Muscle Bound or Unbound?

Neuro-ophthalmic examination disclosed left upper lid ptosis that worsened with prolonged upgaze. Ocular ductions were brisk, full, and smooth without nystagmus. There was a left hypertropia that varied with gaze position. Our diagnosis is rippling muscle disease (RMD) and myasthenia gravis (MG). First described in 19751 , RMD is characterized by muscle stiffness, cramping, and percussion-induced muscle contractions that are electrically silent in the genetic form with mutations in caveolin-3 (CAV3) 2 . Our patient's features suggested acquired RMD, an autoimmune disorder with antibodies against titin, a sarcomere support protein. MG also has anti-titin antibodies and shares some overlapping immunoreactive sequences with RMD 3 , but was not associated with RMD until 1996.4 In 1995, Kosmorsky et al 5 reported (at this meeting and in the JNO) a patient who had muscle rippling and intermittent esotropia attributed to muscle cramping because the EMG did not show a decremental response. Muscle biopsy showed findings consistent with RMD. Because MG was not suspected, neither acetylcholine receptor antibody (ARAB) testing nor single-fiber EMG was done. Three years later, that patient was examined elsewhere by Ansevin et al 4 , who reported florid ocular and systemic myasthenic signs and only mild muscle rippling, a positive ARAB, EMG electrodecrement, and clinical improvement following edrophonium chloride testing. Repeat muscle biopsy showed the findings described by Kosmorsky and later by Schoser et al6 . Review of those reports led our pathologist to consider the findings distinct from either MG or genetic RMD. Thirteen cases of coexisting RMD and MG have since been reported2,6 , but only one has had RMD symptoms preceding MG, and none has had elevated ARAB in the absence of MG symptoms, as our patient had. Treatment of our patient with pyridostigmine 240mg/day worsened the rippling and cramping, a previously reported phenomenon6 . Prednisone 20 mg/day rapidly improved all manifestations.