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Late-onset cervicoscapular muscle atrophy and weakness after radiotherapy for Hodgkin disease: a case series
  1. A Furby1,
  2. A Béhin2,
  3. J-P Lefaucheur3,
  4. K Beauvais1,
  5. P Marcorelles4,
  6. J-M Mussini5,
  7. G Bassez3,
  8. A Créange3,
  9. B Eymard2,
  10. I Pénisson-Besnier5
  1. 1
    Unité de Neurophysiologie Clinique, Hôpital Yves Le Foll, Saint-Brieuc, France
  2. 2
    Centre de référence des maladies rares neuromusculaires, APHP, GH Pitié-Salpêtrière, Paris, France
  3. 3
    Centre de référence des maladies rares neuromusculaires, APHP, GH Henri Mondor—Albert Chenevier, Créteil, France
  4. 4
    Pôle de Biologie Pathologie, Hôpital Morvan, CHU Brest, Brest, France
  5. 5
    Centre de référence des maladies neuromusculaires Nantes-Angers, CHU d’Angers et Nantes, Angers, France
  1. Correspondence to Dr A Furby, Unité de Neurophysiologie Clinique, Hôpital Yves Le Foll, 22 027 Saint-Brieuc, France; alain.furby{at}


Patients with cervical or mediastinal Hodgkin disease (HD) classically underwent chemotherapy plus extended-field radiation therapy. We report six patients who gradually developed severe atrophy and weakness of cervical paraspinal and shoulder girdle muscles 5–30 years after mantle irradiation for HD. Although clinical presentation was uniform, including a dropped head syndrome, electrophysiological and pathological findings were rather heterogeneous. Either neurogenic or myogenic processes may be involved and sometimes combined. We discuss the pathophysiological mechanisms underlying these cervicoscapular motor complications of mantle irradiation in HD.

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The classical treatment of Hodgkin disease (HD) is based on chemotherapy plus radiation therapy (RT).1 2 3 Late neurological adverse events after extended-field RT include brachial or lumbar plexopathy4 5 and chronic progressive myelopathy.6 A few patients were found to develop severe weakness and atrophy of cervical and shoulder girdle musculature that developed several years after mantle irradiation.7 8 9 10 The clinical presentation usually includes a dropped head syndrome. The pathophysiology of this rare post-RT complication is still unclear. In this study we report detailed clinical, electrophysiological and pathological findings in six original cases sharing the same condition of late-onset cervicoscapular muscle atrophy and weakness following mantle irradiation for HD.

Case reports

The six patients had a medical history of HD (stage I to stage III) treated by chemotherapy followed by extended-field RT, including mantle irradiation, and were considered to be in complete remission. Details are given in table 1.

Table 1

Clinical characteristics, electrophysiological, imaging and pathological findings

They all were referred for weakness and atrophy of cervical paraspinal and shoulder girdle musculature. The mean delay between irradiation and first symptoms was 19.7 years (ranging from 5 to 30 years). Neck pain was reported by four patients. Patients did not complain of cramps, fasciculations, myokimia or any other abnormal spontaneous muscle activity, as well as of any sensory deficit.

Clinical examination showed severe weakness and atrophy of splenius capitis, supraspinatus, infraspinatus, trapezius, sternocleidomastoid and deltoid muscles, leading to a dropped head syndrome in four cases (fig 1). Cranial nerves were normal, and patients had neither swallowing difficulties nor dysarthria. Stretch reflexes and sensory examination were normal, except a symmetrical, distal hypoesthesia in the lower limbs (with absent achillean stretch reflexes) attributed to diabetic polyneuropathy in patient no 3.

Figure 1

(A) Clinical presentation (patient no 6): severe wasting of cervicoscapular muscles following radiation therapy for Hodgkin disease. (B, C) Deltoid muscle biopsy (patient no 2): marked fibre size variation, increased interstitial fat and connective tissue, and numerous structural changes (many whorled fibres). Haematoxylin and eosin (B) and ATPase pH 9.4 (C) staining, magnitude 200×.

Laboratory investigation was unremarkable in all patients, regarding blood-cell count, electrolyte dosage, C reactive protein, serum protein immunoelectrophoresis, thyroid function test and serologies for human immunodeficiency virus 1 and 2, and B and C hepatitis virus. The serum creatin kinase level was slightly elevated in four cases (mean = 395 IU/l). Cerebral spinal fluid examination showed elevated protein concentration (0.71 g/l) in one patient and was normal in two others. Cervical spinal magnetic resonance imaging and whole-body positron emission tomography for lymph node and metastatic examination revealed no abnormalities. Cervical computed tomography scan performed in three patients revealed diffuse muscle atrophy with fatty changes in paraspinal muscles.

In all the patients, weakness may have progressed but did not extend beyond the initially involved muscle groups over several years (1 to 9 years). Treatment by oral steroids (1 mg/kg) was administered for 3 months in one patient (no 2), without any clinical benefit.

