy (FSHD), a common hereditary myopathy char-

acterized by muscle weakness. In addition, overexpression of DUX4, the

900 Abstracts / Neuromuscular Disorders 22 (2012) 804–908