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A Japanese case of steroid responsive myopathy with deficient chondroitin sulphate
  1. I Yabe1,
  2. S Kikuchi1,
  3. T Higashi1,
  4. K Tashiro1,
  5. Y Maruo2
  1. 1Department of Neurology, Hokkaido University School of Medicine, N-15 W-7, Kita-ku, Sapporo 060-8638, Japan
  2. 2Department of Neurology, Hakodate City Hospital, Hakodate, Japan
  1. Correspondence to:
 Dr Yabe;

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In 1998, Al-Lozi et al described a case of steroid responsive myopathy with deficient chondroitin sulphate C that had not been reported before.1 The patient developed diffuse bulbar and systemic weakness with respiratory failure. While muscle biopsy showed only a moderate degree of type 2 atrophy with one small perimysial, perivascular mononuclear cell infiltration, immunocytochemistry showed an absence of chondroitin sulphate C in the endomysium. Prednisone treatment resulted in a marked increase in muscle strength. Here we report another case of this interesting and treatable muscle disorder.

Case history

A Japanese woman first developed neck muscle weakness, dysphasia, and weight loss at the age of 42 years. She was diagnosed as having anorexia nervosa and was placed on antidepressive drug treatment. Her symptoms worsened and after a few months she developed weakness in all of her limbs, sluggish speech, and diplopia, and began having difficulty with breathing. She presented in our outpatient clinic in 1993 at the age of 43.

Her personal and family histories were negative for neuromuscular disorders. On physical examination, she was very thin (height 162 cm; weight 32 kg), and her temperature was 38.1°C. Coarse crackles were heard in the right lower lung. Neurological examination revealed dysarthria, dysphasia, bilateral ptosis, limitation of extraocular movements in all directions, proximal muscle weakness of all four limbs, and generalised hyporeflexia. Her muscle tone, sensory perception, and autonomic system were normal, as was her cognitive function.

Laboratory tests showed signs of inflammation (white blood count 9000/μ1, C reactive protein 3.2 mg/dl), considered to be the result of mild aspiration pneumonia in the right lower lung on chest x ray. There was also hypoproteinaemia. Blood gase analysis revealed hypoxia, with a Pao2 of 8.05 kPa, a Paco2 of 9.27 kPa, and a blood pH of 7.392. Other blood constituents were normal, including creatinine kinase, aldolase, antiacetylcholine receptor antibody, antinuclear antibody, lactic acid, and pyruvic acid. Urinalysis, ECG, and cerebrospinal fluid examination were also normal, as was brain magnetic resonance imaging.

Electromyography (EMG) showed myogenic discharges in both biceps brachii, the left rectus femoris, and in both sternocleidomastoid muscles. Motor and sensory nerve velocities were normal in the median, ulnar, tibial, peroneal, and sural nerves. Repetitive stimulation tests of the facial and deltoid muscles gave normal results. A tensilon test was negative.

Because she was clinically diagnosed as having atypical oculopharyngeal myopathy with respiratory failure, a biopsy was performed on the right rectus femoris muscle. On histochemical examination, a moderate degree of type 2 atrophy was identified (fig 1A). Immunohistochemical investigation using antibodies to CD3, CD4, CD8, CD68, and CD22 (Dako Denmark; catalogue Nos 054, 105, 036, 044, and 093) failed to show the presence of infiltrating inflammatory cells (data not shown).2 At this time, the origin of the patient's disorder remained undetermined.

Figure 1

(A) Muscle biopsy from our patient showing a predominant type 2 fibre atrophy (adenosine triphosphatase 10.4 staining, ×50). (B) Immunohistochemical staining of muscle obtained from our patient and (C) from disease control subjects, using a chondroitin sulphate specific antibody (×66). Chondroitin sulphate staining was absent from the muscle of our patient.

The patient was given prednisone orally in a dose of 60 mg/day and her symptoms markedly improved. By day 7, the diplopia, dysphagia, and dyspnoea had resolved. After four months, she was discharged with no remaining neurological deficit. Her prednisone dosage was gradually reduced and eight years later, at the time of writing, she was taking a maintenance dose of 20 mg every other day and showed no neurological deterioration.

Because the clinical features of steroid responsive myopathy with deficient chondroitin sulphate C—first reported in 19981 —were similar to those in our case, we carried out an immunohistochemical study using a monoclonal antibody to chondroitin sulphate (Sigma-Aldrich USA; catalogue No C8035) on frozen muscle samples obtained in 1993 before the patient was started on prednisone. The results showed that there was no binding of antibody to the endomysium or small vessels in the patient's muscle (fig 1B). In diseased control muscles, diagnosed as motor neurone disease in 1993, chondroitin sulphate staining was demonstrable (fig lC).


Our patient showed the following clinical features: progressive bulbar symptoms, extraocular movement limitation, and proximal muscle weakness with respiratory failure; steroid responsiveness; and type 2 muscle fibre atrophy with no staining of chondroitin sulphate on histochemical examination. Apart from the limitation of her extraocular movements, the EMG results and the absence of an inflammatory infiltrate on histochemical examination, all other clinical features were markedly similar to those seen in the only other reported case.1 As the antibody used in our immunohistochemical analysis could not discriminate between subtypes of chondroitin sulphate, we were unable to conclude that our patient's deficient subtype was definitely type C, though the clinical similarities with the other reported case suggest that this was the case.

Type 2 muscle fibre atrophy has been reported in the muscles of malnourished patients.3 Our patient was certainly malnourished as a result of severe bulbar involvement. The other patient with steroid responsive myopathy was similarly reported to have been malnourished, for a period of 18 months. Thus it is likely that the type 2 fibre atrophy shown in both these patients was caused by malnutrition.

Chondroitin sulphates are major constituents of the extracellular matrix of skeletal muscle and play an important role in binding cytokines as well as in cellular adhesion, differentiation, and signal transduction.4 Thus their disruption in muscle is thought to be involved in the pathogenesis of disease. Al-Lozi et al suggested that myopathy might be caused by a deficit in chondroitin sulphate C developing as a result of immune mediated mechanisms.1 In our case, there was dramatic improvement with steroid treatment, further supporting a role of the immune system in the disease pathogenesis.

In conclusion, we presented a case of steroid responsive myopathy with deficient chondroitin sulphate. This condition should be considered in cases of atypical oculopharyngeal myopathy of unknown origin.