CASE REPORT
A 60-year-old female with no personal or family history of myopathy started in November/2014 to feel cervical pain in the shoulder girdle and upper limbs. Over three months, she developed muscle weakness resulting in proximal myopathy with drop-head and tetraparesis of proximal predominance. In July/2015, there was worsening of symptoms with dysphonia (ocular and tongue movements were regular) and unintentional weight loss (10 kg in 8 months). She also presented a myopathic gate with hyperlordosis, posterior pelvic tilt and bilateral winged scapula with hypotrophy of proximal muscles at the limbs without fasciculations (Figure 1A). Tendon reflexes and sensory perception were preserved. No respiratory involvement was evident, and her spirometry was normal. Human immunodeficiency virus and hepatitis serologies, autoimmune and active neoplastic screenings were negative. Normal levels of myoglobin, aldolase, creatine phosphokinase, lactate dehydrogenase and thyroid hormones were found. No abnormalities in echocardiogram or electrocardiogram were noted. Serum protein electrophoresis revealed an M-protein IgG lambda spike of 12 g/L with normal immunoglobulin levels, normal free light chain ratio, negative urinary immunofixation and no bone marrow plasmacytosis. Anemia, hypercalcemia, renal dysfunction, and bone attainment were absent. Amyloid substance exploration was negative. Therefore, a monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Needle electromyography (EMG) showed myopathic pattern of the action potentials of the motor unity in all muscles explored, especially severe in cervical and the scapular girdle. However, there were no slow waves and fibrillation at rest. Left biceps brachii muscle biopsy demonstrated marked variation in fiber size with many atrophic angulated fibers containing numerous reddish granules representing positive rods in Gomori trichrome and immunohistochemistry for myotilin. The atrophic fibers were mainly of type 1; there was no necrosis, fibrosis or inflammatory infiltrate (Figure 2). The association of SLOMN and monoclonal gammopathy was assumed as a monoclonal gammopathy of neurological significance (MGNS) rather than an unknown significance.
In December/2015, collection of peripheral hematopoietic precursors after mobilization with granulocyte colony-stimulating factor (G-CSF) was performed obtaining 2.02x10^6 CD34+cells/kg. In January/2016, was submitted to ASCT after conditioning with melphalan 140 mg/m2. Neuromuscular deficits got worse in the acute phase after ASCT, with stabilization at eight months of follow-up. Due to the persistence of the monoclonal gammopathy at day 100 evaluation after ASCT, treatment with lenalidomide plus dexamethasone was started in September/2016. The patient recovered from general status, but after the fourth cycle, this trend was reversed occurring weight lost. Neuromuscular dysfunction with kyphotic posture remained stable until May/2017. By that time asthenia got worse accompanied by weight lost, myopathy aggravation with de novo hyperreflexia and respiratory insufficiency. With this evolution, lenalidomide was discontinued on the 9th cycle. Noninvasive ventilation (NIV) and third-line treatment targeting the plasma cell clone with cyclophosphamide, bortezomib and dexamethasone (CyBorDex) were started in July/2017 for a total of eight cycles until January/2018. For the first time, after four cycles of CyBorDex, serum immunofixation got negative. Patient strength significantly improved, regaining the capacity of head elevation (Figure 1B), greater autonomy in daily life activities at home and a weight recovery of 12 kilograms over the CyBorDex treatment (Figure 3) again. The patient kept stable since the start of this treatment, reaching a weight of 54.7 kilograms and achieved the independence of nocturn NIV. The monoclonal gammopathy remains in complete remission three years after finishing treatments.