Electrophysiological data

Nerve-conduction studies were normal in the four limbs, including no proximal conduction block or any sign of demyelinating neuropathy. A reduction in compound muscle action potential amplitude in upper trapezius muscle to spinal nerve stimulation was observed in patient no 3. Needle electromyography (EMG) showed abnormal muscle activity at rest (fibrillation potentials or complex repetitive discharges) in three patients (nos 2, 3, 4). During contraction, myopathic EMG findings (motor unit potentials (MUPs) of reduced amplitude and duration) were found in paraspinal and deltoid muscles in one patient (no 1). Two patients (nos 4, 5) showed neurogenic EMG changes in splenius capitis, upper trapezius, supraspinatus and infraspinatus muscles. A combination of myopathic MUPs with neurogenic recruitment was predominantly found in paraspinal, neck and deltoid muscles in two patients (nos 2, 3). In the last patient (no 6), needle EMG remained normal, but the examination was incomplete and did not study the most affected muscles.

Pathological studies

A biopsy of the deltoid muscle was performed in the four patients in whom this muscle was clinically affected by wasting and weakness (see table 1). Variation in muscle fibre size was mild in two patients (nos 1, 6) and more pronounced in one patient (no 2), with a combination of hypertrophic and atrophic fibres from one sample to another (fig 1). A few nuclear clumps were observed. Many fibres had a markedly disorganized architecture: some were split; others had a whorled or annular aspect. A moderate increase in the number of internalized myonuclei was found. Endomysial connective tissue was slightly increased, and some areas were infiltrated by adipocytes. Some samples showed a predominance of muscle fibres of type 1. We did not find type grouping, target/targetoid changes, necrotic fibres, inflammatory infiltrates, rods or amyloid deposits. Blood vessels were unremarkable. Immunostaining for dystrophin, sarco- and dystroglycans, dysferlin and caveolin was negative.


In 1998, Johansson et al7 first pointed out that neck and shoulder girdle muscles could present wasting and weakness in long-term HD survivors as a late complication of mantle irradiation. The following report was that of Portlock et al,8 who described histological features of nemaline myopathy in trapezius muscle of a patient who had undergone mantle irradiation for HD 16 years before. Additional cases of dropped head syndrome occurring as a late complication of mantle irradiation for HD were reported in one paper (three cases)9 and an abstract (four cases).10

The common clinical feature in all these patients, including our six patients, was a severe wasting confined to neck and shoulder girdle musculature, leading to a dropped head syndrome in most cases. It develops as a pure motor syndrome without clinical sensory manifestations, except cervical pain that preceded weakness by several months or years in some patients. Contracture of anterior cervical muscles was also described9 but not observed in our patients. Absence of paraesthesias, hypesthesia or sensory-nerve conduction abnormalities and preserved stretch reflexes can rule out the hypothesis of a plexopathy, another rare complication of mantle irradiation.4 11

The pathophysiology of cervicoscapular muscle weakness and wasting following mantle irradiation in HD could result from primary muscle damage or anterior horn or root lesions at the upper cervical level. In the present series, EMG changes were myopathic in one patient and neurogenic in two patients, and included a combination of myopathic MUPs with neurogenic recruitment in two others. In the literature, both myopathic and neurogenic EMG alterations have also been reported.9 Regarding histopathological studies, the abnormalities were non-specific in the four patients in whom we performed a muscle biopsy, but they were more in line with predominant non-inflammatory myopathic changes. Such a finding has been previously reported,10 as well as the presence of rod/nemaline bodies8 or features of muscle denervation.9

Both myopathic and neurogenic processes may underlie the pathophysiological changes, because cervicoscapular muscles are located within the field of mantle irradiation as well as upper cervical anterior horns and roots. In addition, the potential neuromuscular toxicity of chemotherapeutic drugs could play a sensitisation role. However, myopathic and neurogenic processes may not be equally involved in all patients and territories. Following our observations, myopathic features seemed to be predominant regarding histopathological findings in deltoid muscles, while definite neurogenic signs could be found in the needle EMG examination of neck and paraspinal muscles. Nevertheless, myopathic alterations were clearly predominant in three patients of this series.

Irradiation has been considered to cause relatively little or no direct damage to mature muscle fibres, and in fact myositis is an infrequently reported adverse effect of RT.12 However, high radiation doses are known to dramatically alter the proliferation of muscle precursor cells and were used in experimental animal models to inhibit spontaneous muscle regeneration.13 Fajardo and Berthrong14 hypothesized that radiation could induce primarily vascular lesions due to a high susceptibility to radiation of capillaries and vessels. These lesions may result from an imbalance in the cross-talk between endothelial cells and vascular smooth muscle cells.15 A secondary increase in collagen content and a proliferation of fibrous tissue may occur in the irradiated tissue,16 leading to progressive deterioration over several years following RT. These processes are delayed, evolving many years after RT completion, and they are generally dose- and time-dependent.

In conclusion, clinicians should be aware that weakness and wasting can occur in neck and shoulder girdle musculature of long-term HD survivors who had previously undergone mantle irradiation. Whatever the underlying pathophysiology, the lesions appear to be irreversible like other delayed complications of RT. This observation supports the current development of involved-field RT protocols based on limited rather than extended fields of irradiation to reduce the risk of late complications.


The authors are grateful to P Bouche, GH Pitié-Salpêtrière, Paris, and G Taurin, CH Saint-Malo, for their collaboration and support in patient care.



  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and Peer review Not commissioned; externally peer reviewed.