A Woman With Focal Spontaneous Muscle Movements

A 42-year-old right-handed, Black woman came complaining that her leg muscles got tight and “moved on their own” for about 4–5 months prior to presentation and had gotten progressively worse. The symptoms were more prominent in the thighs and buttocks but occasionally involved the anterior abdominal wall and chest. She had spasms with swelling which produced discomfort and pain. She denied numbness, paresthesias, or other neurological complaints. Exercise might make the movements appear more often.

Past medical history was remarkable for “benign cysts” in the axilla and a Bartholin cyst. She had been on a muscle relaxer without benefit. She did not smoke, drink alcohol, or use recreational drugs. Family history was negative.

General physical examination was normal, but she was observed to have spontaneous waveform-like contractions in the thigh muscles ( Fig. 112-1 ). She could reproduce these contractions by massaging and pressing the thighs. There was no rash. She had normal mentation and cranial nerves, without ptosis, fatigue, diplopia, or muscle weakness and wasting. Reflexes were slightly brisk but symmetrical, and plantar responses were flexor. Coordination and sensory examinations were normal. There was no grip or percussion myotonia, but there was mild myoedema. The rest of the examination was unremarkable.

What is the Differential Diagnosis?

This patient appears to have a syndrome of neuromuscular irritability. There was no clinical myotonia to indicate a myotonic syndrome. The contractions were focal and not persistent or prominent in the trunk to suggest stiff-person syndrome. These appeared and disappeared spontaneously and rapidly and were not the characteristic contractions seen in the glycogenesis. The movements resembled cramps but there were no fasciculations present as in the cramp-fasciculation syndrome. Issacs syndrome is another consideration because of the spasms and focal contractions.

Comprehensive metabolic and thyroid-stimulating hormones were normal. HIV was nonreactive. FANA titers were elevated at 1:640 speckles, rheumatoid factor was 194 IU/mL (normal, <14 IU/mL). Serum creatine kinase was 1150 IU/L (normal, 0–165 IU/L). Erythrocyte sedimentation rate was 84 mm/h (normal, <30 mm/h). Complete blood count showed normal white blood cells, but her hematocrit was 22%–84%; hemoglobin was 6.6 g/dL.

A CAT scan of the chest was normal. Stool for occult guaiac was negative.

An EMG Test was Performed

Nerve conduction studies were normal, and on EMG there was no evidence of myokymia, myotonia, or other abnormal electrical discharge at rest. The motor units were normal and did not fire spontaneously. The waveform contractions observed clinically were not associated with electrical action potentials.

It was concluded that she had rippling muscle disease (RMD).

A muscle biopsy showed some myofiber necrosis with phagocytosis and mild interstitial inflammatory infiltrates with patchy decreased staining for caveolin ( Fig. 112-2 ).

Discussion

This patient has RMD, a condition that manifests with electrically silent wave-like contractions, and although she had no clinical evidence of lupus erythematosus, her lupus tests were positive. The erythrocyte sedimentation rate was also elevated, but her anemia could have contributed to this.

She was treated with metaxalone with minimal improvement; the addition of dantrolene also helped, and later prednisone 30 mg/day caused marked improvement. She was also found to have iron-deficiency anemia, believed to be from heavy menses, and was treated with iron replacement.

RMD is characterized by muscle hyperexcitability with spasms and contractions which can be induced by muscle stitching, pressure, and percussion. The contractions are silent.

RMD could be hereditary or acquired. The disease is named for the self-propagation, rippling, or rolling of muscle with a velocity of about 0.6 m/s. Additional clinical features are myoedema or localized mounding of the muscles after percussion. There is usually no associated weakness, although distal weakness can be seen rarely.

As in this patient, acquired RMD may be immune-mediated, and some patients have myasthenia gravis. They could also have antibodies against striated muscle and potassium voltage-gated muscle channels. There are cases with hypothyroidism.

RMD was originally described by Torbergsen in 1975 and Ricker in 1989 who first used the descriptive name. The classic hereditary form is autosomal-dominant with variable presentations as associated with mutations of the caveolin gene linked to chromosome C1q41; some cases have cardiomyopathy. This genetic defect has been excluded in some patients. A caveolin-3 mutation on chromosome 3p25 has been associated with RMD and is allelic to limb-girdle dystrophy 1C. A severe autosomal-recessive RMD has also been described.

The exact cause of muscle rippling is unknown, but the region of the C1q42 contains important proteins that participate in excitation–contraction coupling, including α-actinin, α-actin troponin I, and cardiac ryanodine receptor. The pathogenesis in those with caveolin mutations may be explained by the important role of caveolin in the structural integrity of the sarcoplasm and signal translation. To explain the mechanism of rippling, in vitro studies show after-contractions with increased sarcolemma excitability due to a delayed released of calcium by the sarcoplasmic reticulum. Alterations of the tubular system have also been observed. Recently, Lamb suggested that rippling is caused by action potential in the tubular system that does not excite the sarcolemma. Those are not detectable by electromyography and thus are considered to be “silent.”

A focal-decreased staining of caveolin has been demonstrated in acquired RMD, likely caused by antibodies against the sarcolemma.

There is no cure for RMD, but some patients respond to muscle relaxants, and those with the acquired form might also respond to immunotherapy.

Summary

This patient had wave-like muscle contractions that were electrically silent; she was diagnosed as having RMD. In her case, this was likely autoimmune and responded to dantrolene and steroids.

Important Points

•

Spontaneous, electrically silent muscle contractures that are persistent for minutes occur in metabolic myopathy. In RMD, they have wave-like characteristic but appear and disappear promptly.
•

RMD can be hereditary from mutations of C1q41 and the CAV 3 gene in chromosome 3p25 but can have an autoimmune etiology, sometimes associated with myasthenia gravis and hypothyroidism.
•

The disease responds to dantrolene, and steroids in the acquired form